Machulda, Mary M.

Background: Different clinical syndromes can arise from Alzheimer’s disease (AD) neuropathology, including dementia of the Alzheimer’s type (DAT), logopenic primary progressive aphasia (lvPPA), and posterior cortical atrophy (PCA). Objective: To assess similarities and differences in patterns of white matter tract degeneration across these syndromic variants of AD. Methods: Sixty-four subjects (22 DAT, 24 lvPPA, and 18 PCA) that had diffusion tensor imaging and showed amyloid-β deposition on PET were assessed in this case-control study. A whole-brain voxel-based analysis was performed to assess differences in fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity across groups. Results: All three groups showed overlapping diffusion abnormalities in a network of tracts, including fornix, corpus callosum, posterior thalamic radiations, superior longitudinal fasciculus, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, and uncinate fasciculus. Subtle regional differences were also observed across groups, with DAT particularly associated with degeneration of fornix and cingulum, lvPPA with left inferior fronto-occipital fasciculus and uncinate fasciculus, and PCA with posterior thalamic radiations, superior longitudinal fasciculus, posterior cingulate, and splenium of the corpus callosum. Conclusion: These findings show that while each AD phenotype is associated with degeneration of a specific structural network of white matter tracts, striking spatial overlap exists among the three network patterns that may be related to AD pathology.

AbstractIntroductionFew studies have examined the effects of amyloid and apolipoprotein E (APOE) genotype on cognition among middle‐aged individuals.MethodsWe included 464 cognitively normal, test‐naïve, participants with Pittsburgh compound B positron emission tomography amyloid imaging, mean age of 62.7 (range, 51–71 years), enrolled in the Mayo Clinic Study of Aging. Participants completed multiple cognitive assessments, including a standard neuropsychological battery and the CogState computerized battery, over 30 months of follow‐up. Linear mixed models were used to examine the effects of amyloid and APOE genotype on baseline cognition and cognitive decline.ResultsElevated amyloid was not associated with tests of episodic memory but did predict declines on tests of executive function. APOE genotype was not associated with cognition. Among APOE ɛ4 noncarriers, higher amyloid was predictive of decline on tests of executive function and on one episodic memory test.DiscussionElevated amyloidosis and APOE genotype do not appear to exert a dramatic influence on cognition in middle age.

Objectives To determine the association between multiple chronic conditions and risk of incident mild cognitive impairment ( MCI ) and dementia. Design Prospective cohort study. Setting Olmsted County, Minnesota. Participants Cognitively normal individuals (N = 2,176) enrolled in the Mayo Clinic Study of Aging ( MCSA ). Measurements Participants were randomly selected from the community, evaluated by a physician, and underwent neuropsychometric testing at baseline and at 15‐month intervals to assess diagnoses of MCI and dementia. Information on International Classification of Diseases, Ninth Revision codes for chronic conditions in the 5 years before enrollment was electronically captured using the Rochester Epidemiology Project medical records linkage system. Multimorbidity was defined as having two or more chronic conditions, and the association between multimorbidity and MCI and dementia was examined using Cox proportional hazards models. Results Of 2,176 cognitively normal participants (mean age ± standard deviation 78.5 ± 5.2; 50.6% male), 1,884 (86.6%) had multimorbidity. The risk of MCI or dementia was higher in persons with multimorbidity (hazard ratio ( HR ) = 1.38, 95% confidence interval ( CI ) = 1.05–1.82) than in those with one or no chronic condition. The HR was of greater magnitude in persons with four or more conditions ( HR = 1.61, 95% CI = 1.21–2.13) than in those with two or three conditions ( HR = 1.03, 95% CI = 0.76–1.39) and for men with multimorbidity( HR = 1.53, 95% CI = 1.01–2.31) than for women with multimorbidity ( HR = 1.20, 95% CI = 0.83–1.74), compared to those with one or no chronic condition. Conclusion In older adults, having multiple chronic conditions is associated with greater risk of MCI and dementia. This is consistent with the hypothesis that multiple etiologies may contribute to MCI and late‐life dementia. Preventing chronic diseases may be beneficial in delaying or preventing MCI and dementia.

Background and purpose A subset of patients with Alzheimer's disease ( AD ) present with early and prominent language impairment (aphasic AD ). Our previous study demonstrated an association between global β‐amyloid burden measured on [ 11 C] Pittsburgh compound B (PiB) positron emission tomography and general cognitive impairment, but not with aphasia, in such subjects. As a follow‐up, whether there is any association between regional β‐amyloid burden, atrophy on magnetic resonance imaging ( MRI ) and global cognitive impairment, aphasia or other cognitive and functional impairment in aphasic AD is assessed. Methods Forty‐four aphasic AD subjects who underwent PiB scanning and volumetric MRI and were determined to be positive for β‐amyloid deposition were analyzed. All had completed detailed neurological, neuropsychological and language batteries. Spearman's rank‐order correlation was utilized to assess for associations. Results Greater visuospatial impairment was associated with increased β‐amyloid burden in the primary visual cortex ( P = 0.001). Although there were many trends for associations between neurocognitive and language deficits and regional β‐amyloid burden, there were no strong associations that survived correction for multiple comparisons. However, neurocognitive and language impairment in these subjects strongly correlated with the degree of left lateral temporal and inferior parietal atrophy ( P < 0.004). Conclusions The findings from this study suggest a close relation between the severity of regional atrophy and cognitive and language impairment, but argue against a strong association between regional β‐amyloid burden and such deficits in aphasic AD subjects. Hence, other pathological factors may be driving the previously identified association between global β‐amyloid deposition and general cognitive impairment in aphasic AD .

AbstractIntroductionThe feasibility and validity of brief computerized cognitive batteries at the population‐level are unknown.MethodsNondemented participants (n = 1660, age 50–97 years) in the Mayo Clinic Study on Aging completed the computerized CogState battery and standard neuropsychological battery. The correlation between tests was examined and comparisons between CogState performance on the personal computer (PC) and iPad (n = 331), and in the clinic vs. at home (n = 194), were assessed.ResultsWe obtained valid data on greater than 97% of participants on each test. Correlations between the CogState and neuropsychological tests ranged from −0.462 to 0.531. Although absolute differences between the PC and iPad were small and participants preferred the iPad, performance on the PC was faster. Participants performed faster on Detection, One Card Learning, and One Back at home compared with the clinic.DiscussionThe computerized CogState battery, especially the iPad, was feasible, acceptable, and valid in the population.