Saima Hilal1, Chuen Seng Tan1, Hieab H H Adams1, Mohamad Habes1, Vincent Mok1, Narayanaswamy Venketasubramanian1, Edith Hofer1, M Kamran Ikram1, Jill Abrigo1, Meike W Vernooij1, Christopher Chen1, Norbert Hosten1, Henry Volzke1, Hans J Grabe1, Reinhold Schmidt1, M Arfan Ikram2. 1. From the Departments of Radiology and Nuclear Medicine (S.H., H.H.H.A., M.W.V., M.A.I.), Epidemiology (S.H., H.H.H.A., M.K.I., M.W.V., M.A.I.), and Neurology (M.K.I., M.A.I.), Erasmus Medical Center, Rotterdam, the Netherlands; Department of Pharmacology (S.H., C.C.), National University of Singapore; Memory, Aging and Cognition Center (S.H., C.C.), National University Health System; Saw Swee Hock School of Public Health (C.S.T.), National University of Singapore; Department of Radiology (M.H.), University of Pennsylvania, Philadelphia; Department of Psychiatry and Psychotherapy (M.H., H.J.G.), Institute for Community Medicine (M.H., H.V., H.J.G.), and Institute of Diagnostic Radiology and Neuroradiology (N.H.), University Medicine Greifswald, Germany; Therese Pei Fong Chow Research Center for Prevention of Dementia (V.M.), LuiChe Woo Institute of Innovative Medicine, Gerald Choa Neuroscience Centre; Department of Medicine and Therapeutics (V.M.) and Department of Imaging & Interventional Radiology (J.A.), Chinese University of Hong Kong, China; Raffles Neuroscience Centre (N.V.), Raffles Hospital, Singapore; Department of Neurology (E.H.), Medical University of Graz, Austria; and German Center for Neurodegenerative Diseases (DZNE) (R.S.), Site Rostock/Greifswald, Germany. 2. From the Departments of Radiology and Nuclear Medicine (S.H., H.H.H.A., M.W.V., M.A.I.), Epidemiology (S.H., H.H.H.A., M.K.I., M.W.V., M.A.I.), and Neurology (M.K.I., M.A.I.), Erasmus Medical Center, Rotterdam, the Netherlands; Department of Pharmacology (S.H., C.C.), National University of Singapore; Memory, Aging and Cognition Center (S.H., C.C.), National University Health System; Saw Swee Hock School of Public Health (C.S.T.), National University of Singapore; Department of Radiology (M.H.), University of Pennsylvania, Philadelphia; Department of Psychiatry and Psychotherapy (M.H., H.J.G.), Institute for Community Medicine (M.H., H.V., H.J.G.), and Institute of Diagnostic Radiology and Neuroradiology (N.H.), University Medicine Greifswald, Germany; Therese Pei Fong Chow Research Center for Prevention of Dementia (V.M.), LuiChe Woo Institute of Innovative Medicine, Gerald Choa Neuroscience Centre; Department of Medicine and Therapeutics (V.M.) and Department of Imaging & Interventional Radiology (J.A.), Chinese University of Hong Kong, China; Raffles Neuroscience Centre (N.V.), Raffles Hospital, Singapore; Department of Neurology (E.H.), Medical University of Graz, Austria; and German Center for Neurodegenerative Diseases (DZNE) (R.S.), Site Rostock/Greifswald, Germany. m.a.ikram@erasmusmc.nl.
Abstract
OBJECTIVE: To investigate the association of enlarged perivascular spaces (ePVS) with cognition in elderly without dementia. METHODS: We included 5 studies from the Uniform Neuro-Imaging of Virchow-Robin Space Enlargement (UNIVRSE) consortium, namely the Austrian Stroke Prevention Family Study, Study of Health in Pomerania, Rotterdam Study, Epidemiology of Dementia in Singapore study, and Risk Index for Subclinical Brain Lesions in Hong Kong study. ePVS were counted in 4 regions (mesencephalon, hippocampus, basal ganglia, and centrum semiovale) with harmonized rating across studies. Mini-Mental State Examination (MMSE) and general fluid cognitive ability factor (G-factor) were used to assess cognitive function. For each study, a linear regression model was performed to estimate the effect of ePVS on MMSE and G-factor. Estimates were pooled across studies with the use of inverse variance meta-analysis with fixed- or random-effect models when appropriate. RESULTS: The final sample size consisted of 3,575 persons (age range 63.4-73.2 years, 50.6% women). Total ePVS counts were not significantly associated with MMSE score (mean difference per ePVS score increase 0.001, 95% confidence interval [CI] -0.007 to 0.008, p = 0.885) or G-factor (mean difference per ePVS score increase 0.002, 95% CI -0.001 to 0.006, p = 0.148) in age-, sex-, and education-adjusted models. Adjustments for cardiovascular risk factors and MRI markers did not change the results. Repeating the analyses with region-specific ePVS rendered similar results. CONCLUSIONS: In this study, we found that ePVS counts were not associated with cognitive dysfunction in the general population. Future studies with longitudinal designs are warranted to examine whether ePVS contribute to cognitive decline.
OBJECTIVE: To investigate the association of enlarged perivascular spaces (ePVS) with cognition in elderly without dementia. METHODS: We included 5 studies from the Uniform Neuro-Imaging of Virchow-Robin Space Enlargement (UNIVRSE) consortium, namely the Austrian Stroke Prevention Family Study, Study of Health in Pomerania, Rotterdam Study, Epidemiology of Dementia in Singapore study, and Risk Index for Subclinical Brain Lesions in Hong Kong study. ePVS were counted in 4 regions (mesencephalon, hippocampus, basal ganglia, and centrum semiovale) with harmonized rating across studies. Mini-Mental State Examination (MMSE) and general fluid cognitive ability factor (G-factor) were used to assess cognitive function. For each study, a linear regression model was performed to estimate the effect of ePVS on MMSE and G-factor. Estimates were pooled across studies with the use of inverse variance meta-analysis with fixed- or random-effect models when appropriate. RESULTS: The final sample size consisted of 3,575 persons (age range 63.4-73.2 years, 50.6% women). Total ePVS counts were not significantly associated with MMSE score (mean difference per ePVS score increase 0.001, 95% confidence interval [CI] -0.007 to 0.008, p = 0.885) or G-factor (mean difference per ePVS score increase 0.002, 95% CI -0.001 to 0.006, p = 0.148) in age-, sex-, and education-adjusted models. Adjustments for cardiovascular risk factors and MRI markers did not change the results. Repeating the analyses with region-specific ePVS rendered similar results. CONCLUSIONS: In this study, we found that ePVS counts were not associated with cognitive dysfunction in the general population. Future studies with longitudinal designs are warranted to examine whether ePVS contribute to cognitive decline.
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