Elsevier

Neurobiology of Aging

Volume 31, Issue 3, March 2010, Pages 378-386
Neurobiology of Aging

Brain tissue volumes in relation to cognitive function and risk of dementia

https://doi.org/10.1016/j.neurobiolaging.2008.04.008Get rights and content

Abstract

We investigated in a population-based cohort study the association of global and lobar brain tissue volumes with specific cognitive domains and risk of dementia. Participants (n = 490; 60–90 years) were non-demented at baseline (1995–1996). From baseline brain MRI-scans we obtained global and lobar volumes of CSF, GM, normal WM, white matter lesions and hippocampus. We performed neuropsychological testing at baseline to assess information processing speed, executive function, memory function and global cognitive function. Participants were followed for incident dementia until January 1, 2005. Larger volumes of CSF and WML were associated with worse performance on all neuropsychological tests, and an increased risk of dementia. Smaller WM volume was related to poorer information processing speed and executive function. In contrast, smaller GM volume was associated with worse memory function and increased risk of dementia. When investigating lobar GM volumes, we found that hippocampal volume and temporal GM volume were most strongly associated with risk of dementia, even in persons without objective and subjective cognitive deficits at baseline, followed by frontal and parietal GM volumes.

Introduction

Several biomarkers for cognitive impairment and dementia have been identified using magnetic resonance imaging (MRI) of the brain. Medial temporal lobe atrophy, including hippocampal atrophy, is closely related to memory impairment and is a strong predictor of dementia even in asymptomatic persons (de Leon et al., 1995, den Heijer et al., 2006, Fox et al., 2001, Jack et al., 2002, Smith et al., 2007). Subcortical vascular disease, as reflected by white matter lesions (WML) and lacunar infarcts, is thought to contribute to the development of dementia by primarily affecting a different cognitive domain than memory, namely information processing speed (Prins et al., 2005, Swan et al., 2000).

Several studies have suggested that persons with whole-brain atrophy also have poorer global cognition and suffer more often from dementia than persons without atrophy (Erten-Lyons et al., 2006, Jack et al., 2005). However, little is known whether this applies evenly to atrophy of all brain regions and for all cognitive domains. Moreover, few studies distinguished between grey matter (GM) and white matter (WM) atrophy. Previous studies have used visual ratings of sulcal width as an indirect marker of GM atrophy, and ventricular enlargement as an indirect marker of WM atrophy, and found inconsistent results regarding their relationship with specific cognitive domains (Breteler et al., 1994, Longstreth et al., 2000, Mosley et al., 2005, Soderlund et al., 2006). Recent advances in the analysis of brain MRI-data have opened the way for automated in vivo volumetric quantification of the whole brain, and of GM and WM (DeCarli et al., 2005, Fotenos et al., 2005). The use of these direct volumetric measures of GM and WM atrophy may allow for a better assessment of specific effects on cognition.

Atrophy of the hippocampus, which is a predominantly GM structure, is thought to be one of the first detectable signs of dementia (de Leon et al., 1995). Post-mortem and neuroimaging studies in dementia patients have shown that atrophic changes in GM are present throughout the brain, and that these changes probably develop later in the course of the disease (Blennow et al., 2006, Braak et al., 1993, Delacourte et al., 1999, Halliday et al., 2003, Sonnen et al., 2007). Little is known about whether brain atrophy outside the hippocampus is discernible during the preclinical phase of dementia.

We investigated in a population-based cohort study the association of GM and WM volume with specific cognitive domains and with the risk of dementia. Furthermore, we investigated how atrophy of the different cerebral lobes was related to dementia, and whether lobar atrophy predicted dementia in asymptomatic persons.

Section snippets

Participants

This study is based on the Rotterdam Scan Study, a large population-based cohort study in the Netherlands, investigating age-related brain changes on MRI (Prins et al., 2005, Vermeer et al., 2003). At baseline (1995–1996), we randomly invited participants (60–90 years) stratified by sex and 5-year age strata from the Zoetermeer Study and the Rotterdam Study to participate in the Rotterdam Scan Study (Hofman et al., 2007, Prins et al., 2005). Individuals who were demented, blind or had an MRI

Results

Table 1 shows the baseline characteristics of the study population. Table 2 shows the cross-sectional association between global brain tissue volumes and cognitive performance. Larger volumes of CSF and WML were related to a lower MMSE score and all cognitive domains. Larger volumes of total WM and normal WM were related to better performance on the MMSE, higher information processing speed, and borderline with better executive function, whereas larger GM volume was significantly related to

Discussion

In this population-based cohort study we found that volumes of WM and GM relate differently to specific cognitive domains and to the risk of dementia. Atrophy of WM was related to worse MMSE scores, lower psychomotor speed and worse executive function, but not to risk of dementia. In contrast, GM atrophy was related to worse memory performance and to an increased risk of dementia. When analyzed at the lobar level, hippocampal and temporal GM atrophy were most strongly associated with dementia,

Conflict of interest

None of the authors has any actual or potential conflicts of interest related to this manuscript, including any financial, personal or other relationships with other people or organizations within three years of beginning the work submitted that could inappropriately influence (bias) their work.

Disclosure

None of the authors has anything to disclose in relation to this manuscript.

Acknowledgement

This study was financially supported by the Netherlands Organization for Scientific Research (NWO) (grant 918-46-615).

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