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Abstract
Objective To investigate the relationship between enlarged perivascular spaces (EPVS) and measures of Alzheimer disease (AD), small vessel disease (SVD), cognition, vascular risk factors, and neuroinflammation, we tested associations between EPVS and different relevant neuroimaging, biochemical, and cognitive variables in 778 study participants.
Methods Four hundred ninety-nine cognitively unimpaired (CU) individuals, 240 patients with mild cognitive impairment, and 39 patients with AD from the Swedish Biomarkers for Identifying Neurodegenerative Disorders Early and Reliably (BioFINDER) study were included. EPVS with diameter >1 mm in centrum semiovale (CSO), basal ganglia (BG), and hippocampus (HP); hippocampal volume; white matter lesions (WML); and other SVD markers were determined from MRI. CSF levels of β-amyloid42 (Aβ42), phosphorylated tau, total tau, and neuroinflammatory markers; amyloid accumulation determined with [18F]-flutemetamol PET; and vascular risk factors and results from cognitive tests were determined and collected.
Results EPVS in CSO, BG, and HP were associated with WML volume and Fazekas score in individuals without dementia. No associations were found between EPVS and CSF Aβ42, total tau and phosphorylated tau, neuroinflammatory markers, vascular risk factors, and cognitive tests. EPVS in HP were associated with hippocampal atrophy. In a matched group of individuals with AD and CU, EPVS in HP were associated with AD diagnosis.
Conclusions EPVS are related to SVD, also in early disease stages, but the lack of correlation with cognition suggests that their importance is limited. Our data do not support a role for EPVS in early AD pathogenesis.
Glossary
- Aβ=
- β-amyloid;
- AD=
- Alzheimer disease;
- ADAS=
- Alzheimer's Disease Assessment Scale;
- AQT=
- A Quick Test of Cognitive Speed;
- BG=
- basal ganglia;
- BioFINDER=
- Biomarkers for Identifying Neurodegenerative Disorders Early and Reliably;
- CI=
- confidence interval;
- CMB=
- cerebral microbleed;
- CSO=
- centrum semiovale;
- CU=
- cognitively unimpaired;
- EPVS=
- enlarged perivascular spaces;
- FLAIR=
- fluid-attenuated inversion recovery;
- HP=
- hippocampus;
- IHD=
- ischemic heart disease;
- MCI=
- mild cognitive impairment;
- MMSE=
- Mini-Mental State Examination;
- MPRAGE=
- magnetization-prepared rapid gradient echo;
- OR=
- odds ratio;
- SCD=
- subjective cognitive decline;
- SE=
- standard error;
- SVD=
- small vessel disease;
- TMT=
- Trail-Making Test;
- TMTA=
- TMT Part A;
- WML=
- white matter lesions
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
↵* These authors contributed equally to this work as first authors.
↵† These authors contributed equally to this work as senior authors.
- Received January 15, 2020.
- Accepted in final form August 28, 2020.
- © 2020 American Academy of Neurology
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