White matter hyperintensities are higher among early‐onset Alzheimer's disease participants than their cognitively normal and early‐onset nonAD peers: Longitudinal Early‐onset Alzheimer's Disease Study (LEADS)

Abstract

INTRODUCTIONWe compared white matter hyperintensities (WMHs) in early‐onset Alzheimer's disease (EOAD) with cognitively normal (CN) and early‐onset amyloid‐negative cognitively impaired (EOnonAD) groups in the Longitudinal Early‐Onset Alzheimer's Disease Study.METHODSWe investigated the role of increased WMH in cognition and amyloid and tau burden. We compared WMH burden of 205 EOAD, 68 EOnonAD, and 89 CN participants in lobar regions using t‐tests and analyses of covariance. Linear regression analyses were used to investigate the association between WMH and cognitive impairment and that between amyloid and tau burden.RESULTSEOAD showed greater WMHs compared with CN and EOnonAD participants across all regions with no significant differences between CN and EOnonAD groups. Greater WMHs were associated with worse cognition. Tau burden was positively associated with WMH burden in the EOAD group.DISCUSSIONEOAD consistently showed higher WMH volumes. Overall, greater WMHs were associated with worse cognition and higher tau burden in EOAD.Highlights This study represents a comprehensive characterization of WMHs in sporadic EOAD. WMH volumes are associated with tau burden from positron emission tomography (PET) in EOAD, suggesting WMHs are correlated with increasing burden of AD. Greater WMH volumes are associated with worse performance on global cognitive tests. EOAD participants have higher WMH volumes compared with CN and early‐onset amyloid‐negative cognitively impaired (EOnonAD) groups across all brain regions.

Alcohol Use Disorder and Dementia: A Review

“… 281 , 282 As they are ubiquitous and heterogeneous, however, a better characterization of the extent, distribution, and cognitive correlates of WMH is necessary. 283 – 285 In support of a high co-occurrence of Alzheimer’s disease and vascular dementias, a literature review found a strong relationship between presence of amyloid and WMH burden 286 (also see Eloyan et al, 2023 287 ).…”

Neuropathology, Neuroimaging, and Fluid Biomarkers in Alzheimer’s Disease

“…(LEADS) [51]. A+EOAD showed greater severity of WMHs compared with CN and A-EOAD participants across all regions, with no significant differences between CN and A-EOAD participants.…”

“…In transgenic mice carrying the Presenilin-1 mutations, oligodendrocytes were sensitized to glutamate and amyloid toxicities, which exacerbated white matter damage and memory impairment in these mice [52]. The study by Eloyan et al (2023) suggests that the abnormalities of oligodendrocytes occur in the presence of a PS1 mutation. In conclusion, white matter disease is highly prevalent in AD patients, and both degenerative disease and vascular disease are associated with WMHs in AD, although the earliest changes in the white matter on MRI scans in AD patients appear to be related to the onset of neurodegenerative disease (Figure 2).…”

“…Eloyan et al (2023) compared the severity of (WMHs) between subjects with amyloidpositive early-onset Alzheimer's disease (A+EOAD) (n = 205) and individuals with normal cognition (CN) (n = 89) and individuals who were cognitively impaired but amyloidnegative EOAD (A-EOAD) in the Longitudinal Early-Onset Alzheimer's Disease Study (LEADS) [51]. A+EOAD showed greater severity of WMHs compared with CN and A-EOAD participants across all regions, with no significant differences between CN and A-EOAD participants.…”