Depression, Sleeplessness, Irritability May Precede Dementia

Pauline Anderson

January 15, 2015

Irritability, depression, and nightime behavioral changes precede mental decline in cognitively normal patients who go on to develop dementia, a new study suggests.

On the basis of these results, physicians may want to investigate further if patients report these symtoms, said study author Catherine M. Roe, PhD, assistant professor, neurology, Washington University School of Medicine, St. Louis, Missouri.

"It sort of signals that if someone comes in complaining about feeling irritable and having a tough time sleeping, in addition to exploring different reasons for why they may be complaining of those symptoms, you may also consider asking about their thinking and memory because, according to this study, it seems those things are pretty common among people who are going to develop dementia," she told Medscape Medical News.

The study was published online January 14 in Neurology.

Dr Catherine M. Roe

Course of Symptoms

Researchers used the National Alzheimer's Coordinating Center Uniform Data Set, which is a repository of prospectively collected data from 34 Alzheimer's disease centers in the United States. Data of interest spanned from September 2005 to March 2013.

They investigated the time course of noncognitive symptoms reported on the 10-item Functional Activities Questionnairre (FAQ), which assesses difficulty in activities of daily living; the 15-item Geriatric Depression Scale (GDS); and the Neuropsychiatric Inventory Questionnaire (NPI-Q), which consists of 12 items, each assessing 12 neuropsychiatric symptom domains.

The analysis included 2416 participants who were cognitively normal at baseline and had no positive symptoms on the FAQ, GDS, or NPI-Q. Of these,1198 remained cognitively normal (Clinical Dementia Rating [CDR] of 0) over the course of the study and 1218 participants who progressed to a CDR of greater than 0. The two samples were similar in terms of APO status, age, education, and length of follow-up.

Almost all (97.2%) of those who developed incident cognitive impairment had very mild dementia (CDR, 0.5) while 2.1% were rated with a CDR of 1 (mild impairment), 0.7% with a CDR of 2 (moderate dementia), and 0.1% with a CDR of 3 (severe dementia).

Researchers compared the order of symptom development between participants who remained at a CDR of 0 and those who had a CDR greater than 0. They found that the order on the NPI-Q was similar in the two groups, although the time to each symptom other than elation or euphoria was faster for those who received a CDR greater than 0 compared with those who did not (P < .001).

The similar sequence of noncognitive symptoms on the NPI-Q trended into three phases: first, irritability, depression, and nightime behavioral changes; followed by anxiety, appetitie changes, agitation, and apathy; and last, elation, motor disturbances, hallucinations, delusions, and disinhibition.

Among the earliest symptoms was lack of energy, "which is not what you normally think of when you think of Alzheimer's disease," commented Dr Roe. While this still needs replication in other samples, physicians could start probing about memory problems in patients whose lack of energy isn't attributable to anemia or other causes, she said.

If impairment in activities of daily living, such as paying bills, shopping, and preparing meals, did appear, they tended to be among the symptoms showing up later in those who developed very mild cognitive impairment, noted Dr Roe.

With the exception of memory, the GDS symptoms reported by both groups were similar.

Solidifies Evidence

Commenting for Medscape Medical News, Glen Finney, MD, chief, Behavioural Neurology Division, University of Florida, Gainesville; president, Florida Society of Neurology; and member of the American Academy of Neurology, said the study "solidifies" what is known about depression and other behavioral symptoms. These, he said, precede cognitive symptoms "by months, even years" in patients who develop dementia.

"It makes it clear just how strong this connection is, and which types of behavioral changes are earlier and which are later."

The fact that patients have worsening behavioral symptoms before showing any evidence of cognitive or functional decline suggests that these symptoms "are part of an underlying neurologic decline rather than a psychological reaction," said Dr Finney.

He agreed that patients showing these behavioral symptoms "need to be much more closely followed cognitively so we can intervene earlier if there are subsequent changes, which can have real benefits in terms of quality of life."

The findings have important research implications, added Dr Finney. "We are always looking for these earliest markers of risk that we can then study to find what kinds of therapies or treatments or lifestyle modifications could bend the curve in their favor of not developing subsequent cognitive and functional decline."

The study was supported by the Longer Life Foundation, National Institute on Aging, Fred Simmons and Olga Mohan and the Washington University Knight Alzheimer's Disease Research Center. Dr Roe and Dr Finney have disclosed no relevant financial relationships.

Neurology. Published online January 14, 2015. Abstract

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