University of Oulu

Cajanus A, Solje E, Koikkalainen J, Lötjönen J, Suhonen N-M, Hallikainen I, Vanninen R, Hartikainen P, de Marco M, Venneri A, Soininen H, Remes AM and Hall A (2019) The Association Between Distinct Frontal Brain Volumes and Behavioral Symptoms in Mild Cognitive Impairment, Alzheimer’s Disease, and Frontotemporal Dementia. Front. Neurol. 10:1059. doi: 10.3389/fneur.2019.01059

The association between distinct frontal brain volumes and behavioral symptoms in mild cognitive impairment, Alzheimer’s disease, and frontotemporal dementia

Saved in:
Author: Cajanus, Antti1,2; Solje, Eino1,2; Koikkalainen, Juha3;
Organizations: 1Institute of Clinical Medicine, Neurology, University of Eastern Finland, Kuopio, Finland
2Neurocenter, Neurology, Kuopio University Hospital, Kuopio, Finland
3Combinostics Ltd., Tampere, Finland
4MRC Oulu, Oulu University Hospital, Oulu, Finland
5Department of Radiology, Kuopio University Hospital, Kuopio, Finland
6Department of Neuroscience, University of Sheffield, Sheffield, United Kingdom
7Unit of Clinical Neuroscience, Neurology, University of Oulu, Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.7 MB)
Persistent link:
Language: English
Published: Frontiers Media, 2019
Publish Date: 2020-03-13


Our aim was to investigate the association between behavioral symptoms of agitation, disinhibition, irritability, elation, and aberrant motor behavior to frontal brain volumes in a cohort with various neurodegenerative diseases. A total of 121 patients with mild cognitive impairment (MCI, n = 58), Alzheimer’s disease (AD, n = 45) and behavioral variant frontotemporal dementia (bvFTD, n = 18) were evaluated with a Neuropsychiatric Inventory (NPI). A T1-weighted MRI scan was acquired for each participant and quantified with a multi-atlas segmentation method. The volumetric MRI measures of the frontal lobes were associated with neuropsychiatric symptom scores with a linear model. In the regression model, we included CDR score and TMT B time as covariates to account for cognitive and executive functions. The brain volumes were corrected for age, gender and head size. The total behavioral symptom score of the five symptoms of interest was negatively associated with the volume of the subcallosal area (β = −0.32, p = 0.002). High disinhibition scores were associated with reduced volume in the gyrus rectus (β = −0.30, p = 0.002), medial frontal cortex (β = −0.30, p = 0.002), superior frontal gyrus (β = −0.28, p = 0.003), inferior frontal gyrus (β = −0.28, p = 0.005) and subcallosal area (β = −0.28, p = 0.005). Elation scores were associated with reduced volumes of the medial orbital gyrus (β = −0.30, p = 0.002) and inferior frontal gyrus (β = −0.28, p = 0.004). Aberrant motor behavior was associated with atrophy of frontal pole (β = −0.29, p = 0.005) and the subcallosal area (β = −0.39, p < 0.001). No significant associations with frontal brain volumes were found for agitation and irritability. We conclude that the subcallosal area may be common neuroanatomical area for behavioral symptoms in neurodegenerative diseases, and it appears to be independent of disease etiology.

see all

Series: Frontiers in neurology
ISSN: 1664-2295
ISSN-E: 1664-2295
ISSN-L: 1664-2295
Volume: 10
Article number: 1059
DOI: 10.3389/fneur.2019.01059
Type of Publication: A1 Journal article – refereed
Field of Science: 3124 Neurology and psychiatry
Funding: This study was partly funded by the European Union 7th Framework Program for research, technological development, and demonstration VPH-DARE@IT (Grant Agreement No: 601055). In addition, this study was supported by grants from Finnish Medical Foundation, Olvi Foundation, Päivikki and Sakari Sohlberg foundation, Finnish Alzheimer's research association, Maire Taponen Foundation and Finnish Cultural Foundation. This is a summary of independent research partially carried out at the NIHR Sheffield Biomedical Research Centre (Translational Neuroscience). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. The support of the NIHR Clinical Research Facility – Sheffield Teaching Hospital was also acknowledged. This study was supported by the Academy of Finland (grant no. 315460).
Academy of Finland Grant Number: 315460
Detailed Information: 315460 (Academy of Finland Funding decision)
Copyright information: © 2019 Cajanus, Solje, Koikkalainen, Lötjönen, Suhonen, Hallikainen, Vanninen, Hartikainen, de Marco, Venneri, Soininen, Remes and Hall. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.