Agitation, Depression, Apathy Predictors of Progression from MCI to Dementia

Caroline Cassels

July 23, 2010

July 23, 2010 (Honolulu, Hawaii) — Agitation, apathy, and depression significantly predict progression from mild cognitive impairment (MCI) to incident dementia, according to the latest findings from the Mayo Clinic Study on Aging.

Presented here at the Alzheimer's Association International Conference on Alzheimer's Disease 2010, the prospective study showed that individuals with MCI and depression had a 63% increased risk of developing dementia compared with their counterparts with MCI alone. Similarly, the investigators found that the risk for dementia doubled for those with MCI and apathy compared with those with MCI without apathy. The risk is much higher (almost 3 times the increased risk) for persons with MCI and agitation.

"Our results suggest that neuropsychiatric symptoms may be very important clinical markers in predicting the progression from MCI to incident dementia. Additionally, this clinical marker is much cheaper than biomarkers," lead investigator Yonas E. Geda, MD, associate professor of neurology and psychiatry at the Mayo Clinic College of Medicine, Rochester, Minnesota, told Medscape Medical News.

Dr. Yonas E. Geda

According to Dr. Geda, previous relatively smaller studies indicate that neuropsychiatric symptoms such as depression and apathy predict progression from MCI to dementia, prompting the investigators to look at this hypothesis in a population-based setting with a larger sample size.

"We wanted to address this hypothesis in a definitive way using a much larger sample," said Dr. Geda. The prospective study included 275 patients with MCI who were followed-up for a median of 2.8 years to the outcome of incident dementia, as defined by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria.

Neuropsychiatric symptoms were assessed using the 12-item Neuropsychiatric Inventory Questionnaire.

Three neuropsychiatric symptoms — agitation, depression, and apathy — were significantly associated with progression to dementia.

According to the study, among 71 MCI patients with depression, 28 (40%) developed incident dementia, whereas of 201 MCI patients without depression, 51 (25%) developed incident dementia.

Of 49 MCI patients with apathy, 21 (43%) developed incident dementia, whereas of 226 MCI patients without apathy, 58 (26%) developed incident dementia.

A time-to-event cohort analysis was conducted. Hazard ratios (HR) and 95% confidence intervals (CI) were used to estimate the risk of progressing from MCI to incident dementia as predicted by depression, apathy, or agitation.

After adjusting for age, sex, and education, the results revealed that the HR for incident dementia in subjects who had MCI with apathy was 2.08 (95% CI, 1.25 - 3.48; P = .005), and for MCI with depression the HR was 1.63 (95% CI, 1.02 - 2.60; P = .043). MCI with agitation had an HR of 2.67 (95% CI, 1.46 - 4.88; P = .001).

Dr. Geda said the investigators, who include copresenter Mayo Clinic medical student Richard G. Cockerill, BSc, were surprised that there was no association between anxiety and progression from MCI to dementia.

"These findings suggest that clinicians should not stop at the diagnosis of MCI, but they should also conduct a neuropsychiatric assessment using standard instruments and look for depression, apathy, and agitation. We need a future interventional study to determine if treatment of neuropsychiatric symptoms could delay the progression from MCI to incident dementia," said Dr. Geda.

A prediction model developed by investigators at Johns Hopkins University, Baltimore, Maryland, indicates that delaying dementia by just 1 year could reduce the prevalence of Alzheimer's disease by nearly 800,000 cases in 2050.

The study was supported by the National Institutes of Health, Robert H. and Clarice Smith and Abigail Van Buren Alzheimer's Disease Research Program, and the Harold Amos Medical Faculty Development Program.

Alzheimer's Association International Conference on Alzheimer's Disease 2010: Abstract 01-05-05. Presented July 11, 2010.


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