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Tom den Heijer, MD, PhD; Mirjam I. Geerlings, PhD; Freek E. Hoebeek, PhD; Albert Hofman, MD, PhD; Peter J. Koudstaal, MD, PhD; Monique M. B. Breteler, MD, PhD

Arch Gen Psychiatry. 2006;63:57-62.

Context  The recent focus on the development of preventive interventions for Alzheimer disease has fueled the search for biomarkers of presymptomatic disease. Patients with Alzheimer disease and mild cognitive impairment have marked atrophy of the hippocampus and amygdala compared with healthy elderly people. Whether atrophy of these structures is also present in persons without cognitive impairment who later develop dementia is unknown.

Objective  To assess whether volumetric assessment of the hippocampus and amygdala using magnetic resonance imaging (MRI) predicts dementia in elderly people without cognitive impairment.

Design  Longitudinal cohort study.

Setting  A general community in the Netherlands.

Participants  Five hundred eleven persons, aged 60 to 90 years, free of dementia at baseline were followed up during 3043 person-years (mean per person, 6.0 years). We performed volumetric assessment of the hippocampus and amygdala, obtained information about daily memory problems, and performed extensive neuropsychological testing in all study participants.

Main Outcome Measure  Dementia, as assessed by repeated neuropsychological screening and monitoring of medical records.

Results  Thirty-five persons developed dementia (26 with Alzheimer disease). Hippocampal and amygdalar volumes were strongly associated with the risk of dementia; the age-, sex-, and education-adjusted hazard ratio per 1-SD decrease in volume was 3.0 (95% confidence interval, 2.0-4.6) for the hippocampus and 2.1 (95% confidence interval, 1.5-2.9) for the amygdala. The hazard ratios associated with atrophy were similar in persons without memory complaints or low cognitive function at baseline. Compared with those remaining free of dementia, baseline brain volumes were 17% smaller in persons who received a clinical diagnosis of dementia within 2 to 3 years after MRI and still 5% smaller in those whose conditions were diagnosed 6 years after MRI.

Conclusion  Atrophy of the hippocampus and amygdala on MRI in cognitively intact elderly people predicts dementia during a 6-year follow-up.

Author Affiliations: Departments of Epidemiology and Biostatistics (Drs den Heijer, Geerlings, Hoebeek, Hofman, and Breteler) and Neurology (Drs den Heijer and Koudstaal), Erasmus Medical Center, Rotterdam, the Netherlands; and Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, the Netherlands (Dr Geerlings).

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