Psychiatric Symptoms May Precede Cognitive Decline

Laird Harrison

April 08, 2014

Elders with nonpsychotic psychiatric symptoms run an increased risk for mild cognitive impairment (MCI), a new study shows.

Agitation, apathy, anxiety, irritability, and depression all independently correlated to cognitive impairment, whereas delusion and hallucination did not, the researchers found.

"These baseline psychiatric symptoms were of similar or greater magnitude as biomarkers (genetic and structural MRI) in increasing the risk of incident mild cognitive impairment," the researchers, led by Yonas E. Geda, MD, Mayo Clinic in Scottsdale, Arizona, write.

The study was published online April 4 in the American Journal of Psychiatry.

Key Psychiatric Symptoms

Individuals with MCI develop dementia at a rate of 10% to 15% per year, compared with 1% to 2% per year in the general population.

Researchers are trying to determine who is at greatest risk so that they can develop targeted interventions.

To see whether neuropsychiatric status correlates to MCI, investigators evaluated 1408 people with a median age of 79.3 years in Olmsted County, Minnesota.

Participants underwent a neurologic evaluation by a physician, a risk factor assessment by a nurse or study coordinator, and a neuropsychological test interpreted by a neuropsychologist.

After adjusting for age, sex, education, and medical comorbidity, the researchers found that several psychiatric symptoms were associated with a much greater risk for cognitive decline. The correlation was statistically significant for agitation, apathy, anxiety, irritability, and depression (P < .0001).

Table. Psychiatric Symptoms Predicting Mild Cognitive Impairment

  Agitation Apathy Anxiety Irritability Depression
Hazard ratio 3.06 2.26 1.87 1.84 1.63


Although nighttime behavior also correlated with MCI, there were missing data, so the investigators recommended interpreting the results with caution.

Likewise, though euphoria and disinhibition were significant predictors, the analysis was based on a relatively small number of events.

Noncognitive Indicator of Neurodegeneration?

The researchers conducted secondary analyses to differentiate predicted amnestic or nonamnestic impairment. They found that euphoria, disinhibition, and nighttime behavior predicted nonamnestic impairment, but not amnestic impairment.

On the other hand, depression predicted amnestic impairment, but not nonamnestic impairment, whereas apathy predicted both.

The strength of the psychiatric symptoms was similar to the strength of such factors as hippocampal volume, the investigators reported.

It was also similar to the strength of apolipoprotein ε4, comorbid medical conditions, or demographic variables, such as education, as predictors.

The researchers speculated that psychiatric symptoms could be a noncognitive manifestation of the underlying neurodegenerative disorder that causes the cognitive impairment.

Alternatively, another neuropathology could cause both the cognitive and the psychiatric symptoms, they write. Or there could be some synergistic interaction between psychiatric symptoms and a biological factor, such as the apolipoprotein ε4 genotype.

The study was funded by the National Institutes of Health, the Mayo Clinic, the Robert Wood Johnson Foundation, the Robert H. and Clarice Smith and Abigail Van Buren Alzheimer's Disease Research Program, the European Regional Development Fund, and the Czech Ministry of Health. The researchers reported financial relationships to Allon Pharmaceuticals, Cephalon, GE Healthcare, Genentech, Janssen Alzheimer Immunotherapy, Merck, Pfizer, Roche, and various foundations.

Am J Psychiatry. Published online April 4, 2014. Abstract


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