Dataset Information

Cerebrospinal fluid ?-amyloid42 and neurofilament light relate to white matter hyperintensities.

ABSTRACT: White matter hyperintensities (WMHs) are associated with poorer brain health, but their pathophysiological substrates remain elusive. To better understand the mechanistic underpinnings of WMHs among older adults, this study examined in vivo cerebrospinal fluid biomarkers of ?-amyloid42 deposition (A?42), hyperphosphorylated tau pathology, neurodegeneration (total tau), and axonal injury (neurofilament light [NFL]) in relation to log-transformed WMHs volume. Participants free of clinical stroke and dementia were drawn from the Vanderbilt Memory & Aging Project (n = 148, 72 ± 6 years). Linear regression models adjusted for age, sex, race/ethnicity, education, intracranial volume, modified Framingham Stroke Risk Profile (excluding points assigned for age), cognitive diagnosis, and APOE-?4 carrier status. A?42 (? = -0.001, p = 0.007) and NFL (? = 0.0003, p = 0.01) concentrations related to WMHs but neither hyperphosphorylated tau nor total tau associations with WMHs reached statistical significance (p-values > 0.21). In a combined model, NFL accounted for 3.2% of unique variance in WMHs and A?42 accounted for an additional 4.3% beyond NFL, providing novel evidence of the co-occurrence of at least 2 distinct pathways for WMHs among older adults, including amyloid deposition and axonal injury.

SUBMITTER: Osborn KE

PROVIDER: S-EPMC6085839 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Cerebrospinal fluid β-amyloid42 and neurofilament light relate to white matter hyperintensities.

Osborn Katie E KE Liu Dandan D Samuels Lauren R LR Moore Elizabeth E EE Cambronero Francis E FE Acosta Lealani Mae Y LMY Bell Susan P SP Babicz Michelle A MA Gordon Elizabeth A EA Pechman Kimberly R KR Davis L Taylor LT Gifford Katherine A KA Hohman Timothy J TJ Blennow Kaj K Zetterberg Henrik H Jefferson Angela L AL

Neurobiology of aging 20180403

White matter hyperintensities (WMHs) are associated with poorer brain health, but their pathophysiological substrates remain elusive. To better understand the mechanistic underpinnings of WMHs among older adults, this study examined in vivo cerebrospinal fluid biomarkers of β-amyloid42 deposition (Aβ42), hyperphosphorylated tau pathology, neurodegeneration (total tau), and axonal injury (neurofilament light [NFL]) in relation to log-transformed WMHs volume. Participants fre ...[more]

PMID: 29702372

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Project description:Cerebral small vessel diseases play a crucial role in both vascular and non-vascular dementias. The location of white matter hyperintensities (WMHs), a neuroimaging marker of cerebral small vessel disease, has been found to vary between different types of dementias, and those in the basal ganglia (BG) have been particularly associated with vascular cognitive impairment (VCI). However, anatomical variation of WMHs across BG nuclei and its effect on brain network dysconnectivity has not been clearly elucidated. The study sample consisted of 40 patients with amnestic mild cognitive impairment (aMCI), 40 with subcortical vascular MCI (SVMCI), and 40 healthy control subjects. We examined the volume of WMH using T2-weighted magnetic resonance imaging. We also assessed the disturbances in BG-cortical communication by measuring resting-state functional connectivity (rsFC) from the functional magnetic resonance imaging signal. WMHs were more pronounced in the SVMCI group particularly in the caudate regions. In SVMCI patients, while higher WMHs in the dorsal caudate correlated with weaker FC with executive control regions and worse immediate recall performance, WMHs in the ventral caudate were associated with weaker FC with anterior default mode regions and worse delayed recall performance. In contrast, in aMCI patients, BG WMHs were not correlated with their changes in functional connectivity changes, which showed weaker connectivity with almost all BG structures, rather than restricting to specific BG subdivisions as observed in the SVMCI group. Our findings demonstrate that heterogeneously distributed BG WMHs are associated with changes in functional network interactions and verbal episodic memory performance only in SVMCI patients, which establishes a link between cerebrovascular-related structural abnormality, functional integrity of BG circuits, and episodic memory impairments in SVMCI, and may reflect a differential role of the cerebrovascular pathology in disrupting network-level communications and cognition between Alzheimer's and subcortical vascular dementia.

Dataset Information

Cerebrospinal fluid ?-amyloid42 and neurofilament light relate to white matter hyperintensities.

Publications

Cerebrospinal fluid β-amyloid<sub>42</sub> and neurofilament light relate to white matter hyperintensities.

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