Predicting cognitive decline in amyloid‐positive patients with mild cognitive impairment or mild dementia

Abstract

AbstractBackgroundCognitive decline rates in Alzheimer’s disease (AD) vary greatly. Disease‐modifying treatments (DMT) may alter cognitive decline trajectories, rendering their prediction increasingly relevant. We aimed to construct clinically applicable prediction models of cognitive decline in amyloid‐positive patients with mild cognitive impairment (MCI) or mild dementia.MethodsFrom the Amsterdam Dementia Cohort, we selected amyloid‐positive participants with MCI (n = 317, 66±7yrs, 45%Female, baseline MMSE 26±2) or mild dementia (n = 666, 65±7yrs, 49%Female, MMSE 22±4) and ≥2 annual MMSEs. Follow‐up was 3±2yrs with 4±2 MMSEs. Amyloid positivity was based on cerebrospinal fluid (CSF) AD biomarker concentrations or amyloid PET. We used linear mixed modelling to predict MMSE over time. First, decline trajectories were described with cubic time curves (S‐shaped). Then, we backwards selected predictors from baseline MMSE, age, sex, APOE ε4 dose, magnetic resonance imaging (MRI; visual scores: medial temporal lobe [MTA], global atrophy), CSF concentrations (phosphorylated tau [pTau], Aβ1‐42), and their interactions with linear time. MCI and mild dementia were modelled separately as stratification increased log‐likelihood.ResultsFor MCI and mild dementia, rates of cognitive decline increased over time. In MCI, average MMSE declined from 26.4(95%CI:26.2‐26.7) to 25.8(25.5‐26.1) after 18 months, to 24.2(23.7‐24.6) after three years, and to 21.0(20.1‐21.7) after five years. In mild dementia, MMSE declined from 22.4(95%CI:22.0‐22.6) to 19.8(19.4‐20.2), 15.3(14.6‐15.9), and 7.8(6.7‐8.9). For MCI, selected predictors of future MMSE were baseline MMSE, and interactions of time with age, MTA and pTau (table 1). For mild dementia, additional selected interactions with time were baseline MMSE, Aβ1‐42, and APOE ε4. Figure 1 shows the predicted decline distribution. As an example; predicted MMSE after three years for a 65yrs female MCI patient with baseline MMSE 27, would be 26.3 with MTA 0 and pTau 20pg/ml, compared to 23.8 with MTA 1 and pTau 40pg/ml (figure 2a;2b). In the latter case, 27% slower decline would lengthen follow‐up to a predicted MMSE of twenty by fourteen months.ConclusionWe constructed models for MCI and mild dementia that predict MMSE over time. These models could inform patients about their potential cognitive trajectory and aid in conversations about DMT initiation and the evaluation of their potential effect.