Alicia Ault

March 22, 2016

WASHINGTON ― Evidence is mounting that complaints of subjective memory loss, also known as subjective cognitive impairment (SCI), are indeed indicators of future cognitive impairment and should be addressed, Alzheimer's disease experts say.

In a session here at the American Association for Geriatric Psychiatry (AAGP) 2016 Annual Meeting, researchers presented and summarized the growing body of data showing that patients' memory complaints should not be taken lightly.

"This is an area people have just been ignoring, the so-called worried well, or people with subjective complaints," Barry Reisberg, MD, professor of psychiatry and director of the Zachary and Elizabeth M. Fisher Alzheimer's Research Foundation's Disease Education and Research Program at the New York University School of Medicine, in New York City, told Medscape Medical News.

"We're able to show that those problems are very real in the sense that they are presaging something which is going to emerge," he added.

"Something is going on, and our patients are telling us this, and we need to take it seriously," agreed Gary W. Small, MD, professor of psychiatry and director of the University of California, Los Angeles, Longevity Center at the Semel Institute for Neuroscience and Human Behavior.

Dr Reisberg said a further examination of his original data on SCI from 2010 showed that its predictions are holding up.

Landmark Study

In that 2010 prospective, 7-year study (Alzheimers Dement. 2010 Jan;6:11-24), Dr Reisberg and his colleagues found that patients with SCI had a 4.5 times greater risk for decline when compared with persons with no cognitive impairment (NCI), and that they declined 60% faster than patients with NCI.

Dr Reisberg has been conducting further longitudinal studies with that population. He examined a group of 98 patients who were healthy at baseline, aside from the presence of SCI (stage 2 on the Global Deterioration Scale). They were followed for a mean of 2 years. Two thirds remained at stage 2 and were considered to have SCI. Twenty percent progressed to mild cognitive impairment (MCI), and 2% progressed to dementia or Alzheimer’s disease.

"We found that the subjects declined at virtually exactly the rate that we had predicted," he said. The rate of decline over 2 years was 6.701% ― almost the same as the 6.7% predicted by the original study.

Both the GDS and the Brief Cognitive Rating Scale (BCRS) were used in the 2-year study, but the BCRS was the more sensitive measure of cognitive decline. Results on psychometeric tests and the Mini–Mental State Examination did not show significant changes over the length of the trial.

Dr Reisberg said the 2-year data should help investigators who are examining ways to mitigate SCI progression.

The cumulative data show that cognitive symptoms "may emerge 22 years before mild dementia," he said.

It may still be too soon to screen all patients for cognitive problems, but physicians can treat SCI in those who do show symptoms, he said. "There are studies that show that exercise and proper diet seem to be helpful," said Dr Reisberg, who added that he is currently studying some of those interventions in SCI.

"Let's give Dr Reisberg credit for coming up with these ideas and systematically having these hypotheses and doing the longitudinal studies," said Dr Small. The data from Dr Reisberg's studies show "that there are big differences when you start looking carefully at these groups," he said.

APOE Confirmed as SCI Risk Factor

Yonas E. Geda, MD, professor of neurology and psychiatry at the Mayo Clinic, Scottsdale, Arizona, presented data assessing risk for SCI in cognitively normal patients who either were or were not carriers for the apolipoprotein E ε4 allele (APOE).

He and colleagues conducted a case-control study derived from the Arizona APOE Cohort Study. The participants, aged 21 years or older, were recruited from the community from 1994 to 2007 using advertising. All participants underwent neuropsychologic testing and APOE genotyping.

The case participants were APOE ε4 carriers, whereas the control participants did not have the gene. SCI was assessed using the Memory Frequency questionnaire. An individual with a score of less than 7 was considered to have SCI. There were 47 carriers and 67 control individuals; 68% of carriers were women, compared with 76% of control persons. Carriers had slightly more education ― 17 years vs 16 ― but the researchers adjusted for that difference, said Dr Geda.

Overall, 93% of the carriers were found to be at risk for SCI, compared with 80% of the control persons. The risk rose greatly with age, with 100% of carriers found to be at risk, compared with 77% of control individuals.

The study "contributes to the growing body of research identifying APOE ε4 as an important risk factor for cognitive decline and Alzheimer's disease," said Dr Geda.

Dr Small said that Dr Geda's research highlights the importance of differentiating between a risk factor and an early marker of disease. Although early markers may change over time, having APOE ε4 — a risk factor — means that by age 70 years, "you're going to have SCI," Dr Small said.

Dr Reisberg is the developer and the copyright holder for the GDS and the BCRS, and that he receives research support from the National Institute of Aging, the Louis J. Kay and June E. Kay Foundation, the Hagedorn Foundation, Mrs Miriam Glaubach and Dr Felix Glaubach, and the Stringer Foundation. Dr Small is on the speaker's bureau for Activis, Forum Pharmaceuticals, Novartis, Herbalife, Janssen, and Pfizer, and is a consultant for Activis, Forum, Cogniciti, Herbalife, Lilly, Janssen, and Pfizer. He is also a shareholder in TauMark LLC and receives research support from Pom Wonderful. Dr Geda has disclosed no relevant financial relationships.

American Association for Geriatric Psychiatry (AAGP) 2016 Annual Meeting: Session 302, presented March 19, 2016.


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