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INTRODUCTION: Word‐list recall tests are routinely used for cognitive assessment, and process scoring may improve their accuracy. We examined whether Alzheimer's Disease Assessment Scale–Cognitive subscale (ADAS‐Cog) derived, process‐based digital cognitive biomarkers (DCBs) at baseline predicted Clinical Dementia Rating (CDR) longitudinally and compared them to standard metrics. METHODS: Analyses were performed with Alzheimer's Disease Neuroimaging Initiative (ADNI) data from 330 participants (mean age = 71.4 ± 7.2). We conducted regression analyses predicting CDR at 36 months, controlling for demographics and genetic risk, with ADAS‐Cog traditional scores and DCBs as predictors. RESULTS: The best predictor of CDR at 36 months was M, a DCB reflecting recall ability (area under the curve = 0.84), outperforming traditional scores. Diagnostic results suggest that M may be particularly useful to identify individuals who are unlikely to decline. DISCUSSION: These results suggest that M outperforms ADAS‐Cog traditional metrics and supports process scoring for word‐list recall tests. More research is needed to determine further applicability with other tests and populations. Highlights: Process scoring and latent modeling were more effective than traditional scoring.Latent recall ability (M) was the best predictor of Clinical Dementia Rating decline at 36 months.The top digital cognitive biomarker model had odds ≈ 90 times greater than the top Alzheimer's Disease Assessment Scale–Cognitive subscale model.Particularly high negative predictive value supports literature on cognitive testing as a useful screen.Consideration of both cognitive and pathological outcomes is needed. [ABSTRACT FROM AUTHOR]

Objective: Process-based scores of episodic memory tests, such as the recency ratio (Rr), have been found to compare favourably to, or to be better than, most conventional or "traditional" scores employed to estimate memory ability in older individuals (Bock et al., 2021; Bruno et al., 2019). We explored the relationship between process-based scores and hippocampal volume in older adults, while comparing process-based to traditional story recall-derived scores, to examine potential differences in their predictive abilities. Methods: We analysed data from 355 participants extracted from the WRAP and WADRC databases, who were classified as cognitively unimpaired, or exhibited mild cognitive impairment (MCI) or dementia. Story Recall was measured with the Logical Memory Test (LMT) from the Weschler Memory Scale Revised, collected within twelve months of the magnetic resonance imaging scan. Linear regression analyses were conducted with left or right hippocampal volume (HV) as outcomes separately, and with Rr, Total ratio, Immediate LMT, or Delayed LMT scores as predictors, along with covariates. Results: Higher Rr and Tr scores significantly predicted lower left and right HV, while Tr showed the best model fit of all, as indicated by AIC. Traditional scores, Immediate LMT and Delayed LMT, were significantly associated with left and right HV, but were outperformed by both process-based scores for left HV, and by Tr for right HV. Conclusions: Current findings show the direct relationship between hippocampal volume and all the LMT scores examined here, and that process-based scores outperform traditional scores as markers of hippocampal volume. [ABSTRACT FROM AUTHOR]

Introduction: Menopausal hormone therapy (MHT), along with the apolipoprotein E (APOE) ε4 allele, has been suggested as a possible risk factor for Alzheimer's disease (AD). However, the relationship between MHT and cerebrospinal fluid (CSF) biomarkers is unknown: we investigated this association, and whether APOE ε4 carrier status moderates it., Methods: In an observational study of 136 cognitively unimpaired female participants (M age  = 66.0; standard deviation = 6.3), we examined whether MHT use alone or in interaction with APOE ε4 carrier status was associated with CSF levels of phosphorylated tau (p-tau), amyloid beta (Aβ)40, Aβ42, p-tau/Aβ42, and Aβ42/40 ratios., Results: Significant interactions were found between APOE ε4 and MHT use for CSF biomarkers. APOE ε4 carriers who were MHT users showed worse levels of CSF p-tau/Aβ42 and Aβ42/40 ratios than all other users and non-users., Discussion: The presence of both APOE ε4 and MHT may be associated with elevated amyloid deposition and AD pathology in this sample of participants who demonstrated high familial AD risk., Highlights: Significant interactions were found between apolipoprotein E (APOE) ε4 and menopausal hormone therapy (MHT) use for cerebrospinal fluid (CSF) phosphorylated tau (p-tau)/amyloid beta (Aβ)42 and Aβ42/40 ratios. APOE ε4 carriers who were MHT users showed worse levels of CSF biomarkers than non-users and non-carriers, both users and non-users. Younger age at MHT initiation was associated with worse levels of the p-tau/Aβ42 and Aβ42/40 ratios in carriers only. The presence of both APOE ε4 carriage and MHT use may be associated with elevated amyloid deposition and AD pathology. Further studies with larger sample sizes are necessary to confirm the differences observed in the current study., (© 2025 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Introduction: Word-list recall tests are routinely used for cognitive assessment, and process scoring may improve their accuracy. We examined whether Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) derived, process-based digital cognitive biomarkers (DCBs) at baseline predicted Clinical Dementia Rating (CDR) longitudinally and compared them to standard metrics., Methods: Analyses were performed with Alzheimer's Disease Neuroimaging Initiative (ADNI) data from 330 participants (mean age = 71.4 ± 7.2). We conducted regression analyses predicting CDR at 36 months, controlling for demographics and genetic risk, with ADAS-Cog traditional scores and DCBs as predictors., Results: The best predictor of CDR at 36 months was M, a DCB reflecting recall ability (area under the curve = 0.84), outperforming traditional scores. Diagnostic results suggest that M may be particularly useful to identify individuals who are unlikely to decline., Discussion: These results suggest that M outperforms ADAS-Cog traditional metrics and supports process scoring for word-list recall tests. More research is needed to determine further applicability with other tests and populations., Highlights: Process scoring and latent modeling were more effective than traditional scoring. Latent recall ability (M) was the best predictor of Clinical Dementia Rating decline at 36 months. The top digital cognitive biomarker model had odds ≈ 90 times greater than the top Alzheimer's Disease Assessment Scale-Cognitive subscale model. Particularly high negative predictive value supports literature on cognitive testing as a useful screen. Consideration of both cognitive and pathological outcomes is needed., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

We propose a novel method to assess delayed primacy in the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) memory test. We then examine whether this measure predicts post mortem Alzheimer's disease (AD) neuropathology in individuals who were clinically unimpaired at baseline. A total of 1096 individuals were selected from the Rush Alzheimer's Disease Center database registry. All participants were clinically unimpaired at baseline, and had subsequently undergone brain autopsy. Average age at baseline was 78.8 (6.92). A Bayesian regression analysis was carried out with global pathology as an outcome; demographic, clinical, and apolipoprotein E ( APOE) data as covariates; and cognitive predictors, including delayed primacy. Global AD pathology was best predicted by delayed primacy. Secondary analyses showed that delayed primacy was mostly associated with neuritic plaques, whereas total delayed recall was associated with neurofibrillary tangles. Sex differential associations were observed. We conclude that CERAD-derived delayed primacy is a useful metric for early detection and diagnosis of AD in unimpaired individuals., Highlights: We propose a novel method to analyse serial position in the CERAD memory test.We analyse data from 1096 individuals who were cognitively unimpaired at baseline.Delayed primacy predicts post mortem pathology better than traditional metrics., Competing Interests: The authors declare no conflicts of interest. Author disclosures are available in the supporting information, (© 2024 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.)

Introduction: We propose a novel method to assess delayed primacy in the CERAD memory test. We then examine whether this measure predicts post mortem Alzheimer's disease (AD) neuropathology in individuals who were clinically unimpaired at baseline., Methods: A total of 1096 individuals were selected from the Rush Alzheimer's Disease Center database registry. All participants were clinically unimpaired at baseline, and had subsequently undergone brain autopsy. Average age at baseline was 78.8 (6.92). A Bayesian regression analysis was carried out with global pathology as outcome; demographic, clinical and APOE data as covariates; and cognitive predictors, including delayed primacy., Results: Global AD pathology was best predicted by delayed primacy. Secondary analyses showed that delayed primacy was mostly associated with neuritic plaques, whereas total delayed recall was associated with neurofibrillary tangles., Discussion: We conclude that CERAD-derived delayed primacy is a useful metric for early detection and diagnosis of AD in unimpaired individuals., Competing Interests: No author reports any conflicts of interests or disclosures.