Associations of Stages of Objective Memory Impairment with Cerebrospinal Fluid and Neuroimaging Biomarkers of Alzheimer’s Disease

Objective: To investigate cerebrospinal fluid (CSF) and neuroimaging correlates of Stages of Objective Memory Impairment (SOMI) based on Free and Cued Selective Reminding Test (FCSRT) performance, and to evaluate the effect of APOE ε4 status on this relationship. Methods: Data from 586 cognitively unimpaired individuals who had FCSRT, CSF, and volumetric magnetic resonance imaging (MRI) measures available was used. We compared CSF measures of β-amyloid (Aβ42/Aβ40 ratio), phosphorylated tau (p-Tau181), total tau (t-Tau), hippocampal volume, and PIB-PET mean cortical binding potential with partial volume correction (MCBP) among SOMI groups in the whole sample and in subsamples stratified by APOE ε4 status. Results: Participants had a mean age of 67.4 (SD=9.1) years, had 16.1 (SD=2.6) years of education, 57.0% were female, and 33.8% were APOE ε4 positive. In the entire sample, there was no significant difference between SOMI stages in Aβ42/Aβ40 ratio, p-Tau181, t-Tau, or PIB-PET MCBP when adjusted for age, sex, and education. However, higher SOMI stages had smaller hippocampal volume (F=3.29, p=0.020). In the stratified sample based on APOE ε4 status, in APOE ε4 positive individuals, higher SOMI stages had higher p-Tau181 (F=2.94, p=0.034) higher t-Tau (F=3.41, p=0.019), and smaller hippocampal volume (F=5.78, p<0.001). There were no significant differences in CSF or imaging biomarkers between SOMI groups in the APOE ε4 negative subsample. Conclusion: Cognitively normal older individuals with higher SOMI stages have higher in-vivo tau and neurodegenerative pathology only in APOE ε4 carriers. These original results indicate the potential usefulness of the SOMI staging system in assessing of tau and neurodegenerative pathology.