Disinhibition in dementia related to reduced morphometric similarity of cognitive control network

Author:

Jenkins Lisanne M1ORCID,Heywood Ashley1ORCID,Gupta Sonya1,Kouchakidivkolaei Maryam2,Sridhar Jaiashre3,Rogalski Emily13,Weintraub Sandra13ORCID,Popuri Karteek4,Rosen Howard5,Wang Lei6ORCID, ,Rosen Howard,Dickerson Bradford C,Domoto-Reilly Kimoko,Knopman David,Boeve Bradley F,Boxer Adam L,Kornak John,Miller Bruce L,Seeley William W,Gorno-Tempini Maria-Luisa,McGinnis Scott,Mandelli Maria Luisa

Affiliation:

1. Psychiatry and Behavioral Sciences, Northwestern University , Chicago, IL 60611 , USA

2. School of Engineering Science, Simon Fraser University , Burnaby, BC V5A 1S6 , Canada

3. Mesulam Center for Cognitive Neurology and Alzheimer’s Disease, Northwestern University , Chicago, IL 60611 , USA

4. Computer Science, Memorial University of Newfoundland , St. Johns, NL A1C 5S7 , Canada

5. Neurology, University of California , San Francisco, CA 94143 , USA

6. Psychiatry and Behavioral Health, Ohio State University , Columbus, OH 43210 , USA

Abstract

Abstract Disinhibition is one of the most distressing and difficult to treat neuropsychiatric symptoms of dementia. It involves socially inappropriate behaviours, such as hypersexual comments, inappropriate approaching of strangers and excessive jocularity. Disinhibition occurs in multiple dementia syndromes, including behavioural variant frontotemporal dementia, and dementia of the Alzheimer’s type. Morphometric similarity networks are a relatively new method for examining brain structure and can be used to calculate measures of network integrity on large scale brain networks and subnetworks such as the salience network and cognitive control network. In a cross-sectional study, we calculated morphometric similarity networks to determine whether disinhibition in behavioural variant frontotemporal dementia (n = 75) and dementia of the Alzheimer’s type (n = 111) was associated with reduced integrity of these networks independent of diagnosis. We found that presence of disinhibition, measured by the Neuropsychiatric Inventory Questionnaire, was associated with reduced global efficiency of the cognitive control network in both dementia of the Alzheimer’s type and behavioural variant frontotemporal dementia. Future research should replicate this transdiagnostic finding in other dementia diagnoses and imaging modalities, and investigate the potential for intervention at the level of the cognitive control network to target disinhibition.

Funder

National Institutes of Health

National Center for Advancing Translational Sciences

Alzheimer’s Disease Research Center

National Institute on Aging

Natural Sciences and Engineering Research Council of Canada

Publisher

Oxford University Press (OUP)

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