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Real-world effectiveness of clozapine for borderline personality disorder: Results from a 2-year mirror-image study menstruation gas cheap 25 mg kyliformon with mastercard. A review of the use of clozapine levels to guide treatment and determine cause of death. Clozapine and "high-dose" olanzapine in refractory early-onset schizophrenia: A 12-week randomized and double-blind comparison. A randomized, double-blind, placebo- controlled trial of metformin treatment of weight gain associated with initiation of atypical antipsychotic therapy in children and adolescents. Subsequently, self-report, parent-report, and observational measures have been developed for children and adolescents. In Section 4, we introduce the notion of sensitivity groups based on empirical findings suggesting the existence of three sensitivity categories. Traditionally, the most extensively studied phenotypical markers of heightened sensitivity have been negative emotionality and difficult temperament, and thus sensitivity has been considered synonymous with vulnerability. According to the Diathesis-stress model (Monroe & Simons, 1991), individuals scoring high on negative emotionality and/or difficult temperament show an increased susceptibility to negative environments with a dual-risk effect, such that the risk for negative outcomes is higher in the presence of risky conditions at both the individual (negative emotionality/difficult temperament) and the environmental. Conversely, those scoring low on these traits are resilient in the face of adversities, but they do not benefit more from positive environments: they are overall not sensitive to environmental influences. The inclusion of negative emotionality, particularly in developmental studies, as a candidate phenotypic marker of an increased sensitivity to stimuli has been most likely the heritage of a developmental psychology approach that was largely interested in understanding the mechanisms underlying maladaptive outcomes, and thus predominantly focused on the adverse effects of problems and disorders (Rutter & Sroufe, 2000). As soon as the focus of studies started to include positive environments and positive outcomes, research evidence proved negative emotionality in infants to be a marker of sensitivity to positive environments as well. As such, children with a highly negative temperament showed evidence of outperforming their peers scoring low on this trait in terms of positive developmental outcomes when exposed to supportive environmental conditions, such as positive parenting (Belsky & Pluess, 2009; Kim & Kochanska, 2012). The bright side of these models is captured by the more recent Vantage Sensitivity model (Pluess & Belsky, 2013), which postulates that some individuals are particularly susceptible to exceptionally positive environments, while not necessarily being more sensitive to negative stimuli. Though these theories differ from one another in predicting the type of response to the environment (and for other theoretical aspects described more in details in Pluess, 2015), these models agree on the notion that only a minority of the population presents an increased sensitivity to environmental and internal stimuli, while the majority is low in sensitivity. For this reason, they have been considered part of the broader metaframework of environmental sensitivity (Pluess, 2015). Among theories of environmental sensitivity, there is also the term "sensory processing sensitivity" (Aron et al. Several theories and dimensions of temperament and personality have been proposed to capture individual differences, and what characterizes these different theories is that almost all distinguish between more and less reactive (responsive) individuals. This depth of processing is associated with an increased sensitivity to external and internal stimuli. As environmental events are perceived and processed more deeply by highly sensitive individuals, these individuals are also more affected for better and for worse, as shown by measures of outcomes and adjustment as discussed in Chapter 4 (see, for example, the perception of stress at work in highly sensitive adults in Evers, Rasche, & Schabracq, 2008, and the positive response to intervention programs in Pluess & Boniwell, 2015 and Nocentini et al. Together with inhibition, negative emotionality has been another widely investigated marker of increased sensitivity to the environment, particularly in children (for a metaanalysis, see Slagt, Dubas, Dekovic, & van Aken, 2016). Because negative emotionality involves the expression of negative emotions in response to negative environmental conditions (Rothbart & Bates, 2006), it may appear intuitive that displays of negative emotionality may serve as a marker of high sensitivity, particularly in adverse environments. Empirical evidence showed that associations between higher home-crowding and perceptions of home chaos were significant only for highly sensitive mothers (Wachs, 2013). However, high negative emotionality has been reported as a marker of increased sensitivity to positive stimuli too (for a metaanalysis, see Slagt et al. As such, researchers have described the trait more generally as "reactivity," "responsiveness," and high sensitivity with corresponding theories about differential susceptibility (Belsky & Pluess, 2009; Belsky et al. According to these theories of environmental sensitivity, negative emotional reactions reflect an increased sensitivity of the central nervous system to even mildly negative stimuli, which more broadly is associated with both positive and negative events being registered more easily (Pluess & Belsky, 2010). However, recent empirical evidence pointed out that negative emotionality is a strong marker of an increased sensitivity to the environment in infancy and toddlerhood, but does not seem to capture sensitivity toward both positive and negative environments at an older age (Slagt et al. From around preschool years, children scoring high on this trait have been reported to be rather more susceptible to the influence of negative environments only. One candidate explanation is that if raised by a sensitive and responsive parent, a child who in early infancy was high in negative emotionality (and highly sensitive) may express a decrease in his/her negative emotional reactions. Partly, this may be due to lower frequency of exposure to negative stimuli, due to greater supporting, nurturing, and positive environmental experiences. Alternatively, and perhaps correspondingly, in such types of supportive and positive environments, the child may have learned to better regulate emotions, as a result of positive parenting practices (Karreman,Van Tuijl, van Aken, & Dekovi, 2006). In fact, there is evidence with adult brain imaging studies showing that when exposed to positive or negative pictures, highly sensitive individuals reporting positive childhood environments, confer stronger brain activity in regions that are involved in self-regulation (Acevedo, Jagiellowicz, Aron, Marhenke, & Aron, 2017). For example, highly sensitive individuals have been proposed to be more sensitive to the arts (Bridges & Schendan, 2019). Items composing this scale were identified through a series of interviews with persons self-identified as "highly sensitive" in order to gain a better understanding of what sensitivity is. As such, this variety of items (correlating with each other) was capturing a broader phenomenon than being sensitive to sensory stimuli only, or being shy or inhibited. Proposed in 2002 in the "Highly Sensitive Child" book by Elaine Aron in a "yes" vs "no" answer format, it has been only recently empirically tested for its association with a set of candidate symptoms, and for its factorial structure, in a study featuring a group of 253 parents based in Flanders, Belgium. Association with symptom variables showed that children with more problems in daily functioning. This scale is also available in a parent-report format for investigating 24 the highly sensitive brain Table 1 the Highly Sensitive Child scale. This makes me perform worse than normal a Aesthetic Sensitivity Low Sensory Thresholds Aesthetic Sensitivity Ease of Excitation Aesthetic Sensitivity Ease of Excitation Low Sensory Thresholds Ease of Excitation Ease of Excitation Aesthetic Sensitivity Low Sensory Thresholds Ease of Excitation Factors as reported in Pluess et al. More specifically, depression scores, assessed using the widely known Center for Epidemiologic Studies Depression Scale (Radloff, 1977), continued to decrease significantly among highly sensitive females, even 6 and 12 months after completing the intervention. That is, highly sensitive individuals were most susceptible to the influence of positive stimuli, outperforming their low-sensitive peers (Pluess & Belsky, 2013). This sensitivity response to exceptionally positive stimuli has been recently reported also in a large scale randomized-controlled trial aimed at testing a school-based antibullying intervention in an Italian-based population (Nocentini et al. The study involved 2042 nine- to tenyear-old childrenrandomly divided into two groups: the intervention group and the control (no-intervention) group. Results showed that significant intervention effects on victimization and internalizing symptoms were driven by gender and sensitivity. Specifically, for highly sensitive children, a greater number of childhood family adversities was associated with lower levels of physical comfort and less social competence. On the contrary, when sensitivity was low, the effect of the environment on outcomes was significantly lower or even not significant, depending on the variable investigated. The study involved 264 Dutch kindergartners followed for three waves, spaced seven months apart. Partial measurement invariance has been supported across United Kingdom and Dutch samples (Weyn et al. My child gets annoyed when people try to get him/her to do too many things at once 7. This makes my child perform worse than normal a Aesthetic Sensitivity Low Sensory Thresholds Aesthetic Sensitivity Ease of Excitation Aesthetic Sensitivity Ease of Excitation Low Sensory Thresholds Ease of Excitation Ease of Excitation Aesthetic Sensitivity Low Sensory Thresholds Ease of Excitation Factors as reported in Slagt et al. One is that they require very limited administration time, allowing them to be completed along with other measures. Preference for (and commitment to drawing) beautiful circles As reported in Lionetti, Aron, et al. Data based on a sample of 292 children in the United States (Lionetti, Aron, et al. The measure has been shown to capture sensitivity to both positive and negative quality parenting. Children scoring high on the sensitivity summary score, being more vulnerable to the effects of negative parenting (and, specifically, high levels of permissive parenting) experienced at age 3, showed increased externalizing behavioral problems at age 3 and internalizing behavioral problems at ages 3 and 6. Also, the same children showed the highest levels of social competence in response to positive parenting (high levels of authoritative parenting), and results remained stable after controlling for negative affect (Lionetti, Aron, et al. Overall, these research findings suggest that this newly developed observational measure is able to capture an increased sensitivity to stimuli and provides an opportunity for exploring sensitivity in young children. Combined with parentreport scales, it allows a multiinformant and multiassessment investigation of sensitivity in young children. Though sensitivity is theoretically considered to be a trait that is largely genetically determined, according to some developmental theories (Ellis & Boyce, 2008) the environment might play a role in shaping individual differences in sensitivity. Assessing the degree of change and stability of sensitivity across human (and perhaps even animal) development would allow us to more extensively test this hypothesis. Finally, for assessing sensitivity among children in the school context, currently a teacher-report and an observational measure for primary school children are under development and validation in an ongoing 2-year longitudinal study (Pluess & Lionetti, 2018).

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Omega-3 fatty acids contained in fish oil can protect blood vessels as well as reduce inflammation of the brain (Luchsinger menstrual cup 25 mg kyliformon with visa, Tang, Shea & Mayeux, 2002). In addition, high intake of total fat, saturated fat, and cholesterol increased the onset of dementia, whereas risk of dementia decreased in the group that consumed a lot of fish (Cho, 2006). Diets known to have positive effects on cognitive decline or prevention of dementia are based mainly on dietary patterns than single nutrient or foods. In particular, the Mediterranean diet recommends high intake of fruits, vegetables, fish, nuts, and legumes and low intake of saturated fats and high-fat dairy products such as red meat and butter (Mio et al. In many Western countries, previous studies have shown that the Mediterranean diet prevents dementia, and higher intake of vegetables, fruits, and fish lower risk of dementia. However, it is not desirable to apply the Mediterranean diet pattern in general since it may not be common or not accessible for Asians (Mio et al. Saturated fatty acids 732 Genetics, Neurology, Behavior, and Diet in Dementia and cholesterol increase the risk of vascular dementia by increasing the risk of cardiovascular disease and arteriosclerosis (Cho, 2006). This shows that eating less may help prevent dementia (Central Dementia Center, 2013; Luchsinger et al. As a result, it is desirable to reduce intake of saturated fat, lower risk of vascular disease, and increase consumption of monounsaturated and polyunsaturated fats and fish (Luchsinger et al. Taurine Taurine, a sulfur-containing free amino acid, is present in retina, skeletal muscle, and the heart, and especially in the brain at high concentrations (Kendler, 1989). Taurine is not only harmless to the human body but also plays a diverse and important physiological role in promoting growth and development of skeletal muscle cells, maintaining the immune system, development of the retina and nervous system, antioxidant activity, fatigue recovery, and blood pressure stabilization (Grimble, 2006). It plays an important role in brain function and is known to be effective in neuroprotection and cognitive improvement in various types of dementia (Barthel et al. When hypoxic or oxidative stress is applied to nerve tissue, taurine inhibits the toxic effects of excitatory neurotransmitters (Grimble, 2006). Taurine is known to be safe, and one of the characteristics that differentiates it from other amino acids is that reduction of absorption rate, growth inhibition, and other side effects were not reported even if it is consumed in excess. Also, it easily penetrates the bloodebrain barrier, and it is effective even when consumed in foods (Yoon, Choi & Shin, 2015). Taurine content among seafood was mostly high in mollusks such as webfoot octopus, beka squid, and long-arm octopus (around 1300, 700, and 600 mg taurine per 100 g, respectively) and shellfish such as ark shell, little neck clam, and hard-shelled mussel (around 1100, 900, and 800 mg taurine per 100 g, respectively). It had a high content in pacific herring and Pacific Ocean perch among fishes (around 400 mg taurine per 100 g, respectively). However, they may differ depending on the habitat and the timing of the catch (Kim, Kim & Moon, 1999). Also, taurine is weakened with high heat and may lose its content during the cooking and drying process. Thus, it is desirable to minimize the taurine loss in the processing of seafood with a high amount of taurine on the skin such as squid (Cho et al. In addition, taurine is contained in health supplements such as energy drinks and tablets, so it is easy to consume. Taurine was orally administered and was shown to activate glial cells in the brain, restoring memory and learning ability to normal levels (Kim et al. This result could be attributed to the activation of glial cells, which are associated with memory, and supports the specific association between taurine and dementia (Luchsinger et al. Also, positive association was shown between taurine index and total score of cognitive function. As a result, past taurine intake was shown to have a positive effect on the present cognitive function of the elderly, which implies taurine-rich foods may be recommended to be consumed to prevent dementia (Bae, Gao, Kim & Chang, 2017). Previous study has investigated the effects of dietary taurine supplementation on cognitive function of the elderly with dementia by providing 3 g of taurine once a day for 4 weeks. Taurine index means past taurine intake by scoring the intake frequency of taurine-containing foods. These studies showed that dietary taurine supplementation has a positive effect on the cognitive function of the elderly with dementia and may be a good nutrient for the prevention and treatment of dementia. The concentration of taurine in the body is determined by the balance between its intake, biosynthesis, and excretion. If the taurine level is insufficient, its reabsorption in the kidneys is increased and excretion reduced. On the other hand, if taurine is too abundant, it is excreted into the urine or bile (Hayes, 1985). According to one study, taurine excretion was reported to have a significant relationship with dementia. Although the taurine contents of dietary intake are almost same, comparison of the amount of taurine excretion between the elderly with dementia and normal elderly receiving the same meals found that taurine was excreted more in the urine of the elderly with dementia (Gao, Bae, Chang & Kim, 2017). Based on this result, the higher urinary excretion of taurine can be an impending sign of dementia, and studies on taurine excretion in the elderly with dementia is considered to be more necessary in the future. The evaluation method in this study might be useful for the diagnosis or prevention of dementia, and it could potentially be a biomarker for dementia. Conclusion Nutritiondto be exact, a nutritious dietdis important in the etiology and prevention of cognitive decline and functional damage. Proper nutritional intake directly promotes brain function and neurological health and can prevent or delay neurodegenerative diseases such as dementia (Stewart et al. As the prevalence of dementia is low in the elderly who have adhered to dietary guidelines for preventing dementia, proper nutritional intake should be the basis for improving quality of their life (Cho, 2006; Kang et al. Nutritional management of dementia is difficult to study due to various issues related to the disease, and there are many parts to be studied. Based on the topics dealt with in this chapter, dietary guidelines for dementia patients are suggested. There is no complete method to treat dementia yet, but adequate nutrition and eating habits improve physical status in all kinds of dementia (Cho, 2006). In the future, more sophisticated nutritional support strategies should be developed to relieve the suffering of dementia patients and their families (Han, 2000). It is desirable to reduce intake of saturated fat, and increase consumption of monounsaturated and polyunsaturated fats and fish. Dietary taurine supplementation has a positive effect on the cognitive function of the elderly with dementia and may be a good nutrient for the prevention and treatment of dementia. Taurine plays various and important roles in the human body, such as maintaining the immune system, developing the retina and nervous system, and activating antioxidants. Taurine was found to be a safe nutrient after testing in laboratory animals and humans for safety. Effects of dietary taurine supplementation on cognitive function in the elderly women with dementia. Past taurine intake has a positive effect on present cognitive function in the elderly. Readiness potential in different states of physical activation and after ingestion of taurine and/or caffeine containing drinks. Reduced lean mass in early Alzheimer disease and its association with brain atrophy. Change of taurine content in squid meat during squid processing and taurine content in the squid processing waste water. Proceedings of the National Academy of Sciences of the United States of America, 86(16), 6377e6381. Significant difference in urinary excretion of taurine between the elderly with dementia and the normal elderly. Destruction of tocopherols, carotenoids and retinol in human plasma by cigarette smoke. Factors associated with nutritional status in a group of people in an early stage of dementia. Anemia is associated with incidence of dementia: A national health screening study in Korea involving 37,900 persons. Fatty acid intake and the risk of dementia and cognitive decline: A review of clinical and epidemiological studies.

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Adenosine receptors and neurological disease: Neuroprotection and neurodegeneration women's health clinic greeley co trusted 25 mg kyliformon. Blood purine measurements as a rapid real-time indicator of reversible brain ischaemia. Reduced density of adenosine A1 receptors and preserved coupling of adenosine A1 receptors to G proteins in Alzheimer hippocampus: A quiantitative autoradiographic study. It is characterized by the progressive loss of cognitive abilities as well as by the presence of amyloid deposits and neurofibrillary tangles. Oxidative stress Imbalance between the production of reactive oxygen species and the capability of the organism to readily detoxify the reactive intermediates is called oxidative stress. Ab starts to accumulate in the brain at 6e7 months of age, and plaques appear between 9 and 12 months. Over 35 million people are affected by dementia, an emerging worldwide problem that represents high economic costs for our society (Heppner, Ransohoff, & Becher, 2015; Hurd, Martorell, Delavande, Mullen, & Langa, 2013). Clinically, it is defined by a progressive loss of cognitive functions, memory, and language. These conditions place a devastating burden on both patients and their families (Hurd et al. Human dementias may be irreversible and reversible, with many different putative etiologies. As a result of these mutations, Ab40e42 is overproduced and accumulates in the brain of these patients. Ab42 oligomerizes and deposits into extracellular plaques, promoting neuronal loss, vascular damage, and dementia (Hardy & Higgins, 1992; Heppner et al. Ab starts to accumulate in the brain at 6e7 months of age, and plaques appear between 9 and 12 months (Karen Hsiao et al. This model presents cognitive impairments, such as impaired learning and spatial memory in the Morris water maze (Karen Hsiao et al. Oxidative stress and Ab are closely related to each other, since Ab induces oxidative stress in vitro and in vivo and at the same time oxidative stress increases the production, oligomerization, and deposition of Ab (Dong et al. This is notoriously in contrast with the general view of these proteins as protective factors. This is the type of plaque seen throughout the cortex and the hippocampus, regardless of the genetic background. It may be important to identify different plaque types, as they may represent different stages of the pathology and might have different effects on the neuropathological events of the disease, including inflammation, metal contents, and neuronal loss. Therefore, in this type of study it is of the utmost importance to differentiate between the two sexes and, if possible, to study the different regions of the brain independently. The amyloid cascade was analyzed by western blot at early (w5 months) and advanced (w14 months) ages. Perhaps this apparent decreased amyloid cascade is linked to the increased formation of plaques, which could represent a protective mechanism against oligomeric Ab species, which have been described to play a central role in neurotoxicity and correlate better than amyloid plaque burden with disease severity (Braak et al. Microglia and astrocytes are closely associated with amyloid plaque deposits and are thought to contribute to their formation and/or clearance. They seem to be tissue-protective proteins by means of their potent antioxidant and antiinflammatory effects. Genetic modification of the phenotypes produced by amyloid precursor protein overexpression in transgenic mice. Relative cadmium-binding capacity of metallothionein and other cytosolic fractions in various tissues of the rat. New insight into the molecular pathways of metallothionein-mediated neuroprotection and regeneration. The native copper- and zinc- binding protein metallothionein blocks copper-mediated Ab aggregation and toxicity in rat cortical neurons. Metal binding and oxidation of amyloid-b within isolated senile plaque cores: Raman microscopic evidence. Proceedings of the National Academy of Sciences of the United States of America, 86(18), 7260e7264. The role of methallothioneins in experimental autoimmune a encephalomyelitis and multiple sclerosis. Subcellular and metabolic examination of amyloid-b peptides in Alzheimer disease pathogenesis: Evidence for Ab25e35. Proceedings of the National Academy of Sciences of the United States of America, 91(2), 584e588. Metal swap between e Zn7-metallothionein-3 and amyloid-b-Cu protects against amyloid-b toxicity. Premature death in transgenic mice that overexpress a mutant amyloid precursor protein is preceded by severe neurodegeneration and apoptosis. Metallothionein-I a overexpression decreases brain pathology in transgenic mice with astrocyte-targeted expression of interleukin-6. Proceedings of the National Academy of Sciences of the United States of America, 89(14), 6333e6337. Distal regulatory elements from the mouse metallothionein locus stimulate gene expression in transgenic mice. Endocytosis the term endocytosis is a general term describing the process of engulfing substances and particles from the extracellular space by the cell. Microtubule-associated protein tau the tau protein promotes microtubule assembly and stability. It is a multistep process in which cells engulf other cells or large solid particles. It plays an important role in multiple physiological processes, including synaptogenesis and synaptic plasticity. For instance, they point toward a transient Ab effect on miR-106b expression (Wang et al. Similarly, overexpression of miR-26b in rat primary postmitotic neurons induces tau hyperphosphorylation. This enhanced phosphorylation is caused by the miR-26b-dependent decrease in retinoblastoma-associated protein (Rb1) levels and consequent activation of cyclin-dependent kinase 5 (Cdk5) (Absalon, Kochanek, Raghavan, & Krichevsky, 2013). Overexpression of miR-195 in two-vessel-occlusion rats prevents tau hyperphosphorylation via downregulation of Cdk5r1 expression and decrease in Cdk5/p35 activity (Sun et al. Consistent with the observation of the detrimental effects of a reduction in miR-132 levels, injection with miR-132 mimic improves long-term memory in a mouse model (Salta et al. Its overexpression inhibits tau phosphorylation at tyrosine 18 by direct downregulation of Fyn kinase (Liu, Zhao, & Lu, 2016). The first one, miR-125b, modulates spine morphogenesis, and its overexpression in neurons results in the formation of longer and thinner dendritic spines (Edbauer et al. In addition, miR-125b regulates synapsin-2 (Syn2) and 15-lipoxygenase (Lox15) levels. Its expression appears to increase upon extinction training and its lentiviral-mediated knockdown impairs memory for fear extinction. This action might be exerted via 138 Genetics, Neurology, Behavior, and Diet in Dementia Table 9. Moreover, decreased levels of miR-124 in sensory neurons lead to enhancement of long-term facilitation, at least partially due to the regulation of Creb1 expression (Rajasethupathy et al. In addition to the regulation of synaptic functions, miR-34a has also been implicated in the modulation of phagocytosis. This hypothesis is supported by bioinformatics predictions and experimental evidence. Proceedings of the National Academy of Sciences of the United States of America, 104(31), 12849e12854. Proceedings of the National Academy of Sciences of the United States of America, 105(17), 6415e6420. Often, particularly vulnerable neuronal types are affected in each pathology as described in the paragraphs that follow.

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Estrogen receptor alpha polymorphisms and the risk of cognitive decline: A 2-year follow-up study birth control pills and women's health order 25 mg kyliformon visa. Neuroactive steroids: An update of their roles in central and peripheral nervous system. Immunolocalization of estrogen receptor beta in the mouse brain: Comparison with estrogen receptor alpha. Variations in memory function and sex steroid hormones across the menstrual cycle. Increased risk of cognitive impairment or dementia in women who underwent oophorectomy before menopause. Prospective analysis of the association between estrogen receptor gene variants and the risk of cognitive decline in elderly women. Plasma estrogen levels, estrogen receptor gene variation, and ischemic arterial disease in postmenopausal women: the three-city prospective cohort study. Estrogen receptor alpha gene polymorphisms are associated with estradiol levels in postmenopausal women. Hormone therapy and Alzheimer disease dementia: New findings from the Cache county study. Estrogen and/or androgen replacement therapy and cognitive functioning in surgically menopausal women. The regional brain distribution of the neurosteroids pregnenolone and pregnenolone sulfate following intravenous infusion. Estrogen receptor 1 polymorphisms and risk of cognitive impairment in older women. Effects of raloxifene on cognition, mental health, sleep and sexual function in menopausal women: A systematic review of randomized controlled trials. Proceedings of the National Academy of Sciences of the United States of America, 102(52), 19198e19203. Clathrin-mediated endocytosis functions include the internalization of receptors, recycling of membrane components, reformation of synaptic vesicles, and uptake of low-density lipoproteins and iron-saturated transferrin. Electroencephalography Is a measurement of brain electrical activity, which reflects the integrated excitatory and inhibitory postsynaptic potentials of large neuron populations. The method can be used for detection of functional cerebral abnormalities such as epileptiform activity or encephalopathy. Single-nucleotide polymorphism Is a precise position along a chromosome where the deoxyribonucleic acid of different people may vary. Generally, two alternate alleles are found at a particular singlenucleotide polymorphism. P300 is elicited using oddball paradigm, in which the subject must identify rarely occurring target items interspersed among more frequently occurring nontarget items. The information-processing cascade associated with attention, decision-making, and memory mechanisms is reflected in the P300 signal. Unraveling the biological pathways through which genes identified in association studies influence pathogenesis of neurodegenerative diseases could potentially contribute to an earlier diagnosis and the development of personalized prevention strategies (Illarioshkin et al. Impaired autophagy could result in neurotoxicity and, consequently, might also be related to the spreading of tau pathology. Changes in the amplitude of activity within specific frequency bands are robustly found to be associated with variations in overall arousal level as well as with different cognitive processes. Beta oscillations are involved in regulating cognitive and motor functions (Cannon et al. These alterations were mediated by the influence of Ab pathology on thalamocortical circuitry. Recently, in a study on transgenic mice harboring Ab and tau, it was demonstrated that these proteins have opposing effects on the activity of neuronal circuits. Ab alone causes hyperactivity, whereas tau alone suppresses activity and promotes silencing of many neurons (Busche et al. In the ApoE 4 allele carriers, neurophysiological signs of hyperexcitability were characterized by the manifestation of synchronous high-voltage delta and theta and sharp waves under hyperventilation (Ponomareva et al. Abnormal network hyperactivity contributes to cognitive decline through changes in the expression of genes and the remodeling of neuronal circuits (Palop & Mucke, 2009). Optogenetic studies directly demonstrated that chronic activation of the hippocampal perforant pathway increases Ab pathology in the dentate gyrus and hippocampus (Yamamoto et al. It is also called P300, as it occurs with a latency between stimulus and 50 Genetics, Neurology, Behavior, and Diet in Dementia response of approximately 300 ms in healthy adults. The presence, magnitude, topography, and timing of the P300 reflect the speed and efficiency of cognitive processes. These factors can negatively affect the neurophysiology of an ageing brain and cause cognitive dysfunction. Cortical sources of resting state electroencephalographic alpha rhythms deteriorate across time in subjects with amnesic mild cognitive impairment. Tau impairs neural circuits, dominating amyloid-b effects, in Alzheimer models in vivo. Using event-related potential P300 as an electrophysiological marker for differential diagnosis and to predict the progression of mild cognitive impairment: A meta-analysis. Prediction of longitudinal cognitive decline in normal elderly with subjective complaints using electrophysiological imaging. Proceedings of the National Academy of Sciences of the United States of America, 109, E2895eE2903. Chronic optogenetic activation augments ab pathology in a mouse model of Alzheimer disease. Auguste Deter was admitted to the hospital in Frankfurt am Main with signs of dementia. In 1903, Alzheimer left Frankfurt and moved to the Royal Psychiatric Clinic, Munich, which was headed by Emil Kraepelin. His report noted distinctive plaques and neurofibrillary tangles in the brain histology. In 1910, Kraepelin published the eighth edition of his textbook, Psychiatrie, where he included a report on Mrs. In 1912, Alzheimer became Director of the Psychiatric and Neurological Clinic of the Silesian University of Friedrich Wilhelm in Breslau. Any one of these nucleotides can be exchanged for another, thus altering the genetic information. Microglia Microglia are a subtype of the glial cells of the central nervous system. Microglia are essential for brain function, having multiple roles in both health and disease. Microglia act primarily as phagocytes (scavenging of cellular debris) but they are also involved in synaptic modeling, production, and secretion of trophic factors and signaling molecules. Activation of microglia can trigger inflammatory cascades potentially leading to cell and tissue damage and adversely affecting learning, memory, and other cognitive functions in the process. Pyroptosis is dependent on specific pyroptopic caspases (human caspase-1, caspase-4, caspase-5) to induce cell death. Activation of pyroptopic caspases results in rupture of plasma membrane, and the released cellular cytosol leads to an inflammatory process. Introduction Scavenger receptors are primary pathogen receptors involved in the defense reactions against a variety of pathogens. Scavenger receptors are defined as a family of molecules that share the ability to bind polyanionic ligands. They are structurally unrelated membrane receptors present on the surface of phagocytic cells such as microglia, macrophages, and dendritic cells. Currently, six classes of scavenger receptors are known; however, some scavenger receptors are yet to be categorized (Wilkinson & El Khoury, 2012). Additionally, scavenger receptors play important roles in the development of atherosclerosis and in the mechanisms of tumor growth and metastasis; yet their role in the pathogenesis of neurodegenerative disorders remains virtually unknown. The 155e183 amino acid region is binding oxidized phospholipids, oxidized low-density lipoproteins, etc. Alzheimer analyzed brain of his patient Auguste Deter post mortem and noted "miliary foci" in the cortex that are now recognized as senile plaques (amyloid beta or abeta). The question remains, however, as to the fate of the abeta proteins that are phagocytosed by microglia. Microglia express abeta-degrading enzymes including insulin-degrading enzyme, neprilysin, and matrix metalloproteinase 9, yet inhibitors of these enzymes failed to have any effect on abeta degradation. Elevated cholesterol levels in the brain have also been shown to increase the level of abeta in brain tissue (Chen, Hui, & Geiger, 2014).

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Proceedings of the National Academy of Sciences of the United States of America women's health center reno cheap kyliformon online mastercard, 90(2), 567e571. Relative frequencies of Alzheimer disease, Lewy body, vascular and frontotemporal dementia, and hippocampal sclerosis in the State of Florida Brain Bank. Accelerated amyloid deposition in the brains of transgenic mice coexpressing mutant presenilin 1 and amyloid precursor proteins. Impaired synaptic plasticity and learning in aged amyloid precursor protein transgenic mice. Bioenergetic analysis of isolated cerebrocortical nerve terminals on a microgram scale: Spare respiratory capacity and stochastic mitochondrial failure. Proceedings of the National Academy of Sciences of the United States of America, 107(43), 18670e18675. Quantitative measurement of mitochondrial membrane potential in cultured cells: Calcium-induced de- and hyperpolarization of neuronal mitochondria. Cause and consequence: Mitochondrial dysfunction initiates and propagates neuronal dysfunction, neuronal death and behavioral abnormalities in age-associated neurodegenerative diseases. Proteomic and functional alterations in brain mitochondria from Tg2576 mice occur before amyloid plaque deposition. The isolation of nerve endings from brain: An electronmicroscopic study of cell fragments derived by homogenization and centrifugation. Beneficial effects of dietary restriction on cerebral cortical synaptic terminals: Preservation of glucose and glutamate transport and mitochondrial function after exposure to amyloid beta-peptide, iron, and 3-nitropropionic acid. Proceedings of the National Academy of Sciences of the United States of America, 105(35), 13145e13150. Mitochondrial dysfunction, oxidative stress, regulation of exocytosis and their relevance to neurodegenerative diseases. Creatine kinase B deficient neurons exhibit an increased fraction of motile mitochondria. Photolysis of a caged peptide reveals rapid action of N-ethylmaleimide sensitive factor before neurotransmitter release. Proceedings of the National Academy of Sciences of the United States of America, 105(1), 347e352. Mitochondrial trafficking and the provision of energy and calcium buffering at excitatory synapses. Miro1 is a calcium sensor for glutamate receptor-dependent localization of mitochondria at synapses. Effect of amyloid beta-peptide on permeability transition pore: A comparative study. High-level neuronal expression of abeta 1-42 in wild-type human amyloid protein precursor transgenic mice: Synaptotoxicity without plaque formation. Synaptic mitochondrial changes in the motor cortex following unilateral cortical lesions and motor skills training in adult male rats. Decreased pyruvate dehydrogenase complex activity in Huntington and Alzheimer brain. Synaptic mitochondria are critical for mobilization of reserve pool vesicles at Drosophila neuromuscular junctions. Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo. The primary aim of this chapter is to outline some of these limitations in the different contexts in which this imaging modality has been found to be valuable. The specificities, or reliability that a normal scan excludes the presence of elevated amyloid pathology, range between 88% and 100%, and sensitivities, or ability for amyloid imaging to detect elevated amyloid pathology, range between 88% and 98% (Clark et al. When two or more cortical areas demonstrate this loss of contrast, the scan may be interpreted as positive for elevated amyloid. The approved assessment is visual, and the reported result is binary; the scan is either positive or negative for elevated amyloid pathology. Quantitative assessments of amyloid deposition are utilized in imaging research studies; several different methods are available, but none are approved for clinical use. Nonetheless, evidence from these studies can be applied to more adequately interpret the clinical significance of amyloid imaging results. Only nonspecific white matter binding is present with fingerlike projections of subcortical white matter (*) but no appreciable uptake in gray matter (arrows), with intact grayewhite matter differentiation indicating no to sparse b-amyloid plaque deposition. When extensive white matter pathology is present, the normal nonspecific radiotracer binding in subcortical white matter may be diminished, with regional signal reductions (Schmidt et al. Preliminary results indicate that management decisions change in about two-thirds of cases (Rogers, 2017). Changes in patient management were greater in the information group, but no significant difference was observed in cognitive change from baseline or health outcomes at 1 year when patient groups were compared (Pontecorvo et al. A limitation of utilization may include the relatively high cost of amyloid imaging (Insel et al. Radiologic diagnosis for mild cognitive impairment or early dementia the required binary visual assessment may pose a challenge for the radiologist when confronted with equivocal or indeterminate scan images (Weidman et al. Lack of a clear distinction between normal and positive findings may also be due to technical factors, such as timing of scan acquisition, inadequate resolution, head angle, motion artifact, and scanner function (Trembath, Newell, & Devous, 2015). The proficiency of the radiologist can influence accuracy of the result (Weidman et al. Even for a trained and experienced nuclear medicine physician, there will occasionally be a false-positive or false-negative result. Furthermore, in studies comparing the visual "read" with a quantitation of cortical amyloid deposition, multiple well-trained and experienced readers had to reach a consensus for a scan to be classified as positive or negative. The "real world" practice of the clinician ordering amyloid imaging is naturally differentda single radiologist will be reading the scan. In some memory centers, dementia specialists may review the scan images themselves but may not have access to a quantitative assessment for comparison when scans appear to be of lower quality, or a potentially misleading radiologic diagnosis is suspected, in equivocal or intermediate cases (Morris et al. While the visual assessment and quantification of amyloid have been shown to have a similar accuracy (Schreiber, Landau, Fero, Schreiber, & Jagust, 2015), they could be complementary to each otherdi. Even for the proficient radiologist, availability of a quantitative measurement in visually equivocal cases would likely be more adequate than relying solely on the binary read (Bullich et al. Even if a quantitation method is approved for an amyloid-beta radiotracer, the additional knowledge, equipment, and software required to determine a quantitative measurement may be too onerous to implement and utilize efficiently in daily radiologic practice. Presently, amyloid imaging for individuals without objective cognitive impairment is investigational and used in prevention trials but presently does not have a clinical purpose (Johnson, 2013). Amyloid positivity could be associated with more imminent disease risk than a positive genetic test result. First implemented in trials to verify target engagement of antiamyloid monoclonal antibodies, amyloid imaging results demonstrated that in a fair number of participants, significant amyloid burden was absent, confirming the inadequate accuracy of using only clinical criteria (Liu et al. A composite assessment at study baseline has included other factors combined with amyloid imaging or cerebrospinal fluid analysis, such as apolipoprotein-E genetic status, participant age, and baseline cognitive/function 500 Genetics, Neurology, Behavior, and Diet in Dementia composite scores. Tau burden, propagation, and topography correlate more closely with disease stage and clinical symptoms (Brier et al. The significance of amyloid positivity and negativity at an individual level will vary, and what he or she experiences after disclosure may be a dynamic process, as comprehension of scan results changes over time. Amyloid imaging is useful in assessing how effectively various concentrations of infusions of antibodies selectively targeting aggregated species of amyloid-beta reduce cortical amyloid burden (target engagement). A doseeresponse relationship for some these study drugs has been demonstrated (Sevigny, Chiao, et al. Subjective cognitive concerns, amyloid-beta, and neurodegeneration in clinically normal elderly. Resistance vs resilience to Alzheimer disease: Clarifying terminology for preclinical studies. Accuracy of the clinical diagnosis of Alzheimer disease at National Institute on aging Alzheimer disease centers, 2005e2010. Phase 3 trial of flutemetamol labeled with radioactive fluorine 18 imaging and neuritic plaque density. Communicating mild cognitive impairment diagnoses with and without amyloid imaging. Potential impact of amyloid imaging on diagnosis and intended management in patients with progressive cognitive decline. Prevalence of cerebral amyloid pathology in persons without dementia: A meta-analysis. Predictive accuracy of amyloid imaging for progression from mild cognitive impairment to Alzheimer disease with different lengths of follow-up: A meta-analysis.

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Comparison of visual and quantitative florbetapir F 18 positron emission tomography analysis in predicting mild cognitive impairment outcomes menstruation heart palpitations cheap 25 mg kyliformon with mastercard. Soluble oligomers of the amyloid beta-protein impair synaptic plasticity and behavior. Evaluation of amyloid protective factors and Alzheimer disease neurodegeneration protective factors in elderly individuals. Clinical use of amyloid-positron emission tomography neuroimaging: Practical and bioethical considerations. One of the important conclusions from these data is an outpacing decrease in neuronal number in the hippocampus as compared to hippocampal volume, suggesting decreased neuronal density in the remaining tissue. Images in the right column represent enlarged data of hippocampal areas from the middle column. Left column: correlation between cognitive tests performance and hippocampal R2t*; Right column: correlation between cognitive tests and hippocampal volume. Pearson correlation coefficients (r) and P values are shown in the left upper corners. This result is in agreement with the known dissociation between PiB-defined amyloid plaques and cognitive performancedat least 30% of people with significant amyloid burdens in their brains are cognitively normal (Morris et al. This comparison further confirms the important role of R2t* as a surrogate marker of tissue neuronal integrity. The data show that the progressive hippocampal volume atrophy is a characteristic process of a normal ageing (Price et al. This is especially important since amyloid accumulation in the brain represents the earliest changes in the course of Alzheimer disease. The data demonstrate significant correlations not only in the areas of high amyloid accumulation. This effect can be described in the framework of the theoretical model of Yablonskiy & Haacke (1994) that was previously validated on phantoms (Yablonskiy, 1998) and in vivo (He, Zhu, & Yablonskiy, 2008). Pearson correlation coefficients r and P values (corrected for multiple comparison using false discovery rate over all cortical regions) are shown in the left upper corners. The bar graph on the right shows group comparison based on the R2* measurements in the parahippocampus. Left panel shows significant R2* (surrogate marker of amyloid) differences between normal and preclinical group. Most drug trials to date fail to provide meaningful impact on disease progression, most likely because they start too late in disease progression when brain damage is already extensive. Proceedings of the National Academy of Sciences of the United States of America, 96(24), 14079e14084. Proceedings of the National Academy of Sciences of the United States of America, 110(47), E4502eE4509. Gradient echo magnetic resonance imaging correlates with clinical measures and allows visualization of veins within multiple sclerosis lesions. Pittsburgh compound B imaging and prediction of progression from cognitive normality to symptomatic Alzheimer disease. Proceedings of the National Academy of Sciences of the United States of America, 87(24), 9868e9872. Aging, sexual dimorphism, and hemispheric asymmetry of the cerebral cortex: Replicability of regional differences in volume. In vivo quantitative evaluation of brain tissue damage in multiple sclerosis using gradient echo plural contrast imaging technique. Spatial correlation between brain aerobic glycolysis and amyloid-beta (Abeta) deposition. Proceedings of the National Academy of Sciences of the United States of America, 107(41), 17763e17767. Quantitation of intrinsic magnetic susceptibility-related effects in a tissue matrix. In vivo detection of microstructural correlates of brain pathology in preclinical and early Alzheimer disease with magnetic resonance imaging. On the relationship between cellular and hemodynamic properties of the human brain cortex throughout adult lifespan. Hemolysis, elevated liver enzymes, and low platelets A severe form of preeclampsia occurring in less than 1% of all pregnancies. Placental disease All complications during pregnancy with impaired placental function. Posterior reversible encephalopathy syndrome Reversible neuroimaging findings and subcortical edema without infarction in the white matter of the brain diagnosed in patients with eclampsia, renal insufficiency, immunosuppression, or hypertension. Thus the symptoms, treatments, and prognoses differ, and when discussing long-term effects it must be kept in mind that it is possible that we are dealing with several different diseases (Vatten & Skjaerven 2004). Condition Definition Course Chronic hypertension Gestational hypertension Superimposed preeclampsia Mild preeclampsia Severe preeclampsia Hypertension diagnosed before pregnancy or before 20 gestational weeks Hypertension diagnosed after 20 gestational weeks Addition of significant proteinuria in women with chronic hypertension Blood pressure 140/90 or above. Significant proteinuria Blood pressure 160/110 plus significant proteinuria or renal, liver, cerebral, or coagulation disturbances Risk for intrauterine growth restriction and risk for superimposed preeclampsia If significant proteinuria occurs, the diagnosis is preeclampsia See below Usually mild. Progression to severe preeclampsia might follow Risk for fetal growth restriction, cerebral edema, stroke, and convulsions as well as liver and coagulation disturbances Hypertension is defined as blood pressure 140/90 mm Hg on two occasions at least 4 h apart. Preeclampsia is sometimes divided into early-onset or late-onset if diagnosed before or after gestational week 34, representing severe and mild preeclampsia, respectively. Lately it has been proposed that proteinuria should not always be mandatory for a diagnosis of preeclampsia (Brown et al. Factors linked to vascular dysfunction include chronic hypertension, pregestational diabetes, obesity, and preexisting renal disease. Genetic factors include being African American or having a family history of preeclampsia. In a normal pregnancy, cytotrophoblasts invade the spiral arteries of the uterus, and the muscular vessels are widened to allow for the increase in blood volume during pregnancy. Stage 1 represents impaired trophoblast invasion causing placental hypoxia and the release of antiangiogenic factors. Stage 2 represents the ensuing vascular dysfunction causing clinical manifestations of the disease (Roberts & Hubel, 2009). During normal pregnancy, trophoblasts change phenotype and invade the spiral arteries, thus creating low-resistance vessels that enable adequate perfusion of the placenta. In pregnancies with impaired placental function, this does not occur and the spiral arteries continue to be high-resistance vessels. The first stage consists of impaired trophoblast invasion leading to an underperfused placenta, oxidative stress, and endothelial dysfunction. The second stage is the maternal syndrome consisting of hypertension, proteinuria, liver dysfunction, coagulation disturbances, and occasionally seizures and death. Although symptoms of disease often disappear postpartum, they tend to return with age. Pregnancy complications and maternal cardiovascular risk: Opportunities for intervention and screening Neuroimaging showed reversible subcortical edema without infarction in the white matter of the brain in patients with renal insufficiency, immunosuppression, hypertension, or eclampsia. Findings were accompanied by seizures, headaches, confusion, and visual abnormalities (Hinchey et al. Three possible mechanisms have been described leading to extravasation of fluid and edema: (1) rising blood pressure along with breakdown of cerebral autoregulation, (2) endothelial dysfunction affecting the bloodebrain barrier, and (3) focal vasospasm. The neuroimaging findings are identical regardless of the underlying condition (Roth & Ferbert 2009). Differential diagnoses include severe cerebrovascular disorders such as stroke or thrombosis. Swift control of blood pressure and seizures so that secondary infarct or hemorrhage is avoided is mandatory (Cozzolini et al. Stroke and preeclampsia/eclampsia the risk of thrombosis is increased in all pregnant women due to increased coagulability. Cognitive functioning and previous preeclampsia/eclampsia Normal pregnancy does not seem to affect subjective cognitive functioning as measured with validated questionnaires. Self-reported cognitive function has been shown to be affected in previously eclamptic and preeclamptic women several years after the index pregnancy (Aukes, Wessel, Dubois, Aarnoudse, & Zeeman, 2007; Postma, Bouma et al. They also noted that few of the included studies were of high quality (Elharram, Dayan, Kaur, Landry, & Pilote, 2018).

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Proceedings of the National Academy of Sciences of the United States of America womens health today discount kyliformon generic, 104(47), 18760e18765. Amyloid deposition is associated with impaired default network function in older persons without dementia. Journal of Experimental Psychology: Human Perception and Performance, 22(2), 461e479. Functional neural correlates of attentional deficits in amnestic mild cognitive impairment. Neuronal responses related to the novelty and familarity of visual stimuli in the substantia innominata, diagonal band of Broca and periventricular region of the primate basal forebrain. Specifically, apathy can be "emotional-affective" when there is inability to create the necessary link between emotional-affective responses and the behavior. Cognitive apathy refers to difficulties in planning actions and using working memory abilities and set-shifting. Autoactivation apathy causes the failure to self-activate thoughts or actions with respect to a relatively spared ability to generate behavior. Environmental dependency phenomena Patients tend to imitate the movements of the examiner even when they have not been asked to do so, and continue emulating despite being requested to stop. Executive Functions Set of processes that include: the ability to plan and evaluate effective strategies related to a specific purpose related to problem-solving skills and cognitive flexibility; attentional control, referring to the ability to inhibit interfering stimuli and to activate the relevant information; the inhibitory control and decision-making processes that support the selection of the functional response and the modification of the response (behavior) in relation to the change of the environmental contingencies. Introduction Cognitive deficits due to damage or disease affecting frontal lobe systems are well known, and they may result in a frontal syndrome attributable to dysfunction of the frontal lobe circuits (Bonelli & Cummings, 2007). Frontal lobe lesions determined by progressive degenerative or acute pathologies can disrupt multiple circuits because of their close proximity to one another. Cognitive deficits mainly encompass language impairments and executive disorders (dysexecutive syndrome), while behavioral changes primary concern social and affective processes (frontal syndrome) (Cummings & Miller, 2007). Although the terms "frontal syndrome" and "dysexecutive syndrome" are often used interchangeably, several studies have pointed out that the terms should be distinguished. Disturbances of social cognition are early and salient features of many major psychiatric diseases, brain injury, and neurodegenerative disorders. The neural correlates are linked for example to abnormalities in the orbitofrontal cortex (social inappropriateness, hypersexuality, and compulsive gambling) (Beer John, Scabini, & Knight, 2006) or in the dorsomedial prefrontal cortex (processing of social information and decision-making) (Henry, Von Hippel, Molenberghs, Lee, & Sachdev, 2016). Neuroanatomy of the main frontal lobe circuits the frontal lobes are within the brain regions anterior to the central sulcus and fill around one-third of the whole cerebral cortex. The frontal cortex can be divided into four main areas: precentral cortex, premotor cortex, prefrontal cortex, and orbitofrontal cortex. According to Alexander (1986), at the frontal lobes levels, multiple frontalesubcortical circuits can be described. This model provided comprehensive reviews of five neuroanatomical circuits connecting regions of the frontal lobes with subcortical structures, such as the striatum, globus pallidus, and thalamus and has specific target regions in the frontal lobes, including: the supplementary motor area, the frontal eye fields, the dorsolateral prefrontal cortex, the orbitofrontal cortex, and the medial frontal cortex. A schematic representation of the basic structure of frontal-subcortical circuits can be found in Cummings (1993). The prefrontal cortex, together with its underlying subcortical regions, is interconnected with the major sensory and motor systems of the brain. It contains the nucleus accumbens, the globus pallidus and substantia nigra, and the thalamic nucleus. The frontal poles have been considered to be involved in processes that define us as human, as they have a prominent role not only in consciousness, self-awareness but also in social cognition abilities. Frontal lobe syndromes Building upon the neuroanatomical work described above, Cummings (1993) proposed a model linking the three frontoestriatoethalamic circuits to the three clinically observable frontal behavioral syndromes (Table 39. Brain circuit Function Syndrome Dorsolateral Orbitofrontal Mesial frontal Cognition Emotion Motivation Disorganized Disinhibited Apathetic Frontal lobe syndrome and dementias 621 Executive functions refer to the set of mental processes necessary for the elaboration of adaptive cognitive-behavioral schemes in response to new and challenging environmental conditions (Hoffman, 2013). These mechanisms are able to optimize performance in situations that require simultaneous activation of different cognitive processes (Logie, 2016). The clinical pictures deriving from the dysfunction of the executive processes characterize the dysexecutive syndromes. Several studies in the literature agree on considering the prefrontal cortex the main neural substrate of these functions. Patients with lesions restricted to this network typically present decreased fluency, perseveration, difficulty shifting set, poor recall/retrieval of information, reduced mental control, limited abstraction ability, and poor response inhibition but intact perception, calculation, language ability, and storage of memories. Traditionally, the ventral orbitofrontal region plays an important role in the social behavior. The results of these studies show that the orbitofrontal regions are particularly involved in decision-making processes and in the ability to modify behavior based on changes in environmental contingencies. Lesions in these areas, in fact, produce difficulty in metacognitive, sociocognitive, emotional, and reward processing. Moreover, recent studies indicate that this brain region is particularly involved in the ability to decide when the external situation has characteristics of low structuring, i. Lesions specific to this network may produce apathy, lack of motivation, decreased interest, engagement with the environment, and poor behavioral maintenance. Frontal lobe syndrome and dementias 623 Neuropsychological assessment Several neuropsychological tests have been developed to assess frontal lobe functions. Among many of the batteries used to evaluate executive functions, a selection of specific tests can be adopted. The most useful tasks to assess executive functions could be the fluency tasks that have been often proposed as they examine the ability to maximise the number of responses under constraint of time and restricted search conditions (words or figures) while avoiding response repetition. Moreover, inhibitory functioning can be assessed by the Stroop Test or the Hayling Test of sentence completion; abstraction and reasoning using a subtest of the Behavioral Assessment of the Dysexecutive Syndrome, the Progressive Colored Matrices, the Wisconsin Card Sorting Test, and the Brixton Test. The behavior alterations can be measured using informant-based questionnaires like the Frontal Behavioral Inventory. Since social cognition and emotion recognition can be also impaired due to a frontal lobe dysfunction, tests like the Reading the Mind in the Eyes test or the Ekman faces have been used to quantify this difficulties. Frontal lobe syndrome in neurodegenerative diseases Several studies showed that the frontal lobes are particularly vulnerable to the ageing processes of the brain. Neuroimaging data on brain morphology suggest that normal ageing mainly involves cortical and subcortical structures and also the white matter fibers of the frontal lobes. Despite some methodological concerns, numerous neuropsychological studies indicate a particular susceptibility of the executive functions to the normal ageing process (Fjell, Sneve, Grydeland, Storsve, & Walhovd, 2016; Lustig and Jantz, 2015). Many neurodegenerative diseases can present an involvement of the frontal lobes, and the related functions, not only in an intermediate or advanced stage of the disease but also in a very early phase. Dementias with a prevalent involvement of the frontal lobes can cause damage of the subcortical frontal circuits involved in the regulation of cognition, emotions, and behavior. During the intermediate phase of the disease, deficits of executive functions (such as problem-solving, planning, and abstraction) are associated to the neuropsychiatric symptoms. Neuropsychiatric symptoms such as apathy, disinhibition, psychosis, vagrancy, and social withdrawal are common during this stage (Kales, Gitlin, & Lyketsos, 2014). The spectrum of the frontal variant also includes behavioral disorders characterized by disinhibition, apathy, and compulsiveness. They collected, for most of them, neuropathological data or at least biomarker examinations. The disease has an insidious onset and progresses slowly with a duration that usually goes from 10 to 14 years. They can be distinguished by the different profiles of cognitive and speech/language deficits and by a supportive pattern of atrophy on imaging (Gorno-Tempini et al. The correct classification of these variants requires the use of ad hoc speech/language and nonlanguage neuropsychological tests to define the whole profile. In particular, the damage that also involves the amygdala determines the three specific symptoms of disinhibition, stereotypies, and a grade of greed (Rolls, 2017). Patients presenting with a prevalent atrophy of the right frontal lobe show a dyscontrol of impulses, aggression, financial impudence, impulsivity, and lack of empathy; while patients with a prevalent left frontal lobe atrophy present more linguistic disorders (Mychack, Kramer, Boone, & Miller, 2001). Some patients show hyperactivity, while others may be completely apathetic and inert with a total lack of initiative and poor reaction to external stimuli. In other patients, compulsive characteristics prevail, such as stereotyped, ritualistic behaviors with respect to personal hygiene, dressing, and food. At the first neuropsychological examination, patients may initially not experience major difficulties in executive functions, as revealed by the scores obtained from specific cognitive tests. Executive deficits may appear in the course of the disease, such as planning and reasoning impairments (Hornberger, Piguet, Kipps, & Hodges, 2008). The diagnosis arises in the presence of a clear dementia syndrome, with pronounced variations in attention associated with recurrent visual hallucinations, generally well structured, and extrapyramidal motor disorders (McKeith et al. Furthermore, many patients may show a combination of cortical and subcortical neuropsychological deficits, with marked attention disorders, relevant subcortical frontal dysfunctions, and also visuospatial disorders. In particular, short-term verbal memory deficits may be present in the early phase of the disease; some studies have detected the presence of a frontal lobe and hippocampal atrophy (Aarsland, Ballard, & Halliday, 2004), so that the deficit of the executive functions could be determined by a dysfunction of the frontohippocampal projections.

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A study of premorbid personality and behavioural and psychological symptoms of dementia in nursing home residents pregnancy yeast infection treatment trusted 50 mg kyliformon. Involvement of people with dementia in raising awareness and changing attitudes in a dementia friendly community pilot project. Informant reports of changes in personality predict dementia in a population-based study of elderly African Americans and Yoruba. Quality of care in frail older people: the fragile balance between receiving and giving. From social network to safety net: Dementia-friendly communities in rural northern Ontario. Family history and its relationship with dementia stigma beliefs among Chinese Americans. Examining the differences in the stigma of dementia and diabetes among Chinese Americans. Exploring the impact of a culturally tailored short film in modifying dementia stigma among Chinese Americans: A pilot study. E-Mental health in ethnic minority: A comparison of youtube and talk-based educational workshops in dementia. Distinctive differences in the topographical distribution pattern of the neurofibrillary lesions enable the observer to assign a given autopsy case to one of six stages. Capgras delusion: Patients believe that a familiar person is someone else, has been reduplicated, or is an imposter. Cerebral amyloid angiopathy: One form of vascular pathology, defined as deposits of amyloid in the vessel walls that increase risk of hemorrhage and ischemia. De Clerambault syndrome or erotomania: the delusional belief that one is secretly loved by another. The delusion of theft: Is most closely linked to the erroneous conviction that an intruder periodically enters the home, which, in such cases, absolves caregivers from accusations of being thieves. The phantom boarder syndrome: Patients believe their house is inhabited by unwelcome guests. Delusions in dementia are associated with adverse outcomes such as aggression, caregiver stress, and earlier institutionalization (Fischer, Bozanovic-Sosic, & Norris, 2004). In some (but not all) studies of dementia, psychosis was associated with older age. Educational level Gender Deutsch, Bylsma, Rovner, Steele, & Folstein (1991) Ethnicity Vik-Mo et al. The studies of association with gender are ambiguous, but the majority are inclined toward an association with the female gender. Studies have shown impaired frontal lobe metabolism, higher density of senile plaques in the frontal cortex, and deficits in frontosubcortical circuits. Some studies showed a relationship with more rapid and severe cognitive decline, while others showed only mild differences. Delusions in dementia are associated with myocardial infarction and with acute phase of coronary disease. Delusions show heritability up to 61% and have been proposed as a marker for a disease subtype suitable for gene mapping efforts. The aim of the present chapter was to shed light on the relationship among delusions and the most frequent forms of dementia of various etiologies in terms of epidemiology, risk factors, neuroanatomy, neurochemistry, neurobiology, and relationship to cognition. Delusions have received even less attention in vascular dementia (VaD), and although the studies have limited sample size, the prevalence rates of delusion in VaD range from 15% to 36%, with persecutory delusion being the most common (25%) (Tsai, Hwang, Yang, & Liu, 1997). Delusions of persecution make up approximately 45%e60% of delusional beliefs in dementia. The strong association between delusions and hallucinations emerged in a cross-sectional case-control study where 9% of patients (30 out of 342 patients) experienced both delusions and hallucinations (Bassiony & Lyketsos, 2003). Several types of delusions for several types of dementia Delusions can be categorized within two subgroups: delusions of misidentification, associated with auditory and visual hallucinations (Cook et al. Delusions of persecution make up about 45%e60% of delusions in dementia (Webster & Grossberg, 1998). Misidentification of familiar persons (in which patients insist that familiar persons are not who they really are), the Capgras delusion, and the phantom boarder syndrome make up the majority of delusional misidentifications at 16% (Harwood et al. The rates of delusional jealousy or Othello syndrome in dementia found in the study of Tsai et al. Secondary erotomania or De Clerambault syndrome can occur in the context of organic disorders such as dementia (Cipriani, Logi, & Di Fiorino, 2012). Risk factors Known risk factors for delusions include depression and anxiety, advanced age, and limited education (Bassiony & Lyketsos, 2003), while the role of gender and ethnicity is less clear (Kotrla et al. It appears to be an association of delusions with advanced neuropathology, selective frontal lobe dysfunction, preserved intellect, and rapid cognitive decline (Fischer et al. Significant risk factors include also impaired hearing but not impaired vision (Bassiony & Lyketsos, 2003), use of antihypertensive medication, myocardial infarction, and congestive heart failure (Ostling & Skoog, 2002). Some findings suggest that disease-related factors, in interaction with medications, account for psychotic features, rather than medication alone (Fenelon, Mahieux, Huon, & Ziegler, 2000). Another hypothesis is that denervation hypersensitivity of mesolimbic and mesocortical dopaminergic receptors predisposes patients to a hypersensitivity response that manifests as psychosis (Ravina et al. Older patients suffering from hallucinations often live alone, are unmarried or without children, tend to be African American, and have a lower level of education (Cook et al. Finally, Friston (2010) proposed that beliefs (both normal and abnormal) arise through a combination of innate or endowed processes, learning, experience, and interaction with the world. Neuroanatomy and neuroimaging Neuroimaging and behavioral studies suggest a frontotemporal localization of delusions in the elderly, with right hemispheric lateralization in delusional misidentification and left lateralization in delusions of persecution (Holt & Albert, 2006). Delusion content in the group was split in simple persecutory beliefs/delusions of misidentification. It was not clear how to separate the effect of temporal lobe abnormalities from that of cortical atrophy in dementia associated with delusions (Holt & Albert, 2006). This area of hypoperfusion corresponds with location of the fusiform face area and parahippocampal place area, which show increased activation after viewing faces and physical locations, respectively. Frith and Frith (2001), for instance, proposed that prefrontal and parietotemporal parts of the neocortex are involved in mental state attribution and emotion recognition, both aspects of social cognition being critically involved in the formation of delusional beliefs. In this regard, case studies suggested that right frontoparietal infarcts may determine the onset of Capgras delusion in dementia (Forstl et al. At least 30% of Othello syndrome cases in the literature showed a neurological basis for delusion of infidelity, although its biological basis is not fully understood (Cipriani, Vedovello, Nuti, & di Fiorino, 2012). Several case reports have suggested that the right frontal lobe is the neuroanatomical correlate for delusional jealousy (Luaute, Saladini, & Luaute, 2008). It is hypothesized that focal damage to the right hemisphere and frontal lobes may play an important part in the genesis of "content-specific delusions" due to the role of the right hemisphere in producing the experience of familiarity and the role of the frontal lobes in correcting misperceptions on the basis of new information. This model highlights the dual effects of loss of function due to damage of the right hemisphere and release of inhibition due to hyperactivity of the intact left hemisphere (Devinsky, 2009). Soluble Ab induces loss of dendritic spine synapses through impairment of long-term potentiation. Nevertheless, Lewy body pathology may contribute in some cases, especially in individuals with neocortical stage Lewy body pathology (Ballard et al. Recent studies showed an association between the regulation of synaptic zinc by the zinc transporter ZnT3 and delusions (Whitfield, Francis, Ballard, & Williams, 2018). Delusions in dementia typically begin early in the course of illness, and dissipate as the disease reaches moderate to severe severity (Bassiony & Lyketsos, 2003). Delusions of misidentification appear at a somewhat later age than persecutory delusions and reflect greater cognitive decline. Persecutory symptoms showed to require a threshold level of preserved cognitive function to sustain. The rate of impairment was higher in cases with combined hallucinations and delusions than in cases with isolated delusions. Thus, vascular pathology and reduced information processing speed may be risk factors of psychosis in dementia that are modifiable by cardiovascular disease prevention (Vik-Mo et al. Epidemiological and clinical studies showed evidence for increased peripheral inflammatory markers in psychosis spectrum disorders (Radhakrishnan, Kaser, & Guloksuz, 2017), and systemic inflammation is known to contribute to cerebrovascular pathologies and cognitive impairment. The role of dopamine in signaling salience supports that aberrant dopamine signaling is the first stage of delusion formation. Neuropsychiatric symptoms in Alzheimer disease, vascular dementia, and mixed dementia.