Awareness of Memory Decline Drops Years Before Dementia

Pauline Anderson

August 28, 2015

Awareness of memory impairment starts deteriorating about 2.6 years before a diagnosis of dementia, a new study shows.

Researchers also found that this deterioration is a manifestation of dementia-related pathology, such as tau tangles and gross cerebral infarcts.

"It's important to try to understand what the process of dementia is and what it feels like from the inside out," said lead author Robert Wilson, PhD, professor, Neuropsychology, Rush University Alzheimer Disease Center, Chicago, Illinois.

The study was published online August 26 in Neurology.

The analysis was based on data from three ongoing longitudinal clinical pathologic studies of older patients who at the time of enrollment were at least 50 years old and did not have cognitive impairment.

These studies included the Religious Orders Study, which began in 1994 and includes older Catholic nuns, priests, and brothers across the United States; the Rush Memory and Aging project, which got underway in 1997 and includes older people from the Chicago area; and the Minority Aging Research Study, which started in 2004 and enrolls older black people from metropolitan Chicago.

Every year, study participants underwent a battery of 19 cognitive tests, including measures of episodic memory, semantic memory, and working memory. At every annual exam, they were also asked how often they had trouble remembering things and how their memory compared to a decade before.

The researchers put together a composite rating of how participants thought their memory was and compared this with their actual performance on memory tests over time.

Mismatch Measure

"We sort of got a measure of the mismatch between their rating and their performance each year," said Dr Wilson. "Statistically, if that number is 0, it means there is a pretty good correspondence between their rating and performance. As it dips down below 0, they are over-rating their memory."

The analysis included 2092 participants, who had a mean baseline age of 76.1 years and a mean of 7.7 years of follow-up. In this group, this "mismatch" measure at baseline was a mean of 0.016, which suggested no systematic tendency to overestimate or underestimate memory ability at that time.

Researchers looked at a subset of 239 participants with at least four annual evaluations who developed dementia. They determined that starting a mean of 2.6 years before their dementia onset, their episodic memory awareness began to sharply decline.

"We found that there was a drop-off in their awareness of their memory problems that on average occurred 2 to 3 years before they were diagnosed with dementia," said Dr Wilson.

Awareness of memory decline decreased a little earlier in younger patients than older ones, a finding that was unexpected, said Dr Wilson.

It might be that younger people don't expect to have memory problems but such problems are "normative" among older patients, he said. "When you're 60, the most expected thing is that you don't have memory problems but when you're 90, it's expected that your memory is not great."

There was no association between memory awareness and sex or education.

Researchers looked at a global measure of memory performance that incorporated semantic memory and working memory as well as episodic memory. The results of this analysis were "quite similar" to those of episodic memory, said Dr Wilson.

Researchers also looked at the association between memory awareness and pathology in a subset of 385 participants who died and had a brain autopsy. After accounting for individual differences in three neuropathologies that were associated with more rapid decline in episodic memory awareness — tau, gross infarcts, and transactive response DNA-binding protein 43 (TDP-43) — there was no decline in memory awareness.

As Dr Wilson explained, TDP-43 is the primary protein abnormality in amyotrophic lateral sclerosis and in some forms of frontotemporal dementia and is found at autopsy in very old people. "It's a naturally occurring protein but at some point migrates and aggregates," he said.

The new results "suggest pretty strongly that these pathologies are really driving loss of awareness of memory dysfunction," said Dr Wilson.

"Both from a clinical and from a pathological standpoint, we concluded that loss of awareness of memory impairment is really part of the natural history of late-life dementia; it's driven by these pathologies and it progresses as we see people developing dementia clinically."

New Insights

The new results provide some insight into what can be a baffling condition. For example, most people who develop dementia don't develop depression at the same time.

"They're really not that aware of the devastating loss that has occurred and that's probably in some ways a good thing," said Dr Wilson.

The new study, he added, suggests there may be some truth to the old clinical rule of thumb that if you have memory problems but are still worried about them, you're probably still okay.

Asked to comment on the study for Medscape Medical News, Judy Willis, MD, media liaison, American Institute of Neurology, said this new research "supports the current value that neurologists place on cognitive testing as part of routine neurological examinations."

It's important, she said, that clinicians include a history of cognitive decline as part of the yearly physical evaluations required by Medicare. "This will ensure that a medical expert judges cognition in elderly patients instead of counting on possibly unreliable self-reports," said Dr Willis.

She stressed that although there's no decisive intervention to alter the progression of late-life dementia, early detection is important to ongoing intervention research. "And this will be essential when such an intervention is found," she said.

The study was supported by the National Institute on Aging and the Illinois Department of Public Health. Dr Wilson serves as a consulting editor for the journals Aging, Neuropsychology, and Cognition; Psychology and Aging; and Neuropsychology. He has served as a consultant for Pain Therapeutics Inc and receives research support from the National Institutes of Health, the Alzheimer's Association, and Zinfandel Pharmaceuticals. Dr Willis has disclosed no relevant financial relationships.

Neurology. Published online August 26, 2015. Abstract

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