Neill R Graff-Radford

..Observations in laboratory animals suggest intraventricular pulse pressure (systolic-diastolic) may play a role in ventricular enlargement...

..Hearing loss present in 50% did not influence TICS-m or CDR performance. Using stringent entry criteria and the telephone CDR, this method accurately identified normal elderly persons...

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..To develop preventive therapy for Alzheimer disease (AD), it is essential to develop AD-related biomarkers that identify at-risk individuals in the same way that cholesterol levels identify persons at risk for heart disease...

..To test for replication of the association between variants in the CLU, CR1, and PICALM genes with Alzheimer disease...

..Single nucleotide polymorphisms that influence gene expression (eSNPs) constitute an important class of functional variants. We therefore investigated the influence of the novel LOAD risk loci on human brain gene expression...

..While variability exists, most cases with this mutation have a characteristic spectrum of demographic, clinical, neuropsychological, neuroimaging and especially neuropathological findings...

..4,617 controls) and PD (678 PDs vs. 712 controls) for association with disease risk (case-controls), age-at-diagnosis (cases) and brain gene expression levels (autopsied subjects)...

..Further studies are needed to address the molecular mechanism of clinical and pathological heterogeneity of c9FTD/ALS due to mutations in C9ORF72...

..Our findings indicate that repeat expansion in C9ORF72 is a major cause of both FTD and ALS...

..These data should enhance interpretation of individual test performances and facilitate analysis of neuropsychological profile patterns in older African American patients who present for dementia evaluations...

..Our aim was to assess the safety, tolerability, and efficacy signal of early donepezil administration with regard to enhancing recovery in a diverse acute ischemic stroke population...

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..The study investigates the effects of genetic factors on the pathology of Alzheimer's disease (AD) and Lewy body (LB) diseases, including Parkinson's disease and dementia with Lewy bodies...

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..These finding extend prior research suggesting a cognitive profile that can aid in the clinical diagnosis of DLB. Early attention and visual perceptual disturbance suggests DLB, while early impairment in memory and naming suggests AD...

..On the other hand, there is no histopathologic feature or combination of features that is pathognomonic. Neuronal intranuclear inclusions are virtually always present, but they can be detected in PGRN(-) cases...

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..We anticipate that these data will enhance the diagnostic utility and clinical interpretation of WMS-R performance in older African Americans...

..In most cases, the use of MOAANS norms should improve diagnostic accuracy in dementia evaluations of African American elders...

..The current study presents a reappraisal of the original MOANS DRS norms, provides robust and expanded norms based on a sample of 894 adults age 55 and over, and critically evaluates the benefits of robust norming...

..No meaningful association between the repeat length of the normal alleles of the GGGGCC repeat in C9ORF72 and disease phenotype or age at onset was observed in C9ORF72 mutation carriers or nonmutation carriers...

..In summary, we provide additional evidence for the variant near BIN1 (rs744373) as a LOAD risk modifier, but our results indicate that the effect of EXOC3L2 independent of APOE ε4 should be studied further...

..This provides further evidence in support of including RBD as one of the core diagnostic features of DLB...

..Overall, this large, independent follow-up study for 15 of the top LOAD candidate genes provides support for GAB2 and LOC651924 (6q24.1) as risk modifiers of LOAD and novel associations between PGBD1 and EBF3 with age-at-onset...

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..Here we examine the role of miRNAs in FTLD patients with TAR DNA-binding protein 43 pathology (FTLD-TDP) caused by genetic mutations in the progranulin (PGRN) gene...

..06) but not cerebellum. These results suggest a modest role for KIBRA as a cognition and AD risk gene, and also highlight the multifactorial complexity of its genetic associations...

..In addition, preliminary cross-validation was performed in a clinical comparison sample of another 22 older adults. The findings are discussed in the context of potential clinical and research applications...

..To validate a questionnaire focused on rapid eye movement sleep (REM) sleep behavior disorder (RBD) among participants in an aging and dementia cohort...

..This exploratory study examined whether SNCA variants may also promote successful aging as defined by survival without neurological disease...

..To investigate whether prostate cancer patients receiving leuprolide demonstrated objective cognitive decline accompanied by a change in plasma levels of amyloid-β...

..abstract:..

..These findings may help clinicians and researchers to characterize with greater precision the temporal changes in confrontation naming ability...

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..Atrophy of anterior corpus callosum may be a potential neuroimaging marker to differentiate corticobasal degeneration from progressive supranuclear palsy in patients with Richardson syndrome...

..The findings raise the possibly of an as yet identified protein that may play a pathogenic role in tau-negative FTLD...

..As such, WAIS-R normative estimates are not presented here. Interested readers who wish to obtain a full set of MOAANS WAIS-R norms, however, are invited to contact the authors for these data...

..In addition, a multicenter trial is described in which some aspects of diagnosis and longitudinal measurement in the frontotemporal lobar degenerations are being specifically explored...

..We sought to characterize the polysomnographic (PSG) findings in a series of DLB patients with sleep-related complaints...

..Our findings have implications for the design and interpretation of eGWAS in general and the use of brain expression quantitative trait loci in the study of human disease genetics...

..Hippocampal sclerosis (HpScl) in the elderly is often associated with neurodegeneration...

..Gly475del) was identified, however in vitro studies did not reveal abnormal localization of p.Gly475del mutant FUS. These findings suggest that not all exonic indels in FUS cause disease...

..The most promising rs3741916 variant is unlikely to be functional given opposing effects in different series. Identification of functional variant(s) in this region likely awaits deep sequencing...

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..We aimed to compare clinical and neuropathological features between typical and atypical AD cases...

..We examined the clinical and pathologic phenotypes of GRN mutation carriers with the pathogenic A9D (g.26C>A) missense mutation...

..Recently, we reported that mutations in the colony-stimulating factor 1 receptor (CSF1R) gene cause HDLS. In this study, we determined whether CSF1R mutations are also a cause of POLD...

..Furthermore, the apolipoprotein epsilon4 allele (APOE epsilon4) may be associated with Pick disease...

..This finding opens avenues for future research into GRN biology and the pathophysiology of neurodegenerative diseases...

..Translational regulation by miRNAs may represent a common mechanism underlying complex neurodegenerative disorders...

..The insulin-degrading enzyme gene (IDE) is a strong functional and positional candidate for late onset Alzheimer's disease (LOAD)...

..Our findings widen the phenotypic presentation for the TDP-43 p.N267S substitution and support a possible role for rare TDP-43 mutations presenting with Parkinson's disease...

..We propose that plasma GRN levels could be used as a reliable and inexpensive tool to identify all GRN mutation carriers in early-onset dementia populations and asymptomatic at-risk individuals...

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..These findings afford a finer characterization of the psychometric properties of the BNT and expand our understanding of between-group performance...

..Genome-wide association studies (GWAS) have recently identified CLU, PICALM, and CR1 as novel genes for late-onset Alzheimer disease (AD)...

..Exercise should not be overlooked as an important therapeutic strategy...

..There are several candidate outcome measures -- including the FTLD-CDR and the cognitive composites -- that could be used in clinical trials across the spectrum of FTLD...

..0 x 10(-7)) and 1.26 (95% CI = 1.05-1.51) for female heterozygotes (P = 0.01) compared to female noncarriers. For male hemizygotes (P = 0.07) compared to male noncarriers, the odds ratio was 1.18 (95% CI = 0.99-1.41)...

..Some kindreds with PGRN mutations exhibited lateralized topography of degeneration across all affected individuals...

..No patient experienced visual hallucinations. If confirmed by a prospective study, the absence of visual hallucinations may help to distinguish corticobasal syndrome from other parkinsonian syndromes...

..To determine whether apolipoprotein E (apo E) genotype influences intellectual achievement in cognitively normal individuals...

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..TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT00805792...

..These genes have high relevance to brain structure. This is the first voxelwise genome wide association study to our knowledge, and offers a novel method to discover genetic influences on brain structure...

..In contrast, FTD with Pick bodies is rare. Although there are strategies to help patients and their families, there is no known treatment for the disease...

..49, 95% confidence interval (CI) of 1.13-1.97, uncorrected P = 0.005], but not in females. In summary, these studies identify a functional apoE receptor SNP that is associated with AD in a sex-dependent fashion...

..This was found in both males and females. Results suggest that a significant proportion of patients with NPH may have congenital hydrocephalus that becomes symptomatic later in life...

..Acknowledging and focusing on the remaining positive attributes of a person with AD can be helpful to both family members and professionals...

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..DNA analysis of the proband did not detect any known mutation in tau exons 1-5, 7, or 9-13. To our knowledge, this is the first family presenting with hereditary aphasia in which typical PPA occurs in all affected members...

..01), accounting for 7.3% and 3.1% of shared variance, respectively. Significant associations were also present in NC and AD groups separately. These results indicate that it may be useful to consider Cr levels when measuring plasma Abeta...

..The epsilon4 allele may thus be associated with a specific neurocognitive phenotype among patients with AD, with the overall pattern of cognitive asymmetry dependent upon epsilon4 dose...

..Prior studies of B vitamins to reduce homocysteine in AD have not had sufficient size or duration to assess their effect on cognitive decline...

..These norms should help improve interpretation of DRS performance in African Americans and allow for greater diagnostic accuracy in patients with early cognitive decline...

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..South), parental education and literacy, and percentage of segregation in schooling. Implications of these results are discussed, as are areas for further inquiry...

..To evaluate the utility of Mini-Mental State Examination (MMSE) scores in detecting cognitive dysfunction in a sample of highly educated individuals...

..Frontotemporal lobar degeneration (FTLD) is an uncommon degenerative dementia that presents with focal cognitive and behavioral deficits...

..Primary progressive aphasia (PPA) is a language-based dementia characterized by fluent or nonfluent language disorder as its principal feature...

..The association between Alzheimer disease (AD) and genotypes at the apolipoprotein E (APOE) locus has been confirmed in numerous populations worldwide, but appears to be inconsistent in African American subjects...