Vemuri, Prashanthi

AbstractIntroductionWe examined differences in cortical thickness in empirically derived mild cognitive impairment (MCI) subtypes in the Mayo Clinic Study of Aging.MethodsWe compared cortical thickness of four incident MCI subtypes (n = 192) to 1257 cognitive unimpaired individuals.ResultsThe subtle cognitive impairment cluster had atrophy in the entorhinal and parahippocampal cortex. The amnestic, dysnomic, and dysexecutive clusters also demonstrated entorhinal cortex atrophy as well as thinning in temporal, parietal, and frontal isocortex in somewhat different patterns.DiscussionWe found patterns of atrophy in each of the incident MCI clusters that corresponded to their patterns of cognitive impairment. The identification of MCI subtypes based on cognitive and structural features may allow for more efficient trial and study designs. Given individuals in the subtle cognitive impairment cluster have less structural changes and cognitive decline and may represent the earliest group, this could be a unique group to target with early interventions.

AbstractObjectiveTo examine the association of baseline elevated brain amyloid and neurodegeneration with changes in activities of daily living in participants without dementia (ND; i.e., cognitively unimpaired and participants with mild cognitive impairment) at baseline in the population‐based Mayo Clinic Study of Aging.MethodsWe included 1747 ND participants with 11C‐PiB PET and MR imaging in the study, with data on activities of daily living (as assessed by the Functional Activities Questionnaire (FAQ) and the Clinical Dementia Rating scale Sum of Boxes for functional domains (CDR‐SOB (functional)), with a median (range) of 4.3 (0.0–12.7) years of follow‐up. Abnormal (elevated; A+) 11C‐PiB‐PET retention ratio was defined as standardized uptake value ratio ≥ 1.48, and abnormal (reduced) AD signature cortical thickness as ≤ 2.68 mm (neurodegeneration; N+). Associations were examined with mixed effects models, adjusting for age, sex, education, apolipoprotein E ε4 allele carrier status, and global cognitive z‐score.ResultsMean age (SD) was 71.4 years (10.1), 46.7% were females, 195 (11.2%) had A+N‐, 442 (25.3%) had A‐N+, and 339 (19.4%) had A+N+ biomarkers. The A+N+ group had the largest annualized change in the FAQ score from baseline (difference in annual change A+N+ vs. A‐N‐; ß (SE): 0.80 (0.07)); associations were substantially attenuated when a time‐varying global cognitive composite was included in the model (A+N+ vs. A‐N‐; ß (SE): 0.31 (0.05)). CDR‐SOB (functional) findings partly agreed with FAQ score findings.InterpretationThe longitudinal increase in functional limitations is greater for individuals with abnormal neuroimaging biomarkers, especially for those with both elevated brain amyloid and neurodegeneration.

ObjectiveTo investigate β‐amyloid and tau depositions using Pittsburgh compound B (PiB) positron emission tomography (PET) and AV1451 tau PET imaging in aging multiple sclerosis (MS) patients.MethodsPatients with MS (n = 16) and controls (n = 80) matched for age, sex, andAPOEε4 status from the population‐based Mayo Clinic Study of Aging who underwent PiB PET imaging were studied. Of these individuals, 12 patients with MS and 60 matching controls also underwent AV1451 tau PET. Cortical PiB and AV1451 standard uptake value ratios (SUVrs) from the entire cortex and previously determined Alzheimer disease (AD) signature regions in the same population were calculated for group comparisons and testing for associations with age.ResultsAD signature PiB SUVr (odds ratio [OR] [95% confidence interval (CI)] = 0.52 [0.27–0.98],p= 0.044), total cortical PiB SUVr (OR [95% CI] = 0.52 [0.28–0.99],p= 0.048), and the frequency of abnormal PiB SUVrs (OR [95% CI] = 0.10 [0.01–0.90],p= 0.040) were lower in MS than controls. Although AD‐signature and total cortical AV1451 SUVrs were not different between the groups, the frequency of abnormal AV1451 SUVrs was higher (OR [95% CI] = 10.65 [1.10–103.35],p= 0.041) in MS than controls. The association of AD signature PiB SUVr with age was steeper in the controls compared to patients with MS (estimate [95% CI] = −0.14 [−0.023 to −0.006],p= 0.002). Similarly, the association of total cortical PiB SUVr with age was steeper in the controls compared to patients with MS (estimate [95% CI] = −0.13 [−0.021 to −0.005],p= 0.002). There was no difference in the association of AV1451 SUVr findings with age between the MS patients and controls.InterpretationAlthough both β‐amyloid and tau are biomarkers of cognitive aging and AD, cortical β‐amyloid deposition was lower in MS than age‐matched controls, suggesting that some aspect of MS pathobiology retards the accumulation of β‐amyloid but not the accumulation of tau.ANN NEUROL 2020;87:556–567