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Relationship of vascular risk to the progression of Alzheimer disease

From Royal Free & University College Medical School (C.R., Z.W., G.L.), UCL, Department of Mental Health Sciences, London; Kent Institute of Medicine and Health Sciences (C.K.), Canterbury; and Department Clinical Biochemistry (J.H., J.D.), Royal Brompton Hospital, London, UK.

Address correspondence and reprint requests to Dr. Ciaran Regan, Royal Free & University College Medical School, UCL, Department of Mental Health Sciences, Holborn Union Building, Archway Campus, Highgate Hill, London N19 5LW UK; e-mail: ciaran.regan{at}ucl.ac.uk

Objective: To test the hypothesis that patients with Alzheimer disease (AD) who have vascular risk factors have a worse prognosis over 18 months vs those without such risk factors.

Methods: A sample of 224 people with AD and their caregivers were recruited purposively to be representative of people with dementia in terms of cognition, sex, and living situations in a longitudinal study of AD. Standardized instruments measuring cognition, functional status, and neuropsychiatric symptoms were used to collect data. Physical examination and relevant blood tests were performed.

Result: There was no difference in rate of deterioration between people with and without vascular risk factors, except in those who had a cerebrovascular accident (CVA) during the 18-month follow-up (p < 0.001). We considered possible confounders of outcome: sex, age, years of education, severity of dementia, depression, taking cholinesterase inhibitors (AChEIs), and whether those with vascular risk factors were more likely to die, but the results remained unchanged. Stopping AChEIs during the study was associated with cognitive and functional decline (p < 0.001).

Conclusions: Vascular risk factors as measured clinically and biochemically do not significantly increase deterioration at 18 months in people with Alzheimer disease who have a low burden of cerebrovascular risk factors. However, cerebrovascular events are associated with more rapid decline. Vascular risk factors may contribute to the expression of Alzheimer disease initially but are not part of the underlying etiologic process.

Editorial, see page 1326

See also page 1363

Disclosure: Lundbeck SA funded the data collection but did not participate in preparation, review, or approval of the manuscript. C.K. and G.L. have received grants from Lundbeck SA in excess of $10,000.

Received February 24, 2006. Accepted in final form July 5, 2006.

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