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Background: Alzheimer’s disease (AD) was biologically defined by the 2018 NIA-AA Research Framework (RF), which recommends dichotomously defining biomarker status as normal or abnormal with single cutpoints. However, a three-range approach remains unexplored in AD fluid biomarkers. Objective: To assess the prognostic utility of a three-range approach for CSF biomarkers in AD. Methods: We included 1278 non-demented individuals (CU: n=575; MCI: n=703) from the ADNI with baseline CSF Elecsys® biomarkers. Within it, we defined three-range cutpoints with two-graph receiver operating characteristics (TGROC) for each CSF biomarker (Aβ1-42, p-tau, p-tau/Aβ1-42), based on amyloid PET positivity. Then, linear mixed-effects and Cox proportional hazards models were used to estimate longitudinal cognitive trajectories and risk of clinical progression based on CSF biomarker status. Hereby derived three-range cutpoints were compared to previously described binary thresholds for the same biomarkers. Power analyses for simulated trials were also carried. Results: We observed dynamic amyloid-PET changes for participants in the intermediate range, while a static profile for clearly normal and abnormal groups. Longitudinally, our approach revealed a divergent intermediate cognitive trajectory undetected by dichotomization, with power analyses demonstrating potential applications for trial enrichment. Conclusion: The proposed approach can improve CSF-based diagnosis, refine prognostic assessment and enhance clinical trial recruitment.

Background: It is not fully understood how vascular risk factors (VRFs) are associated with Alzheimer’s disease (AD) pathology to promote neurodegeneration and cognitive decline. Objective: Investigate whether VRF burden synergistically interacts with AD pathology to accelerate neurodegeneration and cognitive decline in cognitively unimpaired (CU) individuals. Methods: We assessed 503 CU participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. Individuals were dichotomized as having an elevated VRF burden if ≥ 2 VRFs (V+) and as presenting biological AD if CSF p-tau181 ≥ 24 pg/mL and CSF Aβ1-42 ≤ 976.6 pg/mL [(AT)+]. Neurodegeneration was assessed with plasma neurofilament light (NfL) and cognition with the modified version of the Preclinical Alzheimer’s Cognitive Composite. Results: Linear mixed-effects models demonstrated that an elevated VRF burden interacted with AD pathology to promote higher rates of neurodegeneration (β=5.68, p=.005) and cognitive decline (β=- 0.43, p=.019). Survival analysis demonstrated that only (AT)+V+ individuals had a significantly greater risk of clinical progression to cognitive impairment (adjusted Hazard Ratio=3.5, p

Background: Subjective Cognitive Decline may represent the earliest clinical manifestation of the Alzheimer’s continuum. A continental-size country like Brazil demands regionalized strategies to provide adequate public health strategies. Objectives: To analyze the prevalence of SCD in Brazilian regions, sex and genders. Methods: Data was gathered from a complex-sample epidemiological study named ELSI (Estudo Longitudinal da Saúde de Idosos). SCD criteria was applied within the dataset. Weighting for complex-sampling was performed. Data was analyzed according to national region, sex and gender. Results: Overall nationwide prevalence of SCD was 15.48%. Prevalence of SCD was the highest in Midwest (19.9%), followed by Northeast (17%), North (16.9%), South (14.6%) and Southeast (14.2%, p