Pauline Anderson

April 24, 2014

Mild cognitive impairment (MCI), both amnestic (aMCI) and nonamnestic (naMCI), is associated with increased mortality, but this association is stronger in patients with cognitive decline not affecting memory, a new study suggests.

There are 2 key reasons why tracking mortality risks among MCI subgroups is important, said lead researcher, Maria Vassilaki, MD, PhD, research fellow, Mayo School of Graduate Medical Education, Department of Neurology, Mayo Clinic, Rochester, Minnesota.

"The first is to understand the public health impact of having MCI, and the urgency of the need to prevent death in persons who develop MCI," she told Medscape Medical News. "Second, MCI is a heterogeneous condition, which means that there are different forms of the condition, with different underlying causes. These different causes, in turn, lead to different future outcomes. In this context, we think that mortality should also be investigated in each MCI type."

Failing to investigate mortality rates indifferent of MCI types may mean that researchers "may miss the opportunity to study and understand factors that lead to death in individuals with MCI, and the opportunity to implement interventions to reduce mortality in the different types of MCI," added Dr. Vassilaki.

The study results will be presented at the upcoming American Academy of Neurology (AAN) 66th Annual Meeting in Philadelphia, Pennsylvania, April 26 to May 3.

Determining MCI

The study used data from the Mayo Clinic Study of Aging (MCSA), an age- and sex-stratified random sample of residents of Olmsted County, Minnesota, aged 70 to 89 years. Participants underwent a neurologic evaluation and neuropsychological testing and were followed at 15-month intervals.

Dr. Maria Vassilaki

Participants were determined to have MCI if there was a cognitive concern, decline, or impairment; objective evidence of impairment in at least 1 cognitive domain (memory, executive function/attention, language, or visuospatial skills) based on multiple testing; essentially normal functional activities; and no dementia. Amnestic MCI was characterized by the presence of memory impairment.

Researchers determined deaths from Mayo Clinic databases and used proportional hazard models to estimate mortality rates for MCI cases vs cognitively normal participants.

During a median follow-up of 5.8 years, 331 of the 862 MCI cases and 224 of 1292 cognitively normal participants died. Compared with cognitively normal individuals, mortality was elevated in those with MCI (hazard ratio [HR], 1.81; 95% confidence interval [CI], 1.45 - 2.25) after adjustments for age, sex, years of education, APOE ε4 carrier status, history of stroke, heart disease, gait speed, diabetes, depression, and apathy.

However, the risk was higher for naMCI (HR, 2.26; 95% CI, 1.66 - 3.09) than for aMCI (HR, 1.68; 95% CI, 1.33 - 2.12).

The study also found that mortality was similar in those with MCI who later developed dementia (HR, 1.47) and those who did not develop dementia (HR, 1.48). Mortality was increased for both single-domain (HR, 1.76) and multiple-domain (HR, 1.49) aMCI and for single-domain (HR, 2.31) and multiple-domain (HR, 2.04) naMCI.

Causes of Death?

One of the next research steps will be to compare causes of death in the different MCI subgroups and in those without MCI to see whether this sheds some light on the varying mortality rates, said Dr. Vassilaki.

"It's possible that differences in etiology of the MCI types and differences in patterns of progression may contribute to the differences in mortality," she said. "In addition, other comorbidities, for example, concurrent diseases, related or unrelated to MCI, in the elderly could account for the differences in mortality."

Determining why patients with naMCI have a relatively higher mortality rate, "is something we need to study," said Dr. Vassilaki. "We need to generate new hypotheses for such increased mortality rates."

In addition, the researchers are continuing to monitor the MCSA participants. "It will be important to see whether such differences in death rates persist for longer follow-up periods," said Dr. Vassilaki.

The study was supported by an Alzheimer's Disease Patient Registry Grant.

American Academy of Neurology (AAN) 66th Annual Meeting. April 26-May 3, 2014. Abstract #P4.343.

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