Can the ‘worried well’ detect cognitive decline before objective diagnostic tests

UC Davis Professor of Neurology Sarah Tomaszewski Farias has been awarded a $3.3 million five-year grant from The National Institute on Aging to study if cultural differences affect how people perceive cognitive changes as they age. This perceived cognitive aging is referred to as subjective cognitive decline (SCD).

"Subjective cognitive decline is when an older person feels their cognition is getting worse, but when we test them using neuropsychological tests, they're still performing within the normal range," explained Tomaszewski Farias, a leader in studying cognitive decline in older adults.

Understanding subjective cognitive decline may have important implications for healthcare providers.

"There was a lot of clinical lore around what we used to call the 'worried well.' These were people that had cognitive complaints but did fine on cognitive testing. It was thought that they were depressed or anxious and often their complaints were dismissed," Tomaszewski Farias said.

However, studies have shown that SCD can be a risk factor to developing more objective cognitive decline. That includes potentially mild cognitive impairment or Alzheimer's dementia. Current SCD research suffers from three main issues:

• The overlapping symptoms of SCD and depression: People who are depressed can feel like their memory is poor. The common symptoms might obscure the right diagnosis.
• Lack of representation: SCD research as a risk for Alzheimer's disease has been studied mainly in highly educated, white people.
• Lack of longitudinal studies: Most of the studies were done at only one point in time rather than over time.

Tomaszewski Farias' new study will look at how SCD in a diverse group of older adults is associated with objective cognitive outcomes and risk for dementia. It will follow people over time to see if any participants with subjective cognitive concerns go on to develop objective cognitive impairment and dementia.

Methodology

The study will examine around 4,000 participants who are at least 55 years old. It will utilize a longitudinal cohort in the UC Davis Alzheimer's Disease Research Center, where Tomaszewski Farias is the clinical core leader. Research will also use three cohorts of Kaiser Permanente patients led by Professor of Neurology and Public Health Sciences Rachel Whitmer (Life After 90, KHANDLE and STAR).

In addition to measuring subjective and objective cognitive decline, the study will examine brain scans and blood samples for biomarkers of Alzheimer's disease and cerebrovascular disease.

Types of subjective cognitive decline that might show up differently across groups

SCD can be linked to different cognitive concerns.

"The term subjective cognitive decline doesn't specify the nature or the types of cognitive concerns that people have," Tomaszewski Farias explained. "It may be important to learn if people are reporting mainly memory concerns, or cognitive changes relating to thinking, like executive functions."

Tomaszewski Farias elaborated: If people are seeing a lot of memory problems, then that may be a sign of early Alzheimer's disease. Whereas if people have more executive difficulties, like multitasking, working memory, processing speed-related deficits, then that may fit more with cerebrovascular disease.

To measure subjective cognitive decline, the team will use the Everyday Cognition (ECog) scale. ECog is a widely used questionnaire developed by Tomaszewski Farias and UC Davis researchers two decades ago that was recently updated. It includes memory-related questions, such as whether someone is forgetting recent events and language items, such as difficulty finding words. It will also ask about spatial abilities, like navigating in one's environment, and executive functions, such as multitasking and planning for daily activities.

The new study will ask: Are there types of subjective complaints that are linked to specific diseases? And if so, could these complaints help to predict future illness?

"We will look at ways to efficiently identify people who are at increased risk for early Alzheimer's disease and other forms of cognitive decline," Tomaszewski Farias said.

Cultural differences and clinical implications

There's a lot to disentangle, said Tomaszewski Farias. "One size is probably not going to fit all in terms of identifying the red flags of subjective cognitive decline. It may be very culturally dependent in terms of how people express what they are noticing in their cognitive abilities."

The study will look at the extent to which people are worried about the subjective changes versus chalking it up to normal aging. Studies have shown that some people are picking up something that was missed on their cognitive testing. They are noticing internal changes that clinicians can't yet see on the testing.

It is still unclear how far in advance people start noticing these changes before a clinical diagnosis can be made. Research indicated that the closest is probably 5 to 10 years before a diagnosis.

"For clinicians, we hope to better figure out or define what are the subjective types of complaint that are a bigger red flag than others," Tomaszewski Farias said.