Neuropsychiatric Symptoms Implicated in Conversion From MCI to Dementia

Neuropsychiatric symptoms in the presence of mild cognitive impairment (MCI), including depression, appear to significantly increase the risk of conversion to dementia—either amnestic or Alzheimer’s type dementia—according to a report published February 20 in AJP in Advance.

Researchers at Johns Hopkins University School of Medicine and in the United Kingdom searched PubMed (from 1946) and Web of Knowledge (from 1900) through May 22, 2013 (updated June 5, 2014), using a variety of terms such as “mild cognitive,” “cognitive impairment,” and “age associated cognitive decline” included in longitudinal studies reporting potentially modifiable risk factors for incident dementia in people with MCI.

There were 76 eligible articles reporting epidemiologic and clinical studies.

A principal finding from the study was that diabetes, prediabetes, metabolic syndrome, and low serum folate levels increased risk of conversion from amnestic MCI to Alzheimer’s dementia and from any type or nonamnestic MCI to all-cause dementia.

But the researchers also found that the presence of neuropsychiatric symptoms predicted conversion to all-cause dementia. Among the findings are the following:

• There is evidence that more depressive symptoms predict conversion from any-type MCI to all-cause dementia from epidemiologic studies, but the evidence is inconsistent in clinical studies; it is also inconsistent as to whether depressive symptoms predict conversion from amnestic MCI to Alzheimer’s dementia or to any-cause dementia.

• There is evidence from clinical studies that the presence of neuropsychiatric symptoms in people with any-type MCI, but not their overall levels of symptoms, predicts conversion to all-cause dementia.

• There is inconsistent evidence about whether anxiety symptoms are associated with conversion from amnestic MCI to Alzheimer’s dementia and about whether apathy predicts the risk of conversion from amnestic MCI to Alzheimer’s dementia or from any-type MCI to dementia.

“A third to three-quarters of people with MCI have neuropsychiatric symptoms, most commonly depression, anxiety, apathy, and irritability,” the researchers stated. “Neuropsychiatric symptoms predicted conversion from any-type MCI to all-cause dementia. Neuropsychiatric symptoms may be etiologic for dementia, for example through neuroendocrine axis activation, or they may interact synergistically with a biological factor, such as genetic predisposition. Either of these putative relationships suggests that treating neuropsychiatric symptoms could theoretically delay dementia.”

Dilip Jeste, M.D.

Dilip Jeste, M.D., a past APA president and a professor of psychiatry and neurosciences and the Estelle and Edgar Levi Chair in Aging at the University of California, San Diego, said that the costs associated with dementia make identification of risk factors a valuable public-health task.

“This is an important paper based on a careful meta-analysis of 76 published articles reporting longitudinal studies on potentially modifiable risk factors for development of dementia in persons with mild cognitive impairment, or MCI,” he told Psychiatric News. “In DSM-5, dementia and MCI are labeled major and minor neurocognitive disorders, respectively. In general, between 35 percent and 45 percent of people with MCI develop dementia within three years. The total financial cost of dementia exceeds that of heart disease and cancer. Therefore, identifying and controlling risk factors for developing dementia among older adults with MCI is of clear public-health significance.

“These authors report that diabetes, pre-diabetes, metabolic syndrome, neuropsychiatric symptoms including depression, and lower serum folate levels were associated with variably increased risk of dementia, whereas the Mediterranean diet seemed to reduce the risk of developing dementia in patients with MCI,” Jeste added. “These findings suggest that control and prevention of diabetes, treatment of depressive and other neuropsychiatric symptoms, and use of a Mediterranean diet and of folate supplements may be helpful in lowering the risk of dementia in persons with MCI. A word of caution in interpreting the present results is that they are not based on large, randomized, controlled trials in individuals with MCI. Associations do not necessarily indicate causality or even directionality. Nonetheless, the recommendations should be helpful in at least some people and are consistent with good clinical practice.” ■