Lowe, Val J.

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.

AbstractIntroductionThe objective of our study was to investigate cross‐sectional associations of atrial fibrillation with neuroimaging measures of cerebrovascular disease and Alzheimer's disease and their interactions with mild cognitive impairment (MCI).MethodsMagnetic resonance imaging scans of individuals from a population‐based study were analyzed for infarctions, total gray matter, and hippocampal and white matter hyperintensity volumes. A subsample underwent positron emission tomography imaging.ResultsAtrial fibrillation was associated with infarctions and lower total gray matter volume. Compared with subjects with no atrial fibrillation and no infarction, the odds ratio (95% confidence intervals) for MCI was 2.99 (1.57–5.70; P = .001) among participants with atrial fibrillation and infarction, 0.90 (0.45–1.80; P = .77) for atrial fibrillation and no infarction, and 1.50 (0.96–2.34; P = .08) for no atrial fibrillation and any infarction.DiscussionParticipants with both atrial fibrillation and infarction are more likely to have MCI than participants with either infarction or atrial fibrillation alone.

Background and objectives: We report a comprehensive clinical, radiological, neuropsychometric and pathological evaluation of a woman with a clinical diagnosis of AD dementia (ADem), but whose autopsy demonstrated widespread demyelination, without Alzheimer disease (AD) pathology. Methods and results: Initial neuropsychometric evaluation suggested amnestic mild cognitive impairment (aMCI). Serial magnetic resonance images (MRI) images demonstrated the rate of increase in her ventricular volume was comparable to that of 46 subjects with aMCI who progressed to ADem, without accumulating white matter disease. Myelin immunohistochemistry at autopsy demonstrated extensive cortical subpial demyelination. Subpial lesions involved the upper cortical layers, and often extended through the entire width of the cortex. Conclusions: Multiple sclerosis (MS) can cause severe cortical dysfunction and mimic ADem. Cortical demyelination is not well detected by standard imaging modalities and may not be detected on autopsy without myelin immunohistochemistry.

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 .