Depressive symptoms, clinical AD, and cortical plaques and tangles in older persons

Depressive symptoms in old age have been associated with risk of Alzheimer disease (AD), but it is uncertain whether they are an independent risk factor for disease or an early clinical sign of its underlying pathology. A group of 130 older Catholic nuns, priests, and brothers underwent detailed annual clinical evaluations and brain autopsy at death. The evaluations included administration of a modified 10-item Center for Epidemiologic Studies Depression Scale (CES-D) and 19 cognitive performance tests and clinical classification of dementia and AD. On postmortem examination, neuritic plaques, diffuse plaques, and neurofibrillary tangles in tissue samples from four cortical regions were counted, and a previously established composite measure of cortical plaque and tangle density (range 0 to 2.98) was derived. All analyses were adjusted for age, sex, and education. Participants reported a mean 1.5 depressive symptoms (SD 1.6) on the CES-D scale averaged across evaluations. In a logistic regression model, the odds of clinically diagnosed AD proximate to death increased by 1.33 (95% CI 1.01 to 1.76) for each depressive symptom and by 8.41 (95% CI 3.49 to 20.26) for each unit on the composite measure of pathology. In subsequent analyses, depressive symptoms were not related to level of pathology and did not modify the relation of pathology to clinical AD. In a series of linear regression models that controlled for pathology, depressive symptoms were related to level of cognitive function proximate to death and did not modify the association of pathology with cognition. The association of depressive symptoms with clinical AD and cognitive impairment appears to be independent of cortical plaques and tangles.