SERIAL POSITION EFFECT AS A BIOMARKER IN THE DIFERENTIAL DIAGNOSIS OF MILD COGNITIVE IMPAIRMENT: A MULTIMODAL BIOMARKERS APROACH
Background: Diagnostic accuracy of mild cognitive impairment (MCI) is important for prognosis, i.e. identifying individuals at risk of progression to Alzheimer's disease (AD) We previously divided ADNI MCI cases into those who were or were not also impaired on a second test the Rey Auditory Verbal Learning Test (AVLT) The 3 year rate of progression to AD was dramatically different in the AVLTand AVLT+ subgroups (51% vs 16% p<.001) and CSF Ab and tau levels were significantly different. It may seem obvious that those who are impaired on both tests are more likely to progress to AD because they are more impaired and are probably being captured at a later point along their disease trajectory. However, there is an equally plausible explanation, namely, that the low progression rate in the AVLT+ group is because requiring only a single test to define impairment results in an excess of false positive diagnoses. More AD biomarker pathology in the AVLTgroup is uninformative because it is consistent with either explanation. We differentiated the two alternatives by comparing genetic risk for AD. Methods: Participants were 318 ADNI MCI cases (93 AVLT+ 225 AVLT AD polygenic risk scores (AD PRSs) were based on International Genomics of Alzheimer's Project (IGAP) data adjusted for principal components to account for population stratification. We also adjusted for age. Logistic regression analyses examined odds ratios (ORs) of being AVLT Results: After adjusting for age (OR1/40.67, 95% CI1/40.52 0.86, p<.002) a higher AD PRS was associated with significantly increased odds of being in the AVLTgroup (OR1/42.00, 95% CI1/41.41 2.83) Conclusions: If the difference in having only 1 versus >1 test impaired is basically a matter of when we happen to capture people along their illness trajectories, then the MCI subgroups should not differ in their genetic risk for AD. However, MCI defined by impairment on 2+ memory tests was at significantly greater genetic risk based on AD PRSs. Thus, the lower progression rate in the AVLT+ group likely reflects excess false positive diagnoses rather than earlier MCI. Requiring impairment on just 1 additional memory test can substantially improve the accuracy of MCI diagnosis and prognosis.
Alzheimer's Dementia