Increased Neurofibrillary Tangles in Patients With Alzheimer Disease With Comorbid Depression

doi:10.1097/JGP.0b013e31816029ec

The American Journal of Geriatric Psychiatry

Volume 16, Issue 2, February 2008, Pages 168-174

https://doi.org/10.1097/JGP.0b013e31816029ec Get rights and content

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

Section snippets

Participants

The study builds on the neuropathologic portion from the U.S. National Alzheimer's Coordinating Center (NACC) database. The NACC database (2005 data set) as of December 2005 consisted of demographic and clinical data on 8,534 patients with dementia and healthy comparison subjects enrolled at 32 AD centers in the United States funded through the National Institute on Aging. These subjects are a referral sample. Data were stored without personal identifiers, and each center obtained Institutional

Demographic and Clinical Characteristics

The overall study group (N = 7164) comprised 3,435 women (47.9%) and 3,729 men (52.1%) with a mean age at death of 79.20 years (SD [SD]: 10.48; range: 55–111 years), a mean education level of 13.99 years (SD: 3.64; range: 0–30 years), and a mean MMSE score at last assessment of 13.72 (SD: 9.19; range: 0–30). A total of 93.8% of the sample (N = 6,717) were white, 2.8% (N = 206) were black, and 1.4% (N = 103) were Hispanic with all other ethnicities accounting for less than 2% of the sample.

DISCUSSION

We found distinct differences in the assessment of tangles by Braak staging in brains of patients with AD as a function of comorbid depression. Specifically, we were able to show that patients with a neuropathologically confirmed diagnosis of AD who have comorbid depression were more likely to have advanced stages of neurofibrillary tangles than patients with AD without comorbid depression. The effect conveyed by depression comorbidity on neuropathologic changes was rather small. However,

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We thank Dr. Kukull and two anonymous reviewers from NACC for helpful comments on an earlier version of this manuscript. MAR is a Junior Fellow of MaxNetAging, the Aging Network of the Max Planck Society.

This study was supported in part by grant P01-AG02219 (VH) and by grants U01-AG016976 (Dr. Kukull) and P01-AG05138 (MS) from the National Institute on Aging and by a National Alzheimer's Coordinating Center (NACC) Junior Investigator Award (MAR).

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Regular Research ArticlesIncreased Neurofibrillary Tangles in Patients With Alzheimer Disease With Comorbid Depression

Objective

Methods

Results

Conclusion

Section snippets

Participants

Demographic and Clinical Characteristics

DISCUSSION

Am J Geriatr Psychiatry

J Biol Chem

Neurobiol Aging

Neurobiol Aging

Am J Geriatr Psychiatry

Am J Geriatr Psychiatry

Gen Hosp Psychiatry

Neurobiol Aging

Neurobiol Aging

Evolution of the neuropathology of Alzheimer's disease

Acta Neurol Scand

Beta-protein amyloid is widely distributed in the central nervous system of patients with Alzheimer's disease

Am J Pathol

The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). part II. Standardization of the neuropathologic assessment of Alzheimer's disease

Neurology

Pathology of Alzheimer's disease

Depression as a risk factor for Alzheimer disease: the MIRAGE Study

Arch Neurol

The temporal relationship between depressive symptoms and dementia: a community-based prospective study

Arch Gen Psychiatry

Psychiatric history and related exposures as risk factors for Alzheimer's disease: a collaborative re-analysis of case–control studies. EURODEM Risk Factors Research Group

Int J Epidemiol

Clinical risk factors for Alzheimer's disease: a population-based case–control study

Neurology

Interaction between genetic and environmental risk factors for Alzheimer's disease: a reanalysis of case–control studies. EURODEM Risk Factors Research Group

Genet Epidemiol

History of depression as a risk factor for Alzheimer's disease

Epidemiology

Regular Research Articles
Increased Neurofibrillary Tangles in Patients With Alzheimer Disease With Comorbid Depression