title: Risk Factors and Consequences of Cortical Thickness in an Asian Population.
abstract: Cortical thickness has been suggested to be one of the most important markers of cortical atrophy. In this study, we examined potential risk factors of cortical thickness and its association with cognition in an elderly Asian population from Singapore. This is a cross-sectional study among 572 Chinese and Malay patients from the ongoing Epidemiology of Dementia in Singapore (EDIS) Study, who underwent comprehensive examinations including neuropsychological testing and brain magnetic resonance imaging (MRI). Cortical thickness (in micrometers) was measured using a model-based automated procedure. Cognitive function was expressed as composite and domain-specific Z-scores. Cognitive impairment was categorized into cognitive impairment no dementia (CIND)-mild, CIND-moderate, and dementia in accordance with accepted criteria. Linear regression models were used to examine the association between various risk factors and cortical thickness. With respect to cognition as outcome, both linear (for Z-scores) and logistic (for CIND/dementia) regression models were constructed. Initial adjustments were made for age, sex, and education, and subsequently for other cardiovascular risk factors and MRI markers. Out of 572 included patients, 171 (29.9%) were diagnosed with CIND-mild, 197 (34.4%) with CIND-moderate, and 28 (4.9%) with dementia. Risk factors related to a smaller cortical thickness were increased age, male sex, Malay ethnicity, higher blood glucose, and body mass index levels and presence of lacunar infarcts on MRI. Smaller cortical thickness was associated with CIND moderate/dementia [odds ratio (OR) per standard deviation (SD) decrease: 1.70; 95% confidence interval (CI): 1.19-2.44, P = 0.004] and with composite Z-score reflecting global cognitive functioning [mean difference per SD decrease: -0.094; 95% CI: -0.159; -0.030, P = 0.004]. In particular, smaller cortical thicknesses in the occipital and temporal lobes were related to cognitive impairment. Finally, in terms of specific cognitive domains, the most significant associations were found for executive function, visuoconstruction, and visual memory. Smaller cortical thickness is significantly associated with cognitive impairment, suggesting a contribution of diffuse cortical atrophy beyond the medial temporal lobe to cognitive function. These findings suggest that cortical thinning is a biomarker of neurodegenerative changes in the brain not only in dementia, but also in its preclinical stages.
authors.affiliation: From the Memory Ageing and Cognition Centre (MACC), National University Health System (SH, XX, SLA, CC, MKI); Department of Pharmacology, National University of Singapore (SH, XX, SLA, CC, MKI); Saw Swee Hock School of Public Health, National University of Singapore (CST); Raffles Neuroscience Centre, Raffles Hospital, Singapore (NV); Departments of Radiology and Medical Informatics, Erasmus University Medical Center, Rotterdam (WJN, HV); Faculty of Applied Sciences, Delft University of Technology, Delft, The Netherlands (WJN); Singapore Eye Research Institute, Singapore National Eye Center, Singapore (TYW, MKI); Academic Medicine Research Institute, Duke-NUS Graduate Medical School, Singapore (TYW, MKI); Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, The Netherlands (MKI).
authors.forename: Saima
authors.initials: S
authors.lastname: Hilal
authors.forename: Xu
authors.initials: X
authors.lastname: Xin
authors.forename: Seow Li
authors.initials: SL
authors.lastname: Ang
authors.forename: Chuen Seng
authors.initials: CS
authors.lastname: Tan
authors.forename: Narayanaswamy
authors.initials: N
authors.lastname: Venketasubramanian
authors.forename: Wiro J
authors.initials: WJ
authors.lastname: Niessen
authors.forename: Henri
authors.initials: H
authors.lastname: Vrooman
authors.forename: Tien Yin
authors.initials: TY
authors.lastname: Wong
authors.forename: Christopher
authors.initials: C
authors.lastname: Chen
authors.forename: Mohammad Kamran
authors.initials: MK
authors.lastname: Ikram
mesh_terms: D000368:Aged; D044466:Asian People; D002540:Cerebral Cortex / Q000473:pathology*; D003072:Cognition Disorders / Q000453:epidemiology / Q000473:pathology*; D003430:Cross-Sectional Studies; D003704:Dementia / Q000453:epidemiology / Q000473:pathology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009929:Organ Size; D012307:Risk Factors; D012846:Singapore