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The cerebellum in aging: cognitive function

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Titel The cerebellum in aging: cognitive function
Looptijd 01 / 2006 - 01 / 2010
Status Afgesloten
Onderzoeknummer OND1318047
Leverancier gegevens ZONMW

Samenvatting (EN)

Disturbances in motor and cognitive function are among the most important health problems in the elderly. It is well established that the cerebellum is critically involved in motor performance and plasticity, and more recently various clinical studies also point towards a role of the cerebellum in cognitive functions. However, up to now, the cerebellar role in the age-related decline in motor and cognitive functions has hardly been investigated. In two closely related projects, in which we will take advantage of the existing infrastructure and cohort of the ongoing Rotterdam Study, we propose to investigate these two putative roles of the cerebellum in age related disturbances. The Departments of Neuroscience, Radiology and Neuroepidemiology of the Erasmus MC have formed a consortium so that this long-term objective can be treated in a multidisciplinary fashion. In the present project (nr 2) we will focus on the role of the cerebellum in age-related disturbances of cognitive functioning (project 1 focuses on motor functioning). We will address the following specific aims: 1) What is the distribution of cerebellar atrophy in the general population and how does cerebellar atrophy relate to other degenerative brain changes; 2) Is cerebellar atrophy related to cognitive function and is this independent from other brain changes that may impair cognitive function?; and 3) are the known risk factors for cognitive decline and dementia associated with cerebellar atrophy? These questions will be investigated in the prospective, population based Rotterdam Study, in which all participants will undergo neuroimaging, repeated neuropsychological testing and are followed for incident dementia. This project should allow us to elucidate the role of the cerebellum in age-related decline of cognitive functioning. It is well established that the cerebellum plays a role in motor control and the ability to learn highly complex motor sequences. More recent studies suggest that the cerebellum is also involved in some higher cognitive functions (Schmahmann, 1998; Allen, 1997). Several case series report that adults with vascular or degenerative cerebellar disease show not only motor but also cognitive deficits (Gottwald, 2003). The human cerebellum changes with age. Total cerebellar volume declines with age, as do global cerebellar white matter volume, mean volume of the Purkinje cell body, and region specific volumes (Andersen, 2003). Volumetric MRI studies show significant volume loss in the cerebellum with age, especially in the vermis (Luft 1999; Raz 1998), although other regions may show atrophy as well (Oguro 1998) It is the long-term goal of our program to understand causes and consequences of cerebellar deficits due to aging. The cerebellum plays a role in motor control and the ability to learn highly complex motor sequences, as well as in some higher cognitive functions. We hypothesize that degenerative changes in the cerebellum play a role in the loss of motor and cognitive function that is often seen in elderly persons. The project will be carried out in two related aging projects, one focussing on the role of the cerebellum in motor function (project 1) and one on the role of the cerebellum in higher cognitive functions (project 2). The project described in this application (project 2) aims to investigate the role of cerebellar aging in the decline of cognitive function. The project will address the following specific aims: The number of elderly persons in today's societies is rapidly increasing. As a consequence, the impact of degenerative diseases is becoming more and more important. Among the most important health problems are disturbances in motor and cognitive function. Whereas major research efforts have focused on elucidating the role of neurodegenerative processes in cognitive function loss, relatively little has been done to unravel the causes of common age related motor problems. The motor problems that typically occur in aging include disturbances in gait, balance, and fine motor coordination. Similar symptoms can result from lesions of the cerebellum. This suggests an important role of the cerebellum in age related motor decline, yet this has never been investigated. Most research concerning age related neurodegenerative diseases until now focused on major clinical diseases particularly associated with pathological defects in higher brain regions; these include for example Alzheimer's disease, Parkinson's disease, and more recently Lewy Body disease. However, in a large proportion of elderly people changes in other brain areas occur as well, including changes in the cerebellum. Whether such cerebellar changes have a role in age related motor and cognitive decline is unclear. Further insight in the pathologic changes that underlie loss of motor and cognitive function may help the development and targeting of specific interventions. The Department of Neuroscience of the Erasmus MC has longstanding expertise in research on cerebellar learning and plasticity. This includes investigations at the genetic, molecular, cellular and systems neuro-anatomical level as well as at the neurophysiological and neuropsychological level. The Neuroepidemiology group of the Department of Epidemiology Study population The study will use the existing infrastructure and cohort of the ongoing Rotterdam Study. The Rotterdam Study is a prospective population-based study aimed at investigating determinants of chronic and disabling diseases in the elderly. The study started in 1990 when all inhabitants aged 55 years or over of Ommoord, a district of Rotterdam, were invited to participate. Of 10,275 eligible subjects 7,983 (78%) agreed to participate. At baseline, participants were interviewed at home and subsequently clinically examined during two visits at a research center. Baseline examinations included assessment of medical history, medication, non-invasive measurements of atherosclerosis, dietary assessments and measurements of vascular risk factors. Serum and DNA was collected and stored for future use. A first follow-up survey was done 1993-1994, and a second follow-up survey 1997-1999. The cohort was extended in 2000/2001 with 2988 persons who were then over the age of 55 years and lived in the study area. The third follow-up survey (for members in the cohort-extension the first follow-up survey) started in 2002. On January 1, 2003, 7019 participants were still alive and eligible. Mean age was 66.4 years (range 56-99) and 62% were women. In addition to the follow-up surveys, the total cohort is continuously being monitored for major morbidity and mortality, including onset of memory problems or dementia, through linkage of the GP records and the municipality records with the study database.

Betrokken organisaties

Penvoerder Afdeling Epidemiologie (EUR)
Financier ZonMw

Betrokken personen

Projectleider Prof.dr. M.M.B. Breteler
Projectleider Prof.dr. C.I. de Zeeuw

Classificatie

D23230 Neurologie, KNO , oogheelkunde
D23350 Psychiatrie, medische psychologie
D23363 Geriatrie

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