Cognitive impairment in depression is not associated with neuropathologic evidence of increased vascular or Alzheimer-type pathology

Background: Cognitive impairment is common in depression, but underlying mechanisms remain unknown. We examined whether increases in Alzheimer-type or vascular pathology are associated with cognitive impairments in elderly depressed subjects. Methods: Eleven subjects who had died during a well-documented episode of DSM-IV major depression were included Neuropathologic assessments, blind to group membership, included standardized assessment of neuritic plaques, neurofibrillary tangles, and Lewy Bodies in frontal, temporal, parietal, and occipital cortices. Braak staging of Alzheimer pathology was also performed Cerebral microvascular disease was scored according to a previously validated scale, and a score for cerebral and systemic atheroma of large and medium sized arteries was obtained. Results: No subject had Lewy bodies. Plaque and tangle counts for all subjects were well within published norms for age-marched control subjects. There were no significant differences in plaque or tangle counts between subjects who were cognitively impaired (n = 5) and those who were nonimpaired (n = 6) during their depressive illness. Similarly, neither total microvascular pathology nor deep frontal microvascular pathology differed between the two groups. Conclusions: Our results indicate that the liability for some patients to develop cognitive impairment during a depressive episode is not related to an increase in Alzheimer-type or vascular neuropathologic change. This indicates that other mechanisms must underlie both the cognitive impairment associated with depression and the observation that depression is a risk factor for dementia. (C) 2001 Society of Biological Psychiatry.