{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T19:22:59Z","timestamp":1784229779897,"version":"3.55.0"},"reference-count":39,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:00:00Z","timestamp":1760400000000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000957","name":"Alzheimer's Association","doi-asserted-by":"publisher","award":["AACSF\u201021 \u2010723015"],"award-info":[{"award-number":["AACSF\u201021 \u2010723015"]}],"id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004375","name":"Tel Aviv University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004375","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010661","name":"Horizon 2020 Framework Programme","doi-asserted-by":"publisher","award":["MES\u2010CoBraD\u201d (H2020\u2010SC1\u2010BHC\u20102018\u20102020 \/ GA 965422)"],"award-info":[{"award-number":["MES\u2010CoBraD\u201d (H2020\u2010SC1\u2010BHC\u20102018\u20102020 \/ GA 965422)"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp; Dementia"],"published-print":{"date-parts":[[2025,10]]},"abstract":"Abstract<\/jats:title>\n \n BACKGROUND<\/jats:title>\n This study assessed the impact of cerebral small vessel disease (CSVD) on cognition in individuals with early\u2010onset (EO;\u00a0<65 years) and late\u2010onset (LO; \u226565 years) cognitive complaints.<\/jats:p>\n <\/jats:sec>\n \n METHODS<\/jats:title>\n Participants underwent prospective evaluations including cognitive testing, hyperphosphorylated tau\u2010217 (p\u2010tau217) and neurofilament\u2010light\u2010chain (NfL), and magnetic resonance imaging (MRI). Each CSVD marker was modeled for interaction with group age on results on cognitive outcomes: Montreal Cognitive Assessment (MoCA), Mini\u2010Mental State Examination (MMSE), Neuropsychiatric Inventory Questionnaire (NPI\u2010Q), and Clinical Dementia Rating (CDR) scale plus National Alzheimer's Coordinating Center\u2013Frontotemporal Lobar Degeneration module (NACC\u2010FTLD).<\/jats:p>\n <\/jats:sec>\n \n RESULTS<\/jats:title>\n \n Altogether, 168 patients (91 EO) were included. white matter hyperintensity (WMH) volume was associated with worse CDR+NACC\u2010FTLD in EO (\n \u03b2\u00a0<\/jats:italic>\n =\u00a017.8,\n p\u00a0<\/jats:italic>\n =\u00a00.013), remaining significant after adjusting for p\u2010tau217 and NfL, but not gray matter atrophy. Lacunes were associated with worse CDR plus NACC\u2010FTLD in EO (\n \u03b2\u00a0<\/jats:italic>\n =\u00a04.3,\n p\u00a0<\/jats:italic>\n =\u00a00.011), with age\u2010dependent associations with MoCA, MMSE, CDR\u00a0+\u00a0NACC\u2010FTLD, and NPI\u2010Q (\n p<\/jats:italic>\n \u00a0\u00a0<\u00a0\u00a00.01).\n <\/jats:p>\n <\/jats:sec>\n \n DISCUSSION<\/jats:title>\n CSVD markers, although less prevalent in EO, had greater clinical impact. These findings highlight an increased vulnerability to vascular pathology in EO patients and the importance of early detection.<\/jats:p>\n <\/jats:sec>\n \n Highlights<\/jats:title>\n \n \n \n Cerebral small vessel disease (CSVD) markers were more impactful in early\u2010onset than late\u2010onset dementia.<\/jats:p>\n <\/jats:list-item>\n \n White matter hyperintensity (WMH) volume predicted functional decline in early onset, independent of neurodegeneration.<\/jats:p>\n <\/jats:list-item>\n \n Lacunes showed age\u2010dependent effects on multiple cognitive outcomes.<\/jats:p>\n <\/jats:list-item>\n \n Findings support early detection of CSVD in younger individuals with dementia.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n 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