title: Subcortical Atrophy in Cognitive Impairment and Dementia.
abstract: BACKGROUND
  Cortical atrophy is a key neuroimaging feature of dementia. However, the role of subcortical gray matter reduction in cognitive impairment has not been explored extensively.
  
  
  OBJECTIVE
  We examined the risk factors of subcortical structures on neuroimaging and their association with cognitive impairment and dementia.
  
  
  METHODS
  Data from two studies were used: a subsample from the Epidemiology of Dementia in Singapore (EDIS) study of non-demented community-dwelling subjects (n = 550) and a case-control study. Subjects underwent similar neuropsychological tests and brain MRI. Subcortical volumes of accumbens, amygdala, caudate, pallidum, putamen, thalamus, hippocampus, and brainstem were measured. Cognitive impairment no dementia (CIND), dementia and its subtypes, vascular cognitive impairment (VCI), were defined using accepted criteria. Cognitive function was also expressed as both composite and domain-specific Z-scores.
  
  
  RESULTS
  In the EDIS study, age, female gender, Malay ethnicity, diabetes, lacunar-infarcts, and white matter lesions were the most important risk factors for subcortical atrophy. Moreover, smaller volumes of accumbens, amygdala, caudate, thalamus, and brainstem were significantly associated with lower cognitive composite Z-scores. With respect to clinical outcomes in the case-control study, structures such as the accumbens, caudate, putamen, and hippocampus were associated with both CIND and dementia. Smaller caudate and pallidum volumes were related to VCI whereas amygdalar atrophy was only associated with non-VCI. Furthermore, subcortical atrophy was related to both VCI and non-VCI.
  
  
  CONCLUSIONS
  Subcortical gray matter atrophy is not only observed in dementia, but also in the preclinical stages of cognitive impairment. Furthermore, besides VCI, subcortical structures were also related to non-VCI.
authors.affiliation: Memory Ageing and Cognition Centre (MACC), National University Health System, Singapore.|Department of Pharmacology, National University of Singapore, Singapore.
authors.forename: Saima
authors.initials: S
authors.lastname: Hilal
authors.affiliation: Memory Ageing and Cognition Centre (MACC), National University Health System, Singapore.|Department of Pharmacology, National University of Singapore, Singapore.
authors.forename: Shaik Muhammad
authors.initials: SM
authors.lastname: Amin
authors.affiliation: Raffles Neuroscience Centre, Raffles Hospital, Singapore.
authors.forename: Narayanaswamy
authors.initials: N
authors.lastname: Venketasubramanian
authors.affiliation: Departments of Radiology & Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands.|Faculty of Applied Sciences, Delft University of Technology, The Netherlands.
authors.forename: Wiro J
authors.initials: WJ
authors.lastname: Niessen
authors.affiliation: Departments of Radiology & Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Henri
authors.initials: H
authors.lastname: Vrooman
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Center, Singapore.|Academic Medicine Research Institute, Duke-NUS Graduate Medical School, Singapore.
authors.forename: Tien Yin
authors.initials: TY
authors.lastname: Wong
authors.affiliation: Memory Ageing and Cognition Centre (MACC), National University Health System, Singapore.|Department of Pharmacology, National University of Singapore, Singapore.
authors.forename: Christopher
authors.initials: C
authors.lastname: Chen
authors.affiliation: Memory Ageing and Cognition Centre (MACC), National University Health System, Singapore.|Department of Pharmacology, National University of Singapore, Singapore.|Singapore Eye Research Institute, Singapore National Eye Center, Singapore.|Academic Medicine Research Institute, Duke-NUS Graduate Medical School, Singapore.
authors.forename: Mohammad Kamran
authors.initials: MK
authors.lastname: Ikram
mesh_terms: D000368:Aged; D001284:Atrophy; D001921:Brain / Q000473:pathology*; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000473:pathology / Q000523:psychology; D016022:Case-Control Studies; D003071:Cognition; D003072:Cognition Disorders / Q000453:epidemiology / Q000473:pathology* / Q000523:psychology; D003704:Dementia / Q000453:epidemiology / Q000473:pathology* / Q000523:psychology; D005260:Female; D066128:Gray Matter / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D009929:Organ Size; D062706:Prodromal Symptoms; D012307:Risk Factors; D012846:Singapore / Q000453:epidemiology
keywords: Cognitive impairment; magnetic resonance imaging; risk factors; subcortical atrophy