Conference Coverage

Subjective Cognitive Decline: The Earliest Sign of Alzheimer’s Disease?


BOSTON—In recent years, a growing body of research has identified subjective cognitive decline (SCD) as a precursor to mild cognitive impairment (MCI) and potentially the earliest clinical sign of Alzheimer’s disease. While researchers are quick to point out that not every individual with characteristics suggestive of SCD will necessarily progress to Alzheimer’s disease, recognition of the condition has important clinical implications not only for patients and their physicians, but also for identifying a new target population of subjects for clinical trials in the prevention of Alzheimer’s disease.

At the 2013 Alzheimer’s Association International Conference (AAIC), researchers presented the results of several clinical studies on SCD and a report on what may be the first international initiative to conceptualize what clinical trial investigators should be looking at when studying SCD. Findings include the following:

• In a study of 189 clinically normal individuals older than 65, investigators at Brigham and Women’s Hospital and elsewhere correlated the patients’ subjective cognitive concerns about their memory and everyday life on several questionnaires with their amyloid brain scans and found that the greater amount of concerns individuals had was related to a greater amount of amyloid buildup in their brains—and therefore possibly a greater risk for eventual progression to Alz­heimer’s disease.

• In an examination of the role of subjective memory complaints as predictors of serious cognitive impairment in approximately 530 subjects (mean age at baseline, 73.2) enrolled in the Biologically Resilient Adults in Neurological Studies (BRAINS) at the University of Kentucky, investigators asked each participant if he or she had perceived any changes in memory since the previous visit. For the end point of the age at which either a dementia or MCI occurred, 72.5% of 160 converters reported a change in memory before the transition, versus 48.8% of the nonconverters, leading the study’s authors to conclude that a subjective memory complaint is predictive of transition to a seriously impaired cognitive state within six to eight years.

• Subjective memory impairment in more than 2,300 healthy elderly patients was found to specifically predict decline in episodic memory over eight years. Investigators at the University of Bonn in Germany and elsewhere analyzed data from six waves of the primary-care-based, prospective longitudinal AgeCoDe study.

• According to the SCD-Initiative, an international working group founded in November 2012 to develop a common framework for research on SCD in preclinical Alzheimer’s disease, the available data are too limited and too heterogeneous to define SCD in preclinical Alzheimer’s disease as a clear-cut entity, highlighting the need for intensified research on this topic.

The interest in SCD reflects a shift in the field of dementia research: by determining now who might be at risk for developing Alzheimer’s disease in the future, clinicians may be able to intervene earlier in the etiology of the disorder—once disease-modifying therapies are developed—making it more likely that such treatments will be effective.

SCD may be one of the more subtle signals pointing Alzheimer’s disease researchers in that direction, said Ronald Petersen, MD, PhD, Professor of Neurology and Director of the Mayo Alzheimer’s Disease Research Center at the Mayo Clinic College of Medicine in Rochester, Minnesota.

“The whole field of Alzheimer’s disease research has moved from the dementia stage of a decade or so ago to the MCI stage, where people are partially symptomatic, and now we’re even talking about a pre-MCI stage—that is, the people are clinically normal when they’re evaluated, but they’re expressing some concern over a change in their cognitive function,” he said. “When should somebody be concerned that this is just not incidental forgetfulness of aging but maybe a harbinger of something more serious? We clearly don’t want to worry everybody who’s aging. At the same time I think the public and clinicians need to be aware that individuals who have these concerns might, in fact, be telling us something that we need to understand and use in our clinical context.”

A Heightened Awareness
Several of the presenters emphasized that these findings have to be interpreted carefully so as to not confuse normal aging with progression to dementia. “These results are not meant to worry the public that, if they forget where their keys are, they’re on the path to Alzheimer’s disease,” said Rebecca Amariglio, PhD, a clinical neuropsychologist at Brigham and Women’s Hospital in Boston and lead author of the study involving amyloid brain scans. “Some signs that I think would be typical of normal aging are walking into a room and forgetting why; maybe having trouble remembering the names of people that they’ve only met once or twice; noticing a change relative to when they were young adults—[when] these changes are spanning over many years, if not decades; and that, when asking friends or people of the same age that these changes seem to be pretty consistent with other people the same age.


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