Small Vessel Disease and General Cognitive Function in Nondisabled Elderly

van der Flier, Wiesje M.; van Straaten, Elisabeth C.W.; Barkhof, Frederik; Verdelho, Ana; Madureira, Sofia; Pantoni, Leonardo; Inzitari, Domenico; Erkinjuntti, Timo; Crisby, Militta; Waldemar, Gunhild; Schmidt, Reinhold; Fazekas, Franz; Scheltens, Philip · 2005 · OpenAlex-citations

DOI: 10.1161/01.str.0000179092.59909.42

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Summary

This study investigates the independent contributions of white matter hyperintensities (WMH) and lacunes to general cognitive function in nondisabled elderly individuals. While small vessel disease is recognized as a predictor of cognitive decline and dementia, the specific clinical significance of these MRI markers—particularly their independent effects—had not been fully clarified. The research aimed to determine whether WMH and lacunes each uniquely impact cognitive performance in a population of independently living older adults. The analysis utilized baseline data from the multicenter, multinational Leukoaraiosis and Disability (LADIS) study, comprising 633 participants aged 65 to 84 years who had no or only mild disability in instrumental activities of daily living. General cognitive function was assessed using the Mini Mental State Examination (MMSE) and a modified Alzheimer Disease Assessment Scale (ADAS). MRI scans were centrally rated by a single rater blinded to clinical details. WMH severity was categorized as mild, moderate, or severe using the Fazekas scale, while lacunes were counted and categorized as none, few (1–3), or many (≥4). Statistical analysis employed general linear models to assess associations between these MRI markers and cognitive scores, correcting for confounders such as age, sex, education, depression, vascular risk factors, and stroke history. The results demonstrated that increasing severity of both WMH and lacunes was associated with deteriorating scores on both the MMSE and ADAS in basic analyses. When WMH and lacunes were entered simultaneously into multivariate models, both remained significantly associated with lower MMSE scores, indicating independent contributions to cognitive impairment. For the ADAS, increasing WMH severity remained significantly associated with worse performance, whereas the association with lacunes became less prominent, though it remained borderline significant. These associations persisted after adjusting for potential confounders, including center of origin and vascular risk factors. Additionally, the number of lacunes increased with the severity of WMH, though the correlation was moderate, supporting the view that they are distinct expressions of small vessel disease. The study concludes that WMH and lacunes are independently associated with general cognitive function in nondisabled elderly subjects. These findings highlight the clinical relevance of evaluating both MRI markers when assessing small vessel disease in relation to cognition. The authors suggest that while the study provides evidence for the importance of small vessel disease in cognitive impairment, future research using more specific cognitive tests and longitudinal designs is needed to determine causality and the full spectrum of cognitive decline.

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• cognitive impairment