MRI Visible Perivascular Spaces and the Risk of Incident Mild Cognitive Impairment in a Community Sample

Article type: Research Article

Authors: Pase, Matthew P.^{a; b; c; *} | Pinheiro, Adlin^{c; d} | Rowsthorn, Ella^a | Demissie, Serkalem^{c; d} | Hurmez, Saoresho^a | Aparicio, Hugo J.^{c; e} | Rodriguez-Lara, Frances^f | Gonzales, Mitzi M.^h | Beiser, Alexa^{c; d; e} | DeCarli, Charles^{c; g} | Seshadri, Sudha^{c; e; h} | Romero, Jose Rafael^{c; e; *}

Affiliations: [a] Turner Institute for Brain and Mental Health, Monash University, Clayton, Australia | [b] Harvard T.H. Chan School of Public Health, Boston, MA, USA | [c] NHLBI’s Framingham Heart Study, Framingham, MA, USA | [d] Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA | [e] Department of Neurology, Boston University School of Medicine, Boston, MA, USA | [f] Boston University School of Medicine, Boston, MA, USA | [g] Department of Neurology, University of California at Davis, Davis, CA, USA | [h] The Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases, University of Texas Health Sciences Center, San Antonio, TX, USA

Correspondence: [*] Correspondence to: Jose Rafael Romero, MD, Boston University School of Medicine, Boston, MA, USA. E-mail: joromero@bu.edu and Associate Professor Matthew Pase, PhD, 18 Innovation Walk, Monash University, Clayton, Victoria, Australia. E-mail: matthewpase@gmail.com.

Abstract: Background: Magnetic resonance imaging (MRI) visible perivascular spaces (PVS) are associated with the risk of incident dementia but their association with the early stages of cognitive impairment remains equivocal. Objective: We examined the association between MRI visible PVS and the risk of incident mild cognitive impairment (MCI) in the community-based Framingham Heart Study (FHS). Methods: FHS participants aged at least 50 years free of stroke, cognitive impairment, and dementia at the time of MRI were included. PVS were rated according to severity in the basal ganglia and centrum semiovale (CSO) using established criteria. Cox regression analyses were used to relate PVS to incident MCI adjusted for demographic and cardiovascular variables. Results: The mean age of the sample (1,314 participants) at MRI was 68 years (SD, 9; 54% women). There were 263 cases of incident MCI over a median 7.4 years follow-up (max, 19.8 years). MCI risk increased with higher PVS severity in the CSO. Relative to persons with the lowest severity rating, persons with the highest severity rating in the CSO had a higher risk of incident MCI (hazard ratio [HR] = 2.55; 95% confidence interval [CI], 1.48–4.37; p = 0.0007). In secondary analysis, this association seemed stronger in women. Risk of incident MCI was nominally higher for participants with the highest severity grade of PVS in the basal ganglia, though not statistically significant relative to the lowest grade (HR = 2.19; 95% CI, 0.78–6.14; p = 0.14). Conclusions: PVS burden in the CSO may be a risk marker for early cognitive impairment.

Keywords: Alzheimer’s disease, cerebral small vessel disease, magnetic resonance imaging, mild cognitive impairment, perivascular spaces

DOI: 10.3233/JAD-230445

Journal: Journal of Alzheimer's Disease, vol. 96, no. 1, pp. 103-112, 2023