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INTRODUCTION: Cerebral small vessel disease (SVD) and amyloid beta (Aβ) pathology frequently co‐exist. The impact of concurrent pathology on the pattern of hippocampal atrophy, a key substrate of memory impacted early and extensively in dementia, remains poorly understood. METHODS: In a unique cohort of mixed Alzheimer's disease and moderate–severe SVD, we examined whether total and regional neuroimaging measures of SVD, white matter hyperintensities (WMH), and Aβ, as assessed by 18F‐AV45 positron emission tomography, exert additive or synergistic effects on hippocampal volume and shape. RESULTS: Frontal WMH, occipital WMH, and Aβ were independently associated with smaller hippocampal volume. Frontal WMH had a spatially distinct impact on hippocampal shape relative to Aβ. In contrast, hippocampal shape alterations associated with occipital WMH spatially overlapped with Aβ‐vulnerable subregions. DISCUSSION: Hippocampal degeneration is differentially sensitive to SVD and Aβ pathology. The pattern of hippocampal atrophy could serve as a disease‐specific biomarker, and thus guide clinical diagnosis and individualized treatment strategies for mixed dementia. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Plasma biomarkers are altered years prior to Alzheimer's disease (AD) clinical onset. METHODS: We measured longitudinal changes in plasma amyloid‐beta (Aβ)42/40 ratio, pTau181, pTau231, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) in a cohort of older adults at risk of AD (n = 373 total, n = 229 with Aβ and tau positron emission tomography [PET] scans) considering genetic and demographic factors as possible modifiers of these markers' progression. RESULTS: Aβ42/40 ratio concentrations decreased, while NfL and GFAP values increased over the 4‐year follow‐up. Apolipoprotein E (APOE) ε4 carriers showed faster increase in plasma pTau181 than non‐carriers. Older individuals showed a faster increase in plasma NfL, and females showed a faster increase in plasma GFAP values. In the PET subsample, individuals both Aβ‐PET and tau‐PET positive showed faster plasma pTau181 and GFAP increase compared to PET‐negative individuals. DISCUSSION: Plasma markers can track biological change over time, with plasma pTau181 and GFAP markers showing longitudinal change in individuals with preclinical AD. Highlights: Longitudinal increase of plasma pTau181 and glial fibrillary acidic protein (GFAP) can be measured in the preclinical phase of AD.Apolipoprotein E ε4 carriers experience faster increase in plasma pTau181 over time than non‐carriers.Female sex showed accelerated increase in plasma GFAP over time compared to males.Aβ42/40 and pTau231 values are already abnormal at baseline in individuals with both amyloid and tau PET burden. [ABSTRACT FROM AUTHOR]

Introduction: Prodromal markers of Alzheimer's disease (AD) have been derived from wakefulness. However, brain perfusion during rapid-eye movement (REM) sleep could be a sensitive marker of amnestic mild cognitive impairment (aMCI), as activation of REM sleep relies more on the cholinergic system.Methods: Eight subjects with aMCI, and 16 controls, underwent two single-photon emission computed tomography (SPECT) scans with tracer injected during REM sleep then wakefulness.Results: Perfusion in the anterior cingulate cortex was significantly decreased in aMCI cases compared to controls for both conditions. That defect was much larger and more severe in REM sleep (1795 voxels) compared to wakefulness (398 voxels), and extended to the middle cingulate cortex and the olfactory cortex. Hypoperfusion in the anterior cingulate cortex during REM sleep allowed better classification than hypoperfusion found in wakefulness (93.8 vs 81.3%).Conclusion: REM sleep imaging is a valuable tool with which to identify individuals at risk of developing AD. [ABSTRACT FROM AUTHOR]