Relationship between age and severity of cognitive impairment at diagnosis for early‐onset and late‐onset Alzheimer's disease: Comparison of LEADS and ADNI

INTRODUCTION: Recent work has identified unique cognitive profiles for early-onset Alzheimer's disease (EOAD) relative to late-onset Alzheimer's disease (LOAD), however, examination has been limited in determining whether the association between age and cognitive severity at presentation also differs across conditions. METHODS: A series of linear spline regression models was conducted across baseline cognitive data from 325 EOAD and 314 LOAD participants, after accounting for education, sex, and apolipoprotein ε4 status. RESULTS: Significant differences existed in the relationship between baseline age and cognitive performance between EOAD and LOAD samples for Processing Speed/Attention, Executive Functioning, and Episodic Immediate Memory. Younger participants from both EOAD and LOAD groups performed disproportionately worse on non-amnestic cognitive domains, with this occurring to a greater extent in EOAD than LOAD. DISCUSSION: In the age of disease-modifying treatments, results highlight the importance of assessing for cognitive declines in individuals starting much earlier than age 65. HIGHLIGHTS: Early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD) participants each displayed cognitive impairments relative to same-aged peers across most domains. Both groups displayed positive relationships between impairment among non-amnestic cognitive domains and baseline age. This relationship displayed a significantly greater effect in EOAD than LOAD, with domains of Processing Speed/Attention and Executive Functioning skills being the most pronounced. Of those participants developing AD, age displayed a disproportionate impact on their symptom onset.