Kate Johnson

June 11, 2014

ST. LOUIS — The combination of "late life" depression and increased cerebral beta-amyloid deposits in patients with mild cognitive impairment is a risk factor for quick progression to Alzheimer's disease, according to a longitudinal analysis from the Alzheimer's Disease Neuroimaging Initiative database.

Depression is likely a symptom rather than a cause of cognitive decline, according to researcher Matthias Brendel, PhD, from the Department of Nuclear Medicine at the University of Munich.

"Amyloid deposition occurs 20 years before the symptoms of Alzheimer's disease, so we think the mechanism could be that inflammation due to the deposition of the amyloid could cause depression," he said.

Dr. Brendel presented the results here at the Society of Nuclear Medicine and Molecular Imaging 2014 Annual Meeting.

The 371 study participants with mild cognitive impairment underwent cerebral beta-amyloid measurements with AV-45 PET, FDG PET, and T1-weighted MRI, and were followed for a mean of 22 months.

An imaging-based threshold of beta-amyloid deposition — a maximum standardized uptake value ratio (SUVrmax) of 1.10 — was used to categorize patients as positive (n = 206) or negative (n = 165) for beta-amyloid deposits.

Patients in the positive group were about 73 years of age, and those in the negative group were around 70.

The depression item on the Neuropsychiatric Inventory Questionnaire-Depression (NPI-Q) was used to assess depression and symptom severity.

Depressive symptoms were more prevalent in the positive than in the negative group (32% vs 25%).

In patients with more severe depression, amyloid deposits tended to be in the frontal cortex, Dr. Brendel told Medscape Medical News. In patients with little or no depression, amyloid deposits tended to be in the parietal temporal regions.

Progression to Alzheimer's Disease

Conversion from mild cognitive impairment to Alzheimer's disease was much more common in the positive group than in the negative group (21% vs 4%). However, in the cohort that progressed to Alzheimer's disease, depressive symptoms were less common in the positive group than in the negative group (45% vs 65%).

Progression from mild cognitive impairment to Alzheimer's disease was significantly faster in those with depressive symptoms (P < .01) and in those in the positive group (P < .001).

For patients strongly positive for beta-amyloid deposits (SUVrmax > 1.7) who were evaluable at 26-month follow-up, those with depressive symptoms were much more likely to convert to Alzheimer's disease than those without depressive symptoms (100% vs 45%; P < .005).

"Patients with high amyloid accumulation and coexistent depressive symptoms demonstrate a faster conversion from mild cognitive impairment to Alzheimer's disease, indicating a high-risk group," explained Dr. Brendel.

These findings could have implications for the selection of patients for treatment. Experimental amyloid-lowering approaches aimed at reducing cognitive decline would likely be wasted on amyloid-negative patients, he pointed out.

"There are many comorbidities in Alzheimer's disease, some of which can have synergic effects on the progression of Alzheimer's disease," said Satoshi Minoshima, MD, PhD, director of the neuroimaging and biotechnology laboratory at the University of Washington in Seattle.

Although more research is needed to confirm these findings, "if neurochemical changes underlying depression are found to be one of these, it could provide new insights into the pathophysiology of the disease and therapeutic benefits," said Dr. Minoshima.

Dr. Brendel and Dr. Minoshima have disclosed no relevant financial relationships.

Society of Nuclear Medicine and Molecular Imaging (SNMMI) 2014 Annual Meeting: Abstract 87. Presented June 8, 2014.


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