R A Sweet

..Genetic variations in CLU, PICALM, and CR1 are associated with Alzheimer's disease, but it is unknown whether they exert their effects by altering cognitive trajectory in elderly individuals at risk for the disease...

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..These preliminary findings suggest that AD is the predominant neuropathologic condition in LLMD subjects with dementia. Further assessment of the role of comorbid cerebrovascular disease and comorbid DLB is needed...

..Future studies should examine the linkage and association of psychosis with genetic variation within these families...

..This may contribute to impairments in auditory sensory processing that are present in subjects with schizophrenia...

..Variability of regional volume estimates was readily constrained using a multifaceted approach to reduce potential sources of variability in regional delineation...

..Examination of variation at ERE6 in subjects with schizophrenia, and further examination of the independent and additive effects of variations in COMT on gene expression, is warranted...

..We recently found that AD subjects homozygous for long alleles (l) of an insertion/deletion polymorphism in the promoter region of the serotonin transporter (5-HTTPR) had elevated rates of aggressive behavior...

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..These findings need to be confirmed in additional well-powered samples...

..To conduct the first randomized study comparing the efficacy of an antidepressant alone versus an antidepressant plus a neuroleptic in the treatment of late-life psychotic depression...

..Further exploration of atypical properties of DAPZ should include de novo administration of this metabolite in animal models...

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..Lewy bodies (LB) are present in at least 20% to 30% of persons with Alzheimer disease (AD) and contribute to the risk of psychosis and to excess cognitive burden...

..To examine if selected polymorphisms in the dopamine receptor genes DRD1, DRD2, DRD3, and DRD4 are associated with the presence of psychosis or aggressive behavior in patients with Alzheimer disease (AD)...

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..These findings suggest that rigidity is associated with DAT independently of any concurrent psychotic or depressive process, whereas bradykinesia does not appear to be specific to DAT among late-life neuropsychiatric illnesses...

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..The association of AD+P with a more rapidly progressive course of AD appears to be mediated by a neuropathologic process other than increased severity of plaque and tangle formation...

..This study seeks to determine whether the degree of cognitive impairment and cognitive decline in early AD predicts subsequent AD + P onset...

..Linkage analysis of families with LOAD+P identified one significant and several suggestive novel linkage signals, which bolsters the conjecture of greater etiologic homogeneity...

..Psychotic symptoms in patients with AD (AD with psychosis [AD+P]) define a phenotype characterized by more rapid cognitive and functional decline and a liability to aggressive behaviors...

..Further exploration of the relationship between depressive symptoms and psychosis in patients with AD is warranted...

..We hypothesized that these two groups differed in their patterns of cognitive impairment, compared with AD subjects without psychosis...

..Subsyndromal psychosis might be useful for classifying AD+P families for genetic mapping studies. Prospective confirmation is required...

..We discuss possible genetic models of psychotic symptoms in AD, and suggest strategies for further investigation. Identification of such genetic factors may facilitate gene-mapping studies for both AD and idiopathic psychoses...

..There are no long-term studies of the effects of memantine in combination with ChEIs use in Alzheimer disease (AD). This study was conducted to examine the effects of ChEIs and memantine on time to death and time to NH admission...

..The findings support the hypothesis that these two genetic determinants of AD risk do not contribute to the risk of development of psychotic symptoms in AD...

..Onset of response to nortriptyline was not affected. Allelic variation of 5-HTTLPR may contribute to the variable initial response of patients treated with a selective serotonin reuptake inhibitor...

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..To determine the relationship between major depression and the presence of Lewy bodies (LBs) in patients with Alzheimer disease (AD)...

..Valid receptor-selective antipsychotic assays can be established and may have utility for dissecting the in vivo activity of atypical antipsychotics in relation to specific outcomes in clinical trials...

..g., average fluorescence intensity of proteins of interest). Importantly, the segmentation method presented can be easily adapted for use with most existing microscopy analysis packages...

..The identification of molecular alterations in these circuits is providing critical insights for the rational development of new therapeutic interventions...

..To determine the relationship between depressed mood and the development of Alzheimer disease in cognitively normal individuals...

..To examine the incidence of dementia in subjects with mild cognitive impairment (MCI) in the Cardiovascular Health Study Cognition Study...

..This did not result from an interaction of HTR2A genotype with antidepressant use. Psychosis onset in AD is strongly associated with severity of depressive symptoms, an association that may be modified by HTR2A genotype...

..CYP2D6 inhibition by paroxetine, which effectively converted 59% of patients to phenotypic PMs, may be especially relevant for elderly patients given their generally higher concentration of paroxetine...

..In AD, the prevalence of low vitamin B12 serum levels is consistent with that found in community-dwelling elderly persons in general but is associated with greater overall cognitive impairment...

..Although AD+P has been inconsistently associated with more severe neuropathology, no prior studies have examined measures of neuronal and synaptic integrity...

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..g., aggression, agitation) and sleep disorders in AD. Although the use of SHA has a proven deleterious effect on patients with AD, their use has increased over the past two decades...

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..Education and race were independently associated with psychosis. However, while education was associated with psychosis in mild/moderate stages, race was associated with psychosis in moderate/severe stages...

..We also predicted that APOE4 allele frequency would be increased among subjects with LLD...

..Our approach represents a powerful new method for stereologic estimation of features of interest within individual layers of cerebral cortex, with applications beyond the current study...

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..To describe the effect of cholinesterase inhibitors (CEIs) on the natural course of Alzheimer's disease (AD) using clinically meaningful outcomes...

..43. This is a potential candidate gene for AD as this is expressed in the brain and is involved in lipid metabolism. These findings need to be confirmed in additional samples...

..These findings support the usefulness of [18F]altanserin as a radioligand for PET studies of 5-HT2A receptors...

..We believe that current criteria for DLBs are useful when DLBs occur in isolation, but have low sensitivity when Lewy bodies coexist with the pathological abnormalities of Alzheimer disease...

..We therefore used latent class modeling to characterize trajectories of cognitive and behavioral decline in a cohort of AD subjects...

..Specific attention is given to familial aggregation and heritability, linkage to chromosomal loci, and associations of candidate genes of APOE and the monoamine neurotransmitter system...

..An individualised risk-benefit assessment is necessary for the younger patient in whom prophylactic use of anticholinergic drugs is considered...

..Consequently, in this study we sought to determine whether the lower glial cell number was due to fewer oligodendrocytes as opposed to lower numbers of astrocytes...

..This reduction may contribute to impairment in auditory function. The correlated reductions of somal volume in BA42 and BA9 suggest that a common factor may affect deep layer 3 pyramidal cells in both regions...

..This pattern of abnormalities is consistent with impairments of auditory feedforward projection neurons...

..CONCLUSION: Multiplicity of symptoms may represent a useful means for defining a genetically determined LOAD+P phenotype...

..Longitudinal study is needed to determine whether these proposed subtypes remain stable and independent over time or merge into a single group over the course of illness...

..These results were unchanged when concentrations were corrected for total daily risperidone dose. Among elderly subjects, risperidone and 9-OH clearance do not decline with increasing age or declining CrCl...

..Our results suggest that NRG1 plays a role in increasing the genetic risk to positive symptoms of psychosis in a proportion of LOAD families...

..CONCLUSION: The results of this study highlight the need for prospective assessments of depot neuroleptic dose requirements in older patients suffering from primary psychotic disorders...

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..The proposed studies may provide a basis for future interventions to improve sound processing in individuals with this illness, and to prevent loss of sound circuit components during the early stages of disease. ..

..The proposed studies may provide a basis for future interventions to improve sound processing in individuals with this illness, and to prevent loss of sound circuit components during the early stages of disease. ..

..These findings may guide the development of interventions for the prediction, treatment, and/or prevention of psychosis and excess cognitive morbidity in AD. ..

..These findings may guide the development of interventions for the prediction, treatment, and/or prevention of psychosis and excess cognitive morbidity in AD. ..

..This knowledge will guide the design of future investigations of auditory cortex pathology, and inform the interpretation of psychophysiology investigations and neural modeling of auditory processing in schizophrenia. ..

..These findings may guide the development of interventions for the prediction, treatment, and/or prevention of psychosis and excess cognitive morbidity in AD. ..