Separate And Joint Effects Of Stages Of Objective Memory Impairment And Cognitive Function

Index On Clinical Progression In A4

Author Block: Priyanka Kumari¹, Richard B. Lipton^2,3, Rebecca E. Amariglio⁴, Reisa A. Sperling⁴, Ellen

Grober¹

¹Neurology, Albert Einstein College od Medicine, Bronx, NY, USA, ²Neurology, Albert Einstein College

of Medicine, Bronx, NY, USA, ³Montefiore Medical Canter, Bronx, NY, USA, ⁴Neurology, Harvard

Medical School, Boston, MA, USA.

Abstract:

Background:Only 20-30% of amyloid-positive cognitively normal individuals progress to mild

cognitive impairment (MCI) or Alzheimer’s disease (AD) within five years. Identifying amyloid positive

individuals most likely to progress will improve the efficiency of secondary prevention trials. Using data

from the Anti-Amyloid in Asymptomatic Alzheimer’s Disease (A4) study, we assessed the predictive

validity of the Stages of Objective Memory Impairment (SOMI) system, and the Cognitive Function

Index (CFI)-Self.

Methods:Among 1106 A4 participants, we identified an optimal cut score of 2.58 (Low vs High) for CFI

and applied previously determined SOMI cut scores (Table 1). Progression was defined by 2 consecutive

CDRs>0; time to progression was modelled using Cox proportional hazards regression adjusting for

age, sex, APOE ε4status and amyloid. Data were pooled across active and placebo treatment arms.

Models were fit in the full cohort, and in subsamples.

Results: Of 1106 enrolled individuals, 399 (36%) progressed and 707 (64%) did not. Baseline

characteristics are shown (Table 1). In the full cohort, the adjusted Cox model shows that that high CFI

(vs. low CFI) predicted progression (HR=1.82; 95% CI: 1.49-2.24). Using SOMI 0 as the reference, the HR

for progression for the SOMI 1 group is 1.50(95% CI:1.14-1.98) and for the SOMI 2-4 group the HR is

2.22 (95% CI: 1.69-2.91). In models including both CFI and SOMI as predictors of progression. each

made a significant independent contribution. (Table 2a). We examined the effect of SOMI in groups

with high vs low CFI. In the low CFI group, SOMI=1 (HR=1.86) and SOMI=2-4 (HR=2.61) significantly

predicted progression. In the high CFI group, SOMI (2-4) remained significant whereas SOMI-1 was not

(Table 2b). The Figure provides Kaplan-Meyer curves that show the contribution of CFI and SOMI to the

prediction of progression in amyloid positive individuals.

Conclusion: Subjective cognitive concerns and objective memory impairment separately and jointly

predict progression in amyloid positive cognitively unimpaired individuals providing complementary

information. Using both CFI and SOMI to determine eligibility for secondary prevention trials in amyloid

positive individuals may improve trial efficiency.