Knopman, David S.

ObjectiveTo investigate the psychometric properties of the Clinical Dementia Scale—frontotemporal lobar degeneration (CDR‐FTLD) psychometric properties using Rasch analysis and its sensitivity distinguishing disease progression between FTLD and Alzheimer's disease (AD).MethodsOf 603 consecutive patients from the National Alzheimer Coordinating Center dataset (FTLD = 350; AD = 253), 120 FTLDs were included in a Rasch analysis to verify CDR‐FTLD psychometric properties; 483 (FTLD = 230; AD = 253) were included to analyse disease progression, with 195 (FTLD = 82; AD = 113) followed‐up (24 months).ResultsThe CDR‐FTLD demonstrated good consistency, construct and concurrent validity and correlated well with mini‐mental state examination (MMSE) and disease duration (ps < 0.05). At baseline, FTLD showed greater dementia severity than AD after matched for MMSE and disease duration (p < 0.001). Independent Rasch analyses demonstrated different patterns of progression for FTLD and AD in terms of the domains initially and then subsequently affected with disease progression. At follow‐up, although MMSE showed significant changes (p < 0.05), these were greater on the CDR‐FTLD (p < 0.001).ConclusionThe CDR‐FTLD satisfactorily measures dementia severity and change in FTLD, distinguishing disease progression between FTLD and AD, with clear implications for care, prognosis and future clinical trials. © 2016 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons, Ltd.

AbstractIntroductionThe Mediterranean diet (MeDi) is associated with reduced risk of cognitive impairment, but it is unclear whether it is associated with better brain imaging biomarkers.MethodsAmong 672 cognitively normal participants (mean age, 79.8 years, 52.5% men), we investigated associations of MeDi score and MeDi components with magnetic resonance imaging measures of cortical thickness for the four lobes separately and averaged (average lobar).ResultsHigher MeDi score was associated with larger frontal, parietal, occipital, and average lobar cortical thickness. Higher legume and fish intakes were associated with larger cortical thickness: legumes with larger superior parietal, inferior parietal, precuneus, parietal, occipital, lingual, and fish with larger precuneus, superior parietal, posterior cingulate, parietal, and inferior parietal. Higher carbohydrate and sugar intakes were associated with lower entorhinal cortical thickness.DiscussionIn this sample of elderly persons, higher adherence to MeDi was associated with larger cortical thickness. These cross‐sectional findings require validation in prospective studies.

Abstract Introduction Tau protein levels in plasma may be a marker of neuronal damage. We examined associations between plasma tau levels and Alzheimer's disease (AD)–related magnetic resonance imaging (MRI) and positron emission tomography (PET) neuroimaging measures among nondemented individuals. Methods Participants included 378 cognitively normal (CN) and 161 mild cognitive impairment (MCI) individuals enrolled in the Mayo Clinic Study of Aging with concurrent neuropsychological measures and amyloid PET, fluorodeoxyglucose PET, and MRI. Baseline plasma tau levels were measured using the Quanterix Simoa‐HD1 tau assay. Results Plasma tau levels were higher in MCI compared with CN (4.34 vs. 4.14 pg/mL, P = .078). In regression models adjusted for age, gender, education, and APOE , higher plasma tau was associated with worse memory performance (b = −0.30, P = .02) and abnormal cortical thickness in an AD signature region (odds ratio = 1.80, P = .018). Discussion Plasma tau is associated with cortical thickness and memory performance. Longitudinal studies will better elucidate the associations between plasma tau, neurodegeneration, and cognition.

One of the key research agenda of the field of aging is investigation of presymptomatic Alzheimer’s disease (AD). Furthermore, abnormalities in brain glucose metabolism (as measured by FDG-PET) have been reported among cognitively normal elderly persons. However, little is known about the association of FDG-PET abnormalities with neuropsychiatric symptoms (NPS) in a population-based setting. Thus, we conducted a cross-sectional study derived from the ongoing population-based Mayo Clinic Study of Aging in order to examine the association between brain glucose metabolism and NPS among cognitively normal (CN) persons aged > 70 years. Participants underwent FDG-PET and completed the Neuropsychiatric Inventory Questionnaire (NPI-Q), Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI). Cognitive classification was made by an expert consensus panel. We conducted multivariable logistic regression analyses to compute odds ratios (OR) and 95% confidence intervals after adjusting for age, sex, and education. For continuous variables, we used linear regression and Spearman rank-order correlations. Of 668 CN participants (median 78.1 years, 55.4% males), 205 had an abnormal FDG-PET (i.e., standardized uptake value ratio < 1.32 in AD-related regions). Abnormal FDG-PET was associated with depression as measured by NPI-Q (OR = 2.12; 1.23–3.64); the point estimate was further elevated for APOE ɛ 4 carriers (OR = 2.59; 1.00–6.69), though marginally significant. Additionally, we observed a significant association between abnormal FDG-PET and depressive and anxiety symptoms when treated as continuous measures. These findings indicate that NPS, even in community-based samples, can be an important additional tool to the biomarker-based investigation of presymptomatic AD.

Abstract Introduction The MAPT H1 haplotype has been associated with several neurodegenerative diseases. We were interested in exploring the role of MAPT haplotypic variation in risk of dementia with Lewy bodies (DLB). Method We genotyped six MAPT haplotype tagging SNPs and screened 431 clinical DLB cases, 347 pathologically defined high‐likelihood DLB cases, and 1049 controls. Result We performed haplotypic association tests and detected an association with the protective H2 haplotype in our combined series (odds ratio [OR] = 0.75). We fine‐mapped the locus and identified a relatively rare haplotype, H1G, that is associated with an increased risk of DLB (OR = 3.30, P = .0017). This association was replicated in our pathologically defined series (OR = 2.26, P = .035). Discussion These results support a role for H1 and specifically H1G in susceptibility to DLB. However, the exact functional variant at the locus is still unknown, and additional studies are warranted to fully explain genetic risk of DLB at the MAPT locus.