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Increased Neurofibrillary Tangles in Patients With Alzheimer Disease With Comorbid Depression

From the Department of Psychiatry (MAR, MS-B, DP Purohit, DP Perl, VH, MS), Mount Sinai School of Medicine, New York; the Department of Psychiatry (MAR), Charité Mitte, Humboldt University, Berlin, Germany; Bronx Veterans Affairs Hospital (DP Purohit, VH, MS), Bronx, NY; and the Department of Pathology (DP Perl), Mount Sinai School of Medicine, New York.

Objective: Recent evidence suggests that a history of major depression may lead to increases in hippocampal neuropathology in Alzheimer disease (AD). The authors tested the hypothesis that neuritic plaques and neurofibrillary tangles are more pronounced in the brains of patients with AD with comorbid depression as compared with patients with AD without depression.

Methods: Brain samples from patients were selected from the U.S. National Alzheimer's Coordinating Center database. The primary analysis included 7164 individuals: 6468 had AD as the primary neuropathologic diagnosis and 696 were considered neuropathologically normal. Depression at study inclusion was rated as present or absent in consensus conferences. Neuropathologic ratings from the Consortium to Establish a Registry in Alzheimer's Disease rating of neuritic plaques and Braak staging of neurofibrillary tangles were used for between-group analyses.

Results: Brains of patients with AD with comorbid depression showed higher levels of cortical tangle formation than brains of patients with AD without comorbid depression. Results remained stable when controlling for age, gender, level of education, and cognitive status. Within patients with AD, comorbid depression increased the odds for advanced neuropathologic disease stage (odds ratio: 1.47; 95% confidence interval: 1.03–2.08).

Conclusion: In AD, the presence of depression comorbidity corresponds to increases in AD-related neuropathologic changes beyond age, gender, level of education, and cognitive status, suggesting an interaction between depression and the neuropathologic processes in AD

Key Words: depression • Alzheimer disease • neuropathology