Abstract INTRODUCTION Although cerebrospinal fluid (CSF) biomarkers reflect neurodegeneration in Alzheimer's disease (AD), it remains unclear whether these biomarkers track neurodegeneration in early‐onset Alzheimer's disease (EOAD). METHODS In 80 EOAD patients, we examined correlations between eight CSF biomarker levels and cortical thickness decreases within the EOAD cortical atrophy signature. Significant correlations were then entered into a multiple regression analysis. We also examined contributions of EOAD atrophy and CSF biomarkers to cognitive impairment. RESULTS The levels of four CSF biomarkers correlated to EOAD signature atrophy. Stepwise regression analyses revealed that CSF neurofilament light chain (NfL) levels best predicted EOAD signature atrophy. Multiple regression showed EOAD signature atrophy combined with CSF NfL levels explained more variance in cognitive impairment than either factor alone. DISCUSSION Within EOAD patients, CSF NfL levels relate to the magnitude of cortical atrophy, and a combination of EOAD signature atrophy and CSF NfL levels most robustly predict cognitive impairment.
Relationship between age and severity of cognitive impairment at diagnosis for early‐onset and late‐onset Alzheimer's disease: Comparison of LEADS and ADNI
Alzheimer's & Dementia | January 30, 2026 | Volume: 22 | Issue: 2 | Pages: No page available
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.