Selective loss of episodic memory of odor percepts is associated with progression to amnestic MCI or Alzheimer’s disease in cognitively healthy seniors

Abstract

AbstractBackgroundAccumulating evidence indicates that the pathological changes of AD begin 15 years prior to symptom onset. There is an unmet need for accessible, affordable, and accurate means to screen cognitively normal individuals for preclinical AD. We previously developed the Percepts of Odor Episodic Memory (POEM) test battery, which assesses identification, memory and discrimination of odor percepts. In a pilot study, we demonstrated that elderly individuals with odor memory scores that fell below the 50% confidence intervals of the memory scores predicted by their odor discrimination and odor identification scores; these individuals were deemed “at risk” for progression to mild cognitive impairment and AD based on an enrichment in biomarkers for AD.MethodWe tested our olfactory “at risk” status as a predictor of future decline by administering the POEM test battery to 61 older individuals who were cognitively normal (CN) or expressed subjective cognitive concerns (SCC) and were followed longitudinally in the Massachusetts Alzheimer’ s Disease Research Center. These individuals were added to our original sample of 140 participants who had undergone olfactory testing. A Cox Proportional Hazards model was used in a subset of this expanded cohort (n=127) who were followed over an average of 4.22 years to determine whether the olfactory “at risk” status predicted a risk of clinical progression to a diagnosis of amnestic MCI or Alzheimer’s disease.Result28% of the CN and SCC participants followed longitudinally were deemed “at risk” based on a selective odor memory loss. These “at risk” participants demonstrated a higher risk of progressing to amnestic MCI or AD (HR = 3.45, (95% CI:1.13‐10.72, p=0.0278) over time while controlling for age, education, and sex. The effect of Group (CN vs SCC) and its interaction with “at risk” status were not significant.ConclusionOur results indicate that probing olfactory function with a threshold based on personalized identification and discrimination abilities identifies cognitively healthy seniors who progress to amnestic MCI or AD at faster rate over time. Future work is focused on developing a remote version of this test for self‐administration that can be used to screen cognitively healthy individuals for research studies and clinical trials.