The Stages of Objective Memory Impairment (SOMI) system predicted transitions from normal cognition to incident symptomatic cognitive impairment, longitudinal data showed.
Over a mean follow-up of about 6 years, cognitively normal older adults with memory tests scores reflecting moderate retrieval impairment (SOMI-2) were twice as likely to progress to incident cognitive impairment as those whose memory was intact (SOMI-0), according to Ellen Grober, PhD, of Albert Einstein College of Medicine in the New York City and co-authors.
Participants with memory storage deficits (SOMI-3 or SOMI-4) were three times as likely to progress, the researchers reported in Neurology. After adjusting for all biomarkers, SOMI stage remained an independent predictor of incident cognitive impairment.
"There is increasing evidence that some people with no thinking and memory problems may actually have very subtle signs of early cognitive impairment," Grober said in a statement.
"In our study, a sensitive and simple memory test predicted the risk of developing cognitive impairment in people who were otherwise considered to have normal cognition," she added. "Our results support the use of the SOMI system to identify people most likely to develop cognitive impairment."
Earlier studies have linked SOMI outcomes with the presence of Alzheimer's disease pathology in cognitively unimpaired people in the Anti-Amyloid Treatment in Asymptomatic Alzheimer's (A4) clinical trial.
SOMI is based on the Free and Cued Selective Reminding Test (FCSRT). The test begins with a study phase in which people are shown four cards, each with drawings of four items, and are asked to identify an item belonging to a particular category (for example, an apple would belong to the fruit category). Participants are then asked to recall the items; if they're stuck, they're given category cues to prompt them.
"The FCSRT provides measures of memory retrieval (free recall) and memory storage (total recall)," Grober and co-authors wrote. "Free recall scores predict incident mild cognitive impairment and incident dementia, particularly dementia due to Alzheimer's disease, and often outperform other cognitive tests."
The SOMI system maps free recall and total recall scores into stages. At SOMI-0, free recall and total recall are normal. SOMI-1 and SOMI-2 reflect increasing retrieval difficulty with declining free recall in the context of intact total recall, beginning 7-8 years before clinical dementia. In SOMI-3 and SOMI-4, cuing fails to recover all the items missed in free recall, indicating a memory storage deficit occurring about 1 to 3 years before clinical dementia.
Grober and colleagues followed 969 cognitively normal people from the Knight Alzheimer Disease Research Center in St. Louis who had a Clinical Dementia Rating (CDR) of 0 at baseline. Mean age was about 69, mean follow-up was 6.36 years, and 59.6% were female.
About a third (33.8%) of participants were APOE4 positive. A total of 555 people had cerebrospinal fluid and structural MRI measures (the biomarker subgroup) and 144 were amyloid-positive. Findings were adjusted for age, sex, education, and APOE4 status.
Participants in SOMI-1 through SOMI-4 had elevated hazard ratios for transitioning from normal cognition to symptomatic cognitive impairment, which was defined as CDR≥0.5.
SOMI-2 (HR 2.07, 95% CI 1.32-3.01) and SOMI-3/4 (HR 3.11, 95% CI 1.94-4.97) were significantly associated with incident cognitive impairment compared with SOMI-0 (P<0.001 for both). In subgroups with biomarkers and amyloid-positive status, SOMI-1 participants also showed increased cognitive impairment risk.
In models including measures of amyloid and tau pathology and hippocampal volume, SOMI remained a significant predictor of time to CDR≥0.5.
Only 4.9% of participants (47 people) were classified as SOMI-3 or SOMI-4, limiting interpretation of data from this group, Grober and co-authors said. Most participants were white and highly educated, and results may not apply to others.
Disclosures
The study was funded by the NIH, the Alzheimer's Association, Cure Alzheimer Fund, and the Leonard and Sylvia Marx Foundation.
Grober receives a small royalty for commercial use of the Free and Cued Selective Reminding Test with Immediate Recall; the test is available at no cost to researchers and clinicians. One co-author disclosed relationships with AbbVie, American Academy of Neurology, American Headache Society, Amgen, Biohaven, Eli Lilly, GlaxoSmithKline, Grifols, Lundbeck, Merck, Pfizer, Teva, Vector, and Vedanta. No other relationships relevant to the manuscript were reported.
Primary Source
Neurology
Source Reference: Grober E, et al "Association of stages of objective memory impairment with incident symptomatic cognitive impairment in cognitively normal individuals" Neurology 2023; DOI:10.1212/WNL.0000000000207276.