BOSTON – Patients who complain of memory and cognition problems may be experiencing early, subtle signs of Alzheimer’s disease, according to findings from four separate studies presented at the Alzheimer’s Association International Conference 2013.
A study of 2,319 elderly patients with no dementia at baseline and no mild cognitive impairment (MCI) showed that patients who reported subjective memory impairment (SMI) had a significantly greater decline than control subjects in episodic memory (immediate and delayed recall), and that patients with SMI with self-reported concerns about memory had a greater slope of decline, reported Alexander Koppara, a PhD candidate at the Universitätsklinikum Bonn in Germany.
Mr. Alexander Koppara
Depression also was associated with cognitive performance at baseline, but the effects of SMI remained when the investigators controlled for depression, he said.
"Even if we introduce depression as a covariate of development over time, depression is not a significant predictor of cognitive decline, which is in line with a lot of findings in psychiatry. That is why subjects who report subjective memory impairment should be tracked over a long period of time," Mr. Koppara said.
He added that a multimodal approach combining studies of biomarkers with experimental assessment tools could help to further objectify clinical impressions from subjective memory and cognition symptoms.
Amyloid mirrors memory concerns
The findings of Mr. Koppara’s group were supported by a second study indicating that, among 200 healthy, clinically normal older adults, those who reported more concerns than their nonworried peers about problems with cognition and memory had more evidence of beta-amyloid protein buildup in the brain, as seen with PET scans with the amyloid tracing agent 11C-labeled Pittsburgh Compound B.
In addition, among subjects with higher levels of education and reading ability, the greater the level of concern, the greater the degree of amyloid deposition, said Rebecca E. Amariglio, Ph.D., a clinical neuropsychologist at Brigham & Women’s Hospital and Massachusetts General Hospital in Boston.
"We also took a look at reports of concerns by an informant, or somebody who knew these subjects well, like a family member or a friend, and we did not see a relationship with amyloid," she said at a media briefing. "There seems to be something specific to someone’s own knowledge of their abilities that isn’t quite captured by an informant at this stage, the preclinical stage of Alzheimer’s disease."
Dr. Rebecca E. Amariglio
Dr. Amariglio emphasized that many subjective memory changes should not be cause for concern. For example, it’s normal for an older person to walk into a room and forget why he or she went there, have difficulty retrieving names of unfamiliar people, or have changes in memory, compared with young adulthood.
What is abnormal, and may be a trigger for clinical evaluation, is getting lost in familiar surroundings, having difficulty remembering important details of recent events, trouble following the plot of a TV program or book because of memory, or having noticeably worse memory than friends of the same age, she said.
Subjective symptoms in high-risk allele carriers
Dr. Amariglio was coauthor of a second study looking at women aged 70 years and older with no history of stroke who were participants in the Nurses Health Study. The investigators looked at a subjective memory symptom score based on self-report of up to seven specific, subjective memory symptoms and compared it with verbal memory decline over 6 years among 889 women with one or two copies of the high-risk apolipoprotein E epsilon-4 (APOE epsilon-4) allele and 2,972 APOE epsilon-4 noncarriers.
They found that, for both APOE epsilon-4 carriers and noncarriers, higher numbers of subjective memory symptoms at baseline were related to poorer verbal memory scores (P for trend less than .001 for both groups). In addition, after adjusting for age and the presence of depression, women with more subjective memory symptoms at baseline also had higher rates of verbal memory decline over time (P for trend = .006 for APOE epsilon-4 carriers and less than .001 for noncarriers).
Interestingly, only one subjective memory symptom at baseline was needed to accurately predict verbal memory decline over time among APOE epsilon-4 carriers, compared with three or more needed to predict decline in noncarriers.
Dr. Cecilia Samieri
"Self-report of memory concerns may be useful for identifying individuals at greater risk of memory decline, particularly within [APOE epsilon-4] carriers, a group at higher risk of memory decline and Alzheimer’s disease dementia," said lead author Cecilia Samieri, Ph.D., an epidemiologist and researcher at the University of Bordeaux in France.
Self-reported symptoms during longitudinal study