Memory Complaints Could Signal Dementia Decades Later

Pauline Anderson

October 29, 2015

Older women who perform normally on a standard cognitive test but who have subjective memory complaints (SMCs) are significantly more likely to have a memory disorder almost two decades later, a new study shows.

The strongest association was when SMCs were uncovered just a few years before the cognitive evaluation.

Although SMCs have been linked to cognitive impairment in the past, this study was among the first to look at the association over such a long period.

The findings suggest that SMCs are an early warning sign of future dementia, said lead author Allison Kaup, PhD, clinical research psychologist, San Francisco Veterans Affairs Medical Center, and assistant professor, Department of Psychiatry, University of California at San Francisco.

"It's important to ask older patients whether they have concerns about their memory," said Dr Kaup. If they do have such complaints, "doctors should pay attention" and follow those patients closely over time, "watching out for future more significant problems."

The study was published online October 28 in Neurology.

The analysis included 1107 female participants in the prospective Study of Osteoporosis Fractures who were aged 65 years and older. The cohort was cognitively normal (defined by a modified Mini-Mental State Examination [mMMSE] score of no more than 1.5 standard deviations below the mean compared to age- and education-matched peers).

They were assessed for SMC 2 years after baseline (year 2) and at years 6, 10, and 16. As part of the Geriatric Depression Scale questionnaire, they were asked a simple yes-or-no question: "Do you feel you have more problems with memory than most?"

At baseline, 8.0% of the participants endorsed SMCs. Compared with those without baseline SMCs, women with SMCs had lower education, greater myocardial infarction (MI) history, and more depressive symptoms.

Cognitive Assessment

At year 20 of the study (18 years after the baseline SMC assessment), participants were determined by an expert panel to have normal cognition, mild cognitive impairment, or dementia.

Women with baseline SMCs were more likely to be diagnosed with cognitive impairment at year 20 compared with women without baseline SMC (52.8% vs 38.0%; P = 0.01).

Baseline SMCs were significantly associated with increased risk for cognitive impairment even after adjustment for demographic characteristics0, baseline mMMSE score, history of MI, and depressive symptoms (adjusted odds ratio [OR], 1.7; 95% confidence interval [CI], 1.1 - 2.8; P = .03).

The effect of SMC was unchanged after exclusion of 26 patients with baseline depression (OR, 1.7; 95% CI, 1.01 - 2.8; P = .046).

There seemed to be an important timing pattern, with a stronger association between SMC and cognitive impairment showing up closer to the cognitive assessment (adjusted OR 4 years before assessment, 3.0; 95% CI, 1.8 - 5.0; P < .001).

"We found that when we looked at folks who had memory complaints a few years before the diagnostic assessment — so just 4 years between those two assessments — those memory complaints were more strongly associated. People might be noticing more things about their own memory closer in time to when they start showing clear memory impairment."

This generally fits the pattern of the memory impairment process being gradual and developing over time before eventually becoming noticeable, she said.

A limitation of the study, acknowledged Dr Kaup, was that it didn't differentiate between different types of dementia. "Women completed a variety of different neuropsychological tests and measures at the end of study, and those results and data were reviewed by a panel of clinical experts who diagnosed them as either meeting criteria for mild cognitive impairment or dementia. Those two diagnoses don't tell us specifically whether it might be Alzheimer's disease dementia or another type."

Another limitation, she said, was that the study didn't have repeated clinical assessments throughout the study. "So we can't know for certain exactly when someone crossed that threshold from just having memory concerns to actually showing memory impairment."

And the question used by the study to assess SMC may be open to different interpretations. Other studies have used different questions and means to assess memory complaints, noted Dr Kaup. "There is no gold standard at this point about how to best assess it."

However, researchers are proposing more consistency across studies, she said. It might prove useful in future studies, she added, to specify whether an individual feels he or she has more memory problems compared with most people their age, and whether this is something new for them personally.

"In our study, we don't have that level of detail, and I wish we did, but we thought it was still striking that we found an association even with this very simple question."

It's a question that's relatively easy for clinicians to incorporate into their practice.

Although there aren't yet treatments for dementia, there are proven lifestyle strategies clinicians can recommend that help reduce risks. These include exercise, staying socially and mentally active, and getting enough sleep, said Dr Kaup.

Real-Life Experience

Reached for a comment, Neelum Aggarwal, MD, associate professor, neurology, Rush University Medical Center, Chicago, Illinois, said the study results reflect "real-life," everyday encounters in the clinic and the community.

"The complaint of having memory issues or worsening memory is very common and unfortunately, physicians are not sure how far to investigate this issue. Likewise, family members aren't sure what to make of these complaints, as they are so common, so they're often overlooked."

Although the confounders included in the study, such as medical conditions and depression (an important covariate because depression is twice as common in women as in men), were "reasonable," Dr Aggarwal said. She would like to know more about the participants' marital status, sleep patterns, and lifestyle factors, such as history of smoking, alcohol, and falls.

She also would like more information about specific cardiovascular risk factors. "For example, myocardial infarction was noted to be higher in those complaining of SMCs. This is not surprising as we know that cardiovascular risk factors can be related to memory issues."

As well, the duration of these risk factors — for example, when the MI occurred and the number of MIs — would have been interesting to examine, said Dr Aggarwal, who started the Cardio Cognitive Clinic at Rush.

The study's suggestion that losing mental "sharpness" and becoming forgetful can be noted early on, even without overt symptoms on testing, corresponds to the known science regarding changes in brain, that amyloid deposition can occur many years before symptoms, noted Dr Aggarwal.

As for the simple assessment of SMC used in the study, she said questions normally try to capture how long a memory complaint has been going on. An example she used was: "Do you feel that your memory/thinking has changed over the last 5 to 10 years? (yes/no)."

She noted that having a question that simply asks how people are performing compared with others may produce bias. "It may have people view their 'overall functioning' compared to their peers. Often people will say they are doing okay and not getting at the real issue of cognitive problems."

The Study of Osteoporotic Fractures is supported by National Institutes of Health funding. The National Institute on Aging (NIA) provides support under the following grants. The research was also supported in part by an NIA grant (awarded to Kristine Yaffe, MD); by a Career Development Award (awarded to Allison Kaup, PhD) from the US Department of Veterans Affairs, Rehabilitation Research and Development Service; and by the Department of Veterans Affairs Office of Academic Affiliations Advanced Fellowship Program in Mental Illness Research and Treatment, the Medical Research Service of the San Francisco Veterans Affairs Medical Center, and the Department of Veterans Affairs Sierra-Pacific Mental Illness Research, Education, and Clinical Center. Dr Kaup and Dr Aggarwal have disclosed no relevant financial relationships.

Neurology. Published online October 28, 2015. Abstract

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