Regional White Matter Hyperintensities and Alzheimer’s Disease Biomarkers Among Older Adults with Normal Cognition and Mild Cognitive Impairment

Abstract

Background: Alzheimer’s disease (AD) frequently co-occurs with other brain pathologies. Recent studies suggest there may be a mechanistic link between AD and small vessel cerebrovascular disease (CVD), as opposed to simply the overlap of two disorders. Objective: We investigated the cross-sectional relationship between white matter hyperintensity (WMH) volumes (markers of CVD) and cerebrospinal fluid (CSF) biomarkers of AD. Methods: WMH volumes were assessed globally and regionally (i.e., frontal, parietal, temporal, occipital, and limbic). CSF AD biomarkers (i.e., Aβ 40, Aβ 42, Aβ 42/Aβ 40 ratio, phosphorylated tau-181 [p-tau181], and total tau [t-tau]) were measured among 152 non-demented individuals (134 cognitively unimpaired and 18 with mild cognitive impairment (MCI)). Results: Linear regression models showed that among all subjects, higher temporal WHM volumes were associated with AD biomarkers (higher levels of p-tau181, t-tau, and Aβ 40), particularly among APOE ɛ 4 carriers (independent of Aβ 42 levels). Higher vascular risk scores were associated with greater parietal and frontal WMH volumes (independent of CSF AD biomarker levels). Among subjects with MCI only, parietal WMH volumes were associated with a lower level of Aβ 42/Aβ 40. In addition, there was an association between higher global WMH volumes and higher CSF t-tau levels among younger participants versus older ones (∼<65 versus 65+ years), independent of Aβ 42/Aβ 40 and p-tau181. Conclusion: These findings suggest that although WMH are primarily related to systemic vascular risk and neurodegeneration (i.e., t-tau), AD-specific pathways may contribute to the formation of WMH in a regionally-specific manner, with neurofibrillary tangles (i.e., p-tau) playing a role in temporal WMHs and amyloid (i.e., Aβ 42/Aβ 40) in parietal WMHs.

Sleep and physical activity measures are associated with resting-state network segregation in non-demented older adults

“…These factors encompass hypertension, hypercholesterolemia, current smoking within the last 30 days, obesity (i.e., measured body mass index of 30 kg/m 2 or higher), and diabetes. The vascular risk summary score has been shown to predict dementia incidence ( Gottesman et al, 2017 ) and been used in a number of prior studies ( Newton et al, 2023 , Pettigrew et al, 2020 , Soldan et al, 2020 ). Data for vascular risk factors were obtained at the same visit as the MRI scan.…”

Therapeutic potential of mesenchymal stem cells for cerebral small vessel disease

“…The combination of TSA and MSCs has been found to improve learning and memory function in 4-VO rats by inhibiting the apoptosis of hippocampal neurons, reducing tau phosphorylation and enhancing central cholinergic system activity [ 142 ]. Tau phosphorylation may contribute to regional WMHs, the marker of CSVD, in AD patients [ 143 ].…”

Grey Matters: The Unique Landscape of Depression Treatment in Older Adults

“…Linking this to other neurodegenerative disorders is the fact that WHM is also a well-established predictor of dementia, as well as cerebrovascular events overall (Debette & Markus, 2010). Increased WHM can generally be considered an indicator of both vascular risks and cognitive decline (Newton et al, 2023). Therefore, it can be reasonably hypothesized that the existence of WMH may indicate the presence of small-vessel cerebrovascular diseases that can cause, be caused by, or have reciprocal relationships with the cognitive and affective impairments seen in both LLD and dementia (Butters et al, 2008;Brickman et al, 2009 2019).…”