Brain tissue volumes in relation to cognitive function and risk of dementia
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).
References (55)
- et al.
Probabilistic segmentation of brain tissue in MR imaging
Neuroimage
(2005) Age-related myelin breakdown: a developmental model of cognitive decline and Alzheimer's disease
Neurobiol. Aging
(2004)- et al.
Alzheimer's disease
Lancet
(2006) - et al.
A new rapid landmark-based regional MRI segmentation method of the brain
J. Neurol. Sci.
(2002) - et al.
Reliable manual segmentation of the frontal, parietal, temporal, and occipital lobes on magnetic resonance images of healthy subjects.
Brain Res. Brain Res. Protoc.
(2005) - et al.
Early diagnosis of Alzheimer's disease: contribution of structural neuroimaging
Neuroimage
(2003) Mild cognitive impairment: prevalence, prognosis, aetiology, and treatment
Lancet Neurol.
(2003)- et al.
Measures of brain morphology and infarction in the framingham heart study: establishing what is normal
Neurobiol. Aging
(2005) - et al.
Mini-mental state. A practical method for grading the cognitive state of patients for the clinician
J. Psychiatr. Res.
(1975) - et al.
Imaging of onset and progression of Alzheimer's disease with voxel-compression mapping of serial magnetic resonance images
Lancet
(2001)
Identifying severely atrophic cortical subregions in Alzheimer's disease
Neurobiol. Aging
Brain tissue volumes in the general elderly population. The Rotterdam Scan Study
Neurobiol. Aging
Cerebral changes on MRI and cognitive function: the CASCADE study
Neurobiol. Aging
Subjective memory complaints, education, and risk of Alzheimer's disease
Alzheimer's Dementia
Multi-spectral brain tissue segmentation using automatically trained k-nearest-neighbor classification
Neuroimage
Structural correlates of mild cognitive impairment
Neurobiol. Aging
Age-related sex differences in verbal memory
J. Clin. Psychol.
The histological validation of post mortem magnetic resonance imaging-determined hippocampal volume in Alzheimer's disease
Neuroscience
Staging of Alzheimer-related cortical destruction
Eur. Neurol.
Cognitive correlates of ventricular enlargement and cerebral white matter lesions on magnetic resonance imaging. The Rotterdam Study
Stroke
The hippocampus in aging and Alzheimer's disease
Neuroimag. Clin. N. Am.
White matter integrity and cognition in childhood and old age
Neurology
The biochemical pathway of neurofibrillary degeneration in aging and Alzheimer's disease
Neurology
Use of hippocampal and amygdalar volumes on magnetic resonance imaging to predict dementia in cognitively intact elderly people
Arch. Gen. Psychiatry
Brain volume loss in MCI predicts dementia
Neurology
White matter lesions in an unselected cohort of the elderly: molecular pathology suggests origin from chronic hypoperfusion injury
Stroke
Normative estimates of cross-sectional and longitudinal brain volume decline in aging and AD
Neurology
Cited by (107)
Visit-to-visit HbA1c variability, dementia, and hippocampal atrophy among adults without diabetes
2023, Experimental GerontologyThe association of diffusion tensor MRI measures of normal appearing white matter and cognition
2023, Cerebral Circulation - Cognition and BehaviorVascular Dementia and Cognitive Impairment
2021, Stroke: Pathophysiology, Diagnosis, and ManagementWhite matter hyperintensities and risks of cognitive impairment and dementia: A systematic review and meta-analysis of 36 prospective studies
2021, Neuroscience and Biobehavioral Reviews