Association Between Age and Cognitive Severity in Participants from the Longitudinal Early‐Onset Alzheimer’s Disease Study

Abstract

AbstractBackgroundAge‐related cognitive declines are well‐documented in cognitively normal adults (van der Willik et al., 2021), as are greater cognitive impairments with advancing age in traditional‐ (or “late‐”) onset Alzheimer’s disease (LOAD; Davis et al., 2018). Early‐onset Alzheimer’s disease (EOAD; diagnosis ≤65 years old) possesses a unique disease course and underlying pathology relative to LOAD (Mendez, 2012), consequently it is unknown if the association between age and cognitive severity is similar. The objective of the current study is to examine the relationship between cognition and age‐at‐baseline in participants enrolled in the Longitudinal Early‐Onset Alzheimer’s Disease Study (LEADS; Apostolova et al., 2019).MethodCross‐sectional cognitive data from 371 participants (aged 40‐64) enrolled in the LEADS protocol were analyzed, using composites for the domains of Episodic Memory, Speed/Attention, Visuospatial skills, Language, and Executive skills. Relationships between age‐at‐baseline and cognition were examined using linear regression based on diagnostic group classification (cognitively normal [CN], amyloid‐positive EOAD, and amyloid‐negative Early‐Onset non‐Alzheimer’s disease [EOnonAD]), controlling for the effects of age and education years.ResultDemographic characteristics for each group are shown in Table 1. Across cognitive domains, the CN group displayed either non‐significant or negative relationships (Executive skills; r = ‐0.30, p = .006) between age‐at‐baseline and cognitive performance (Figure 1 and Table 2). Conversely, the EOAD group showed consistent positive relationships for domains of Speed/Attention (r = 0.23, p<.001), Visuospatial Skills (r = 0.19, p = .01), and Episodic Memory (r = 0.16, p = .02). A similar non‐significant trend was observed for the EOnonAD group for Speed/Attention (r = 0.17, p = .19). When considering those with amnestic‐variant early‐onset dementia across diagnostic groups, positive relationships between age‐at‐baseline and cognition were observed for Speed/Attention (r = 0.19, p = .006) and Visuospatial skills (non‐significant trend; r = 0.14, p = .05), but not for Episodic Memory (r = ‐0.06, p = .35).ConclusionWorse cognitive severity was associated with younger age‐at‐baseline for EOAD participants in LEADS. Similar trends were observed for EOnonAD participants, though to a lesser magnitude. These results were counter to those observed for CN participants, and to what is known about cognitive trajectories in normal aging or LOAD. These findings further support previous suggestions that EOAD appears to be a distinct entity relative to LOAD.