Subjective Cognitive Impairment Early Indicator of Further Cognitive Deficits

Pauline Anderson

January 14, 2010

January 14, 2010 — A new study provides further evidence that dementia is a continuum that starts with subjective cognitive impairment (SCI) and moves to mild cognitive impairment (MCI), culminating in full-blown dementia.

SCI is characterized by subjective decline in memory and functioning but does not meet the clinical definition of MCI, in which subtle changes may become visible to observers and cognitive impairment is elicited with testing.

The study found that healthy subjects with SCI who were otherwise cognitively normal were 4.5 times more likely to develop MCI or dementia within about 7 years than healthy subjects without SCI.

The results demonstrate that SCI occurs on a continuum that eventually results in MCI and ultimately Alzheimer's disease (AD), said the study's lead author Barry Reisberg, MD, professor of psychiatry, director of the Fisher Alzheimer's Disease Program, and director, clinical core, at the New York University (NYU) Alzheimer’s Disease Center, NYU Langone Medical Center, New York City.

"The hypothesis was that it was a continuum, but this had to be proven," said Dr. Reisberg.

The research appears in the January issue of Alzheimer’s & Dementia.

"Eminently Normal"

The study included 213 community-dwelling subjects 40 years and older. A baseline assessment showed that 47 of these subjects had no cognitive impairment (NCI) and 166 had SCI. There was no difference between the NCI and SCI groups in sex or education, but there were significant differences in age (mean age, 64.1 and 67.5 years, respectively) and Mini-Mental State Examination (MMSE) scores (mean scores, 29.6 and 29.0, respectively).

"There wasn't a difference on psychometric test measures at baseline between persons with and without SCI; however, there was a significant difference on 1 objective test measure and that was the MMSE score," said Dr. Reisberg. He added that the mean score of 29 for SCI subjects on the MMSE was still "eminently normal."

The subjects were assessed about every 2 years for a mean of 6.8 years. During the study, researchers observed decline in 97 of the 213 subjects (45.5%). More SCI subjects (90 of 166 or 54.2%) declined compared with NCI subjects (7 of 47 or 14.9%).

Of the 7 NCI subjects who declined, 5 progressed to MCI (71.4%) and 2 to probable AD. Of the 90 SCI subjects who declined, 71 progressed to MCI (78.9%) and 10 to dementia. Controlling for baseline demographic variables and follow-up time, the hazard ratio for increased decline in SCI patients compared with NCI patients was 4.5.

The SCI subjects also declined more rapidly, taking on average 60% less time to decline than NCI subjects. The mean time to decline was 3.5 years longer for NCI than for SCI subjects.

Exciting Possibility of Prevention

These results suggest that AD might manifest many years before symptoms of dementia or even MCI are apparent and "raise the exciting possibility of conducting preventative studies" as early as 2 decades before the appearance of overt dementia, said the study authors.

Dr. Reisberg, who was involved in the development of the first medication to treat the symptoms of severe AD, said he would like to participate in research to develop the first medications for the prevention of MCI and dementia in the SCI stage.

Brain metabolism may be an area for future drug development research, said Dr. Reisberg. An earlier study at the NYU center showed an 18% decrement in metabolism in areas of the brain near the hippocampus in patients with SCI compared with non-SCI controls. "So measuring brain metabolism is 1 way to look for treatments," he said.

Some experts believe that certain lifestyle habits — for example, exercise and a healthy diet — may prevent progression from SCI to more serious cognitive deficits. However, according to Dr. Reisberg, conclusions about such interventions remain hypotheses. "There are no good double-blind, prospective prevention studies that have shown efficacy at this point."

According to the study authors, agents that might prove to be most useful in slowing the progression to MCI and AD in subjects with SCI are antioxidants, β- or γ-secretase inhibitors, and agents that reduce environmental exposure to toxins.

SCI affects 25% to 56% of the general population 65 years and older. The SCI stage could last 15 years before more serious cognitive problems develop, said Dr. Reisberg.

Dementia Continuum

Approached for a comment, William H. Thies, PhD, chief medical and scientific officer at the Alzheimer's Association in Chicago, Illinois, agreed that this research appears to confirm a dementia continuum and that it raises the issue of intervening at an earlier stage to prevent progression to overt symptoms of dementia.

"We will eventually be able to identify and treat people before they're symptomatic in order to prevent dementia from arising and even prevent these very early signs of cognitive decline," said Dr. Thies.

Future prevention strategies will be modeled after cholesterol management that reduce risks for heart disease, and such strategies will almost certainly include drugs, said Dr. Thies "People who have a mild tendency toward the disease may be able to prevent it with lifestyle changes, and as you have a stronger and stronger tendency toward the disease, you will need more and more help, and a part of that will be 1 or more medications."

There are currently 4 drugs prescribed to control symptoms associated with AD, but none of them stop the progression of the disease. "We need a drug that actually slows or stops progression," said Dr. Thies.

The study was supported in part by US Department of Health and Human Services; by grants from the National Institute on Aging, the National Institute of Mental Health of the US National Institutes of Health, and the US Department of Health and Human Services Administration on Aging; by a senior Clinical Research Fellowship provided by Forest Laboratories Inc; by a grant from the General Clinical Research Center Program of the National Center for Research Resources of the US National Institutes of Health; by the Fisher Center for Alzheimer’s Disease Research Foundation; and by grants from Mr. Zachary Fisher and Mrs. Elizabeth M. Fisher, Mr. William Silberstein, and Mr. Leonard Litwin. The authors have disclosed no relevant financial relationships.

Alzheimers Dement. 2010;6:11-24.


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