November 9, 2011 — Amyloid plaques and tau tangles in the brains of older individuals may indicate not only Alzheimer's disease (AD) and other dementias but also major depression, a new imaging study suggests.
Using FDDNP, a novel chemical marker, investigators at the University of California, Los Angeles, showed that patients with late-life major depressive disorder (MDD) had a greater burden of amyloid beta (Aβ) plaques and tau tangles in critical brain regions including the posterior cingulate (PC) and lateral temporal areas.
"These findings suggest that the higher protein load in critical brain regions may contribute to the development of severe depression in late life," principal investigator Gary Small, MD, said in a release.
The study appears in the November issue of the Archives of General Psychiatry.
Precursor to Dementia
One of the most common mental disorders in the elderly population, MDD is responsible for significant adverse medical, psychosocial, and economic outcomes.
Although the biological underpinnings of major depression remain unclear, possible culprits include neurodegeneration and/or vascular mechanisms. Previous imaging studies show that compared with control patients, patients with MDD have smaller brain volumes, which is widely considered a marker of neurodegeneration.
The investigators note that vascular mechanisms are also relevant to the pathogenesis of MDD and state that neurodegeneration and vascular injury may work in tandem in the manifestation of the disorder.
Preliminary evidence from plasma data indicate that in addition to being an early biomarker of AD, the ratio of Aβ-42 to Aβ-40 may also be a biomarker for MDD.
Furthermore, depression in the elderly has been identified as a risk factor and a precursor for AD.
Higher Protein Load
Using FDDNP positron emission tomography (PET), the researchers examined and compared amyloid and tau protein binding in 20 patients with late-life MDD with that found in 19 healthy control patients matched for age, sex, and education level.
The study's primary outcome measure was the relative distribution volume of the proteins in regions of interest including the PC gyrus and mesial temporal, lateral temporal, frontal, and parietal lobes in all study participants.
Investigators found that patients with late-life MDD had significantly higher FDDNP binding globally, with a particular concentration found in the lateral temporal and PC regions compared with in the healthy counterparts. Other regions including the anterior cingulated and mesial temporal also showed higher FDDNP binding compared with control patients, but the difference did not reach significance.
"These findings suggest that neuronal injury associated with higher protein load in critical brain regions might provide a mechanism in the pathophysiologic manifestation of MDD in late life and have implications for the therapeutics of depression in elderly individuals," the authors write.
Larger, longitudinal studies are needed to determine whether higher FDDNP binding at baseline leads to AD over time. PET imaging with FDDNP before and after treatment with antidepressants and/or antiamyloid agents may provide useful information about whether such agents can change the course of amyloid deposition, and if so, whether this has a positive effect on clinical outcomes.
"We may find that depression in the elderly may be an initial manifestation of progressive neurodegenerative disease. Brain scans using FDDNP allow us to take a closer look at the different types of protein deposits and track them to see how clinical symptoms develop," Anand Kumar, MD, the study's first author, said in a statement.
The study was supported by the National Institutes of Health. The University of California, Los Angeles, owns 3 US patents on the FDDNP clinical marker. Dr. Small and author Jorge R. Barrio, PhD, are among the inventors of FDDNP. Full disclosures are listed in the original article.
Arch Gen Psych. 2011;68:1143-1150. Full text
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Cite this: Dementia Pathology Linked to Late-Life Major Depression - Medscape - Nov 09, 2011.
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