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•What is the primary question addressed by this study? Do cognitive decline and social disengagement co-occur in cognitively normal older adults and are these changes related to brain amyloid-β, a pathologic marker of Alzheimer's disease?•What is the main finding of this study? In a longitudinal study of 217 community-dwelling, cognitively normal older adults, lower baseline social engagement was associated with steeper cognitive decline in those with higher amyloid-β levels. Lower-range but normal baseline cognitive performance was associated with decline in social engagement independent of amyloid-β level.•What is the meaning of the finding? Cognitive abilities and social function are related processes in older adults. Level of social engagement contributes to cognitive change in the high-risk group of older adults who are unimpaired but have evidence of Alzheimer's pathologic change.

•What is the primary question addressed by this study?Are there specific anxiety symptoms associated with Alzheimer's disease pathologies, amyloid-β and tau, in cognitively unimpaired older adults?•What is the main finding of this study?Greater amyloid-β deposition was associated with higher levels of self-reported worry but not global anxiety, independent of subjective and objective cognition and depression. No associations were found between regional tau deposition and either worry or global anxiety.•What is the meaning of the finding?These findings implicate worry as an early, specific behavioral marker and possible therapeutic target in preclinical AD.

Dorsal pathway dysfunctions are thought to underlie visuospatial processing problems in Alzheimer disease (AD). Prior studies reported compensatory mechanisms in the dorsal or ventral pathway in response to these functional changes. Since functional and structural connectivity are interrelated, these functional changes could be interpreted as a disconnection between both pathways. To better understand functional alterations in the dorsal pathway, we combined functional imaging with diffusion tensor imaging (DTI) in patients with mild cognitive impairment (MCI), a likely prodromal stage of AD.

Background:Recently, a new resting-state functional magnetic resonance imaging (rs-fMRI) measure to evaluate the concordance between different rs-fMRI metrics has been proposed and has not been investigated in Alzheimer's disease (AD).Methods:3T rs-fMRI data were obtained from healthy young controls (YC, n= 26), healthy senior controls (SC, n= 29), and AD patients (n= 35). The fractional amplitude of low-frequency fluctuations (fALFF), regional homogeneity (ReHo), and degree centrality (DC) were analyzed, followed by the calculation of their concordance using Kendall's W for each brain voxel across time. Group differences in the concordance were compared globally, within seven intrinsic brain networks, and on a voxel-by-voxel basis with covariates of age, sex, head motion, and gray matter volume.Results:The global concordance was lowest in AD among the three groups, with similar differences for the single metrics. When comparing AD to SC, reductions of concordance were detected in each of the investigated networks apart from the limbic network. For SC in comparison to YC, lower global concordance without any network-level difference was observed. Voxel-wise analyses revealed lower concordance in the right middle temporal gyrus in AD compared to SC and lower concordance in the left middle frontal gyrus in SC compared to YC. Lower fALFF were observed in the right angular gyrus in AD in comparison to SC, but ReHo and DC showed no group differences.Conclusions:The concordance of resting-state measures differentiates AD from healthy aging and may represent a novel imaging marker in AD.Impact statementThe usefulness of a new resting-state functional magnetic resonance imaging (rs-fMRI) measure to assess the concordance between different rs-fMRI metrics has been demonstrated in mental disorders such as depression and schizophrenia. Our study, to the best of our knowledge, is the first to confirm a decreased concordance in Alzheimer's disease (AD) patients compared to healthy young and senior individuals on global, network, and voxel-wise levels, which moreover seems to be sensitive in differentiating age-related from AD-related functional brain changes. Our findings suggest that the concordance of rs-fMRI metrics may be useful as a candidate biomarker for neurodegenerative disorders such as AD.

Background:Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is characterized by leukoencephalopathy leading to cognitive impairment. Subtle cognitive deficits can be observed early in the course of the disease, before the occurrence of the first stroke. Therefore, markers that can predict disease progression at this early stage, when interventions are likely to alter disease course, are needed. We aimed to examine the biological cascade of microstructural and macrostructural white matter (WM) abnormalities underlying cognitive deficits in CADASIL.Methods:We examined 20 nondemented CADASIL mutation carriers and 23 noncarriers who underwent neuropsychological evaluation and magnetic resonance imaging. Using probabilistic tractography of key WM tracts, we examined group differences in diffusivity measures and WM hyperintensity volume. Successive mediation models examined whether tract-specific WM abnormalities mediated subtle cognitive differences between CADASIL mutation carriers and noncarriers.Results:The largest effect size differentiating the two groups was observed for left superior longitudinal fasciculus–temporal (SLFt) diffusivity (Cohen's f= 0.49). No group differences were observed with a global diffusion measure. These specific microstructural differences in the SLFt were associated with higher WM hyperintensities burden, and subtle executive deficits in CADASIL mutation carriers.Discussion:Worse diffusivity in the left SLFt is related to greater severity of small vessel disease and worse executive functioning in the asymptomatic stage of the disease. Worse diffusivity of the left SLFt may potentially hold promise as an indicator of disease progression.