Cerebral changes on MRI and cognitive function: The CASCADE study
Introduction
Several forms of structural brain changes, such as white matter hyperintensities (WMHs) and atrophy, increase with age, and the impact of these brain changes on cognitive function has been explored in many studies [2], [10], [19]. However, most authors have considered only one or two measures at a time. Given that different types of WMHs and atrophy usually coexist, cognitive impairment may have been attributed to one of these, when it was actually due to another coexisting one. The aim of the present paper was to investigate a broader range of age-related brain changes in a European population-based sample, and determine their independent association to cognitive performance, given the impact of coexisting brain changes.
Cerebral white matter hyperintensities are commonly observed on the T2-weighted magnetic resonance imaging (MRI) scans of older people [4]. An issue still under investigation is whether WMHs affect cognitive performance, and if so, the extent to which they do. Several authors find a negative relation between the two, but there are also those who report a lack of association [2], [19]. Possible explanations for divergent findings have been discussed elsewhere [39]. Among the cognitive functions that seem to be affected by WMHs, speed and attention appear particularly impaired [3], [6], [45] although performance in other functions such as memory, frontal lobe and motor function also has been reported to be decreased [5], [6], [17], [21].
When the specific impact of subcortical versus periventricular WMHs has been examined, certain authors have found that subcortical WMHs particularly were associated with poor cognitive performance [5], whereas others have found the reverse [17], [45]. Earlier findings from the present study suggest that subcortical WMHs primarily affect speed, whereas periventricular hyperintensities are somewhat related to memory [39].
Cortical atrophy is a common feature of dementia [29], though it also occurs in normal aging [10], [41], albeit to a lesser extent [29], [41]. The relation between cortical atrophy and cognitive function has been frequently investigated and confirmed in, for example, semantic dementia [31] as well as Alzheimer's disease [29], [33]. Studies on non-demented individuals have yielded somewhat mixed findings. A strong connection has been found between atrophy and cognitive decline in individuals with Alzheimer's disease, but not in controls [29], [41]. However, cortical atrophy was associated with poorer cognitive function in several studies assessing perceptual and motor speeds, motor function, executive function, memory, and global cognitive function [10], [12], [26], [36].
A third common feature of normal aging is subcortical atrophy [11] also referred to as ventricular enlargement. In a non-demented population, ventricular enlargement was associated with poor performance in several cognitive tasks (global cognitive function, delayed memory and executive function), after controlling for age and sex [7]. Similar results have been obtained in other studies [12], [26]; but see [28].
As several types of cerebral changes usually co-exist in aging, it is difficult to assess the specific contribution of a given change to impairment in a given cognitive task. The aim of the present study was therefore to include several cerebral changes occurring in aging (subcortical and periventricular WMHs, and cortical and subcortical atrophy) and to examine their impact on a range of cognitive functions (episodic memory, word fluency, attention, and cognitive, perceptual, and motor speed) in cognitively intact individuals, given the impact of coexisting cerebral changes.
This study is a part of the Cardiovascular Determinants of Dementia project (CASCADE), a European multi-center project. CASCADE was designed to explore long- and short-term cardiovascular risk factors for white matter disease, such as lesions and atrophy, as well as cognitive consequences of such disease. The design of the project has been described elsewhere [23].
Section snippets
Methods
CASCADE includes 10 population-based cohorts in nine European countries: the Austrian Stroke Prevention Study, Austria; the EVA Study, France; the MEMO Study, Germany; the MATISS Study, Italy; the Zoetermeer Study, The Netherlands; the Rotterdam Scan Study, The Netherlands; Pol-CASCADE, Poland; MONICA-Catalonia, Spain; the BETULA Study, Sweden; the Whitehall II Study, United Kingdom. The whole sample consists of 1805 participants between 63 and 76 years of age (95% are between 65 and 75 years
Results
The distribution of brain changes varied somewhat between study centers, as did performance in the cognitive tests. The distribution of brain changes in the different study centers is portrayed in Table 2, and detailed data on cognitive performance in the centers are presented elsewhere [32].
Results from the hierarchical regression analyses are summarized in Table 3. For six of the 10 cognitive test measures (FLU, PPR, PPL, PPB, STT and STE), some type of cerebral change was associated with
Discussion
In this paper, data from eight European cohorts were pooled to investigate the impact of cerebral WMHs and atrophy on a number of cognitive tests in individuals with MMSE scores above 23. Hierarchical regression analysis controlling for age, education, sex, and study center showed that distinct types of cerebral changes predicted impaired performance in specific cognitive tests.
To our knowledge there are no previous studies with the present design, and the results should therefore be considered
Acknowledgements
Core funding for the collaborative work is provided by the European Union Directorate General XII. Siemens BV, The Netherlands is gratefully acknowledged for making possible the use of a mobile MRI machine. Imation International BV provided assistance for the MRI film. We thank B. Schra and D. Kraus (Daniel den Hoed Klinik, Rotterdam, The Netherlands) for their technical help in making and printing the MRI scans. We thank Dr. R. Motyl (Department of Neurology, University Hospital, Jagiellonian
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Formerly with Department of Epidemiology and Public Health, University College, London, UK.