Subcortical Atrophy in Cognitive Impairment and Dementia

Article type: Research Article

Authors: Hilal, Saima^{a; b} | Amin, Shaik Muhammad^{a; b} | Venketasubramanian, Narayanaswamy^c | Niessen, Wiro J.^{d; e} | Vrooman, Henri^d | Wong, Tien Yin^{f; g} | Chen, Christopher^{a; b; 1} | Ikram, Mohammad Kamran^{a; b; f; g; 1; *}

Affiliations: [a] Memory Ageing and Cognition Centre (MACC), National University Health System, Singapore | [b] Department of Pharmacology, National University of Singapore, Singapore | [c] Raffles Neuroscience Centre, Raffles Hospital, Singapore | [d] Departments of Radiology & Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands | [e] Faculty of Applied Sciences, Delft University of Technology, The Netherlands | [f] Singapore Eye Research Institute, Singapore National Eye Center, Singapore | [g] Academic Medicine Research Institute, Duke-NUS Graduate Medical School, Singapore

Correspondence: [*] Correspondence to: Mohammad Kamran Ikram, MD, PhD, The Academia, 20 College Road, Discovery Tower Level 6, Room 119, 169856 Singapore. Tel.: +65 6576 7234; kamran.ikram@duke-nus.edu.sg

Note: [1] Joint senior authors.

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. Objectives: 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. Conclusion: 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.

Keywords: Cognitive impairment, magnetic resonance imaging, risk factors, subcortical atrophy

DOI: 10.3233/JAD-150473

Journal: Journal of Alzheimer's Disease, vol. 48, no. 3, pp. 813-823, 2015