Predicting Cognitive Decline in Amyloid-Positive Patients With Mild Cognitive Impairment or Mild Dementia.

BACKGROUND AND OBJECTIVES: Cognitive decline rates in Alzheimer disease (AD) vary greatly. Disease-modifying treatments 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. METHODS: From the Amsterdam Dementia Cohort, we selected amyloid-positive participants with MCI or mild dementia and at least 2 longitudinal Mini-Mental State Examination (MMSE) measurements. Amyloid positivity was based on CSF AD biomarker concentrations or amyloid PET. We used linear mixed modeling to predict MMSE over time, describing trajectories using a cubic time curve and interactions between linear time and the baseline predictors age, sex, baseline MMSE, APOE ε4 dose, CSF ß-amyloid (Aß) 1-42 and pTau, and MRI total brain and hippocampal volume. Backward selection was used to reduce model complexity. These models can predict MMSE over follow-up or the time to an MMSE value. MCI and mild dementia were modeled separately. Internal 5-fold cross-validation was performed to calculate the explained variance (R2). RESULTS: In total, 961 participants were included (age 65 ± 7 years, 49% female), 310 had MCI (MMSE 26 ± 2) and 651 had mild dementia (MMSE 22 ± 4), with 4 ± 2 measurements over 2 (interquartile range 1-4) years. Cognitive decline rates increased over time for both MCI and mild dementia (model comparisons linear vs squared vs cubic time fit; p < 0.05 favoring a cubic fit). For MCI, backward selection retained age, sex, and CSF Aß1-42 and pTau concentrations as time-varying effects altering the MMSE trajectory. For mild dementia, retained time-varying effects were Aß1-42, age, APOE ε4, and baseline MMSE. R2 was 0.15 for the MCI model and 0.26 for mild dementia in internal cross-validation. A hypothetical patient with MCI, baseline MMSE 28, and CSF Aß1-42 of 925 pg/mL was predicted to reach an MMSE of 20 after 6.0 years (95% CI 5.4-6.7) and after 8.6 years with a hypothetical treatment reducing decline by 30%. DISCUSSION: We constructed models for MCI and mild dementia that predict MMSE over time. These models could inform patients about their potential cognitive trajectory and the remaining uncertainty and aid in conversations about individualized potential treatment effects.

Impact of COVID-19 pandemic on mortality rate in memory clinic patients.

INTRODUCTION: We investigated whether mortality in memory clinic patients changed due to coronavirus disease 2019 (COVID-19) pandemic. METHODS: We included patients from the Amsterdam Dementia Cohort: (1) n = 923 pandemic patients (baseline visit: 2017-2018, follow-up: until 2021), and (2) n = 830 historical control patients (baseline visit: 2015-2016, follow-up: until 2019). Groups were well-balanced. We compared mortality during pandemic with historical control patients using Cox regression. Differences in cause of death between groups were explored using Fisher's exact test. RESULTS: Pandemic patients had a higher risk of mortality than historical control patients (hazard ratio [HR] [95% confidence interval {CI}] = 1.34 [1.05-1.70]). Stratified for syndrome diagnosis, the effect remained significant in dementia patients (HR [95% CI] = 1.35 [1.03-1.78]). Excluding patients who died of COVID-19-infection, the higher mortality risk in pandemic patients attenuated (HR [95% CI] = 1.24 [0.97-1.58]). Only the difference in cause of death between pandemic patients and historical control patients for death to COVID-19-infection (p = 0.001) was observed. CONCLUSION: Memory clinic patients had increased mortality risk during COVID-19 compared to historical control patients, attributable to dementia patients. Highlights: We investigated if mortality rates in memory clinic patients changed due to COVID-19 pandemic.We included patients along the cognitive continuum, including SCD, MCI, and dementia.We used a well-balanced historical control group.Memory clinic patients had higher risk for mortality during COVID-19 lockdown.Our results indicate that excess mortality is mainly caused by death to COVID-19 infection.