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Multiple Cognitive and Behavioral Factors Link Association Between Brain Structure and Functional Impairment of Daily Instrumental Activities in Older Adults

Published online by Cambridge University Press:  26 July 2021

Seyul Kwak
Department of Psychiatry, Seoul Metropolitan Government-Seoul National University College Boramae Medical Center, Seoul, Republic of Korea
Su Mi Park
Department of Psychiatry, Seoul Metropolitan Government-Seoul National University College Boramae Medical Center, Seoul, Republic of Korea Department of Counseling Psychology, Hannam University, Daejeon, Republic of Korea
Yeong-Ju Jeon
Department of Psychiatry, Seoul Metropolitan Government-Seoul National University College Boramae Medical Center, Seoul, Republic of Korea
Hyunwoong Ko
Department of Psychiatry, Seoul Metropolitan Government-Seoul National University College Boramae Medical Center, Seoul, Republic of Korea Interdisciplinary Program in Cognitive Science, Seoul National University, Seoul, Republic of Korea
Dae Jong Oh
Department of Psychiatry, Seoul Metropolitan Government-Seoul National University College Boramae Medical Center, Seoul, Republic of Korea
Jun-Young Lee*
Department of Psychiatry, Seoul Metropolitan Government-Seoul National University College Boramae Medical Center, Seoul, Republic of Korea
*Correspondence and reprint requests to: Jun-Young Lee, Department of Psychiatry, Seoul National University College of Medicine & SMG-SNU Boramae Medical Center, Seoul07061, Republic of Korea. Email:



Functional impairment in daily activity is a cornerstone in distinguishing the clinical progression of dementia. Multiple indicators based on neuroimaging and neuropsychological instruments are used to assess the levels of impairment and disease severity; however, it remains unclear how multivariate patterns of predictors uniquely predict the functional ability and how the relative importance of various predictors differs.


In this study, 881 older adults with subjective cognitive complaints, mild cognitive impairment (MCI), and dementia with Alzheimer’s type completed brain structural magnetic resonance imaging (MRI), neuropsychological assessment, and a survey of instrumental activities of daily living (IADL). We utilized the partial least square (PLS) method to identify latent components that are predictive of IADL.


The result showed distinct brain components (gray matter density of cerebellar, medial temporal, subcortical, limbic, and default network regions) and cognitive–behavioral components (general cognitive abilities, processing speed, and executive function, episodic memory, and neuropsychiatric symptoms) were predictive of IADL. Subsequent path analysis showed that the effect of brain structural components on IADL was largely mediated by cognitive and behavioral components. When comparing hierarchical regression models, the brain structural measures minimally added the explanatory power of cognitive and behavioral measures on IADL.


Our finding suggests that cerebellar structure and orbitofrontal cortex, alongside with medial temporal lobe, play an important role in the maintenance of functional status in older adults with or without dementia. Moreover, the significance of brain structural volume affects real-life functional activities via disruptions in multiple cognitive and behavioral functions.

Research Article
Copyright © INS. Published by Cambridge University Press, 2021

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