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Vascular burden and cognition: Mediating roles of neurodegeneration and amyloid PET
Author(s) -
Ottoy Julie,
Ozzoude Miracle,
Zukotynski Katherine,
Adamo Sabrina,
Scott Christopher,
Gaudet Vincent,
Ramirez Joel,
Swardfager Walter,
CogoMoreira Hugo,
Lam Benjamin,
Bhan Aparna,
Mojiri Parisa,
Kang Min Su,
Rabin Jennifer S.,
Kiss Alex,
Strother Stephen,
Bocti Christian,
Borrie Michael,
Chertkow Howard,
Frayne Richard,
Hsiung Robin,
Laforce Robert Jr.,
Noseworthy Michael D.,
Prato Frank S.,
Sahlas Demetrios J.,
Smith Eric E.,
Kuo Phillip H.,
Sossi Vesna,
Thiel Alexander,
Soucy JeanPaul,
Tardif JeanClaude,
Black Sandra E.,
Goubran Maged
Publication year - 2023
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.12750
Subject(s) - neurodegeneration , hyperintensity , cognition , atrophy , psychology , neuroscience , cognitive decline , white matter , episodic memory , temporal lobe , alzheimer's disease , pathology , medicine , dementia , disease , magnetic resonance imaging , epilepsy , radiology
It remains unclear to what extent cerebrovascular burden relates to amyloid beta (Aβ) deposition, neurodegeneration, and cognitive dysfunction in mixed disease populations with small vessel disease and Alzheimer's disease (AD) pathology. In 120 subjects, we investigated the association of vascular burden (white matter hyperintensity [WMH] volumes) with cognition. Using mediation analyses, we tested the indirect effects of WMH on cognition via Aβ deposition ( 18 F‐AV45 positron emission tomography [PET]) and neurodegeneration (cortical thickness or 18 F fluorodeoxyglucose PET) in AD signature regions. We observed that increased total WMH volume was associated with poorer performance in all tested cognitive domains, with the strongest effects observed for semantic fluency. These relationships were mediated mainly via cortical thinning, particularly of the temporal lobe, and to a lesser extent serially mediated via Aβ and cortical thinning of AD signature regions. WMH volumes differentially impacted cognition depending on lobar location and Aβ status. In summary, our study suggests mainly an amyloid‐independent pathway in which vascular burden affects cognitive function via localized neurodegeneration. Highlights Alzheimer's disease often co‐exists with vascular pathology. We studied a unique cohort enriched for high white matter hyperintensities (WMH). High WMH related to cognitive impairment of semantic fluency and executive function. This relationship was mediated via temporo‐parietal atrophy rather than metabolism. This relationship was, to lesser extent, serially mediated via amyloid beta and atrophy.