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Background: Despite decades of research, the mechanisms linking APOE to Alzheimer's disease (AD) remain poorly understood. Finding additional risk variants at the APOE locus, beyond the common APOE‐ε2 and APOE‐ε4 alleles, may help elucidate how APOE is involved in the disease. Method: Association with case‐control status was tested in a sequenced discovery sample (Stage 1) and followed‐up in several microarray imputed cohorts as well as the UK Biobank whole‐exome sequencing resource using a proxy‐AD phenotype (Stages 2+3) (Table 1). Stage 1 included 37,409 non‐unique participants of European or Admixed‐European ancestry, with 11,868 cases and 11,934 controls passing analysis inclusion criteria. In Stages 2+3, 475,473 participants were considered across 8 cohorts, of which 56,029 cases, 28,484 proxy‐AD cases, and 328,372 healthy‐controls passed inclusion criteria, and were of European ancestry. Result: Two missense variants were associated with a two to three‐fold decreased AD risk: R251G (odds ratio, 0.44; 95% confidence interval [CI], 0.33‐0.59; P = 4.7×10‐8) and V236E (odds ratio, 0.37; 95% CI, 0.25‐0.56; P = 1.9×10‐6) (Table 2, Figures 1, 2). Additionally, the cumulative incidence of AD in carriers of these variants was found to grow more slowly with age compared to non‐carriers (Table 3). Conclusion: We identified a novel variant associated with AD, R251G, which mitigates the ε4 associated AD risk, and confirmed the protective effect of the V236E variant. The location of the variants confirms that the carboxyl‐terminal portion of apoE plays an important role in AD pathogenesis. The large risk reductions reported here, suggest that protein chemistry and functional assays of these variants have the potential to identify novel pathways for drug development. [ABSTRACT FROM AUTHOR]

Background: A previous survey conducted among the European Alzheimer´s Disease Consortium (EADC) of academic memory clinics showed mild propensity (65%) towards implementing the clinician's Uniform Dataset (cUDS), a standard cognitive assessment consistent with the US Uniform Dataset‐3rd, to diagnose mild cognitive impairment (MCI). Currently, in Italy translation and adaptations of the cUDS is in progress. Here, we evaluate the cUDS implementation feasibility in Italian academic and non‐academic settings. Method: The 382 clinicians affiliated to the Italian Society of Neurology on Dementia (SINDem) were invited to complete the EADC online survey translated into Italian, investigating centers current practices, acceptability and feasibility of cUDS implementation. We used a mixed‐methods design to perform descriptive statistics, logistic regressions and qualitative analysis of clinicians' comments to investigate hurdles, facilitators and mechanisms impacting implementation. Result: Sixty‐two clinicians participated from 14 of the 20 Italian regions. Response rates were unevenly distributed: 56% from Northern, 16% Central and 27% Southern regions (χ2(1) = 39, p =.0005). Centers were equally distributed among academic (48%) and non‐academic (52%) institutions(χ2(1) = 30, p =.899), had a variable yearly patient flow (M = 454;SD = 686) and mainly offered neurological (90%) and psychological (87%) services. 88% reported to use formal definitions for the diagnosis of MCI. 10% of academic and 30% of non‐academic clinicians reported full reimbursement of assessment. Fifty‐nine responders (95%) expressed willingness to implement cUDS. The most frequent facilitators were the availability of neuropsychologists(26%) and of tests' material(23%). 42% of non‐academic clinicians envisioned no specific barrier; 12% envisioned lack of neuropsychologists training, 12% cultural issues and 12% unavailability of local norms. 24% of academic clinicians identified time‐economic factors as barriers. Conclusion: Our data showed very high acceptability for cUDS. Lower need of cross‐compatibility with previous standard might explain the higher acceptability in SINDem compared to EADC. Indeed, EADC clinicians are more reluctant due to the lack of compatibility and digital tools supporting harmonization with local datasets. Similar to EADC, SINDem academic clinicians reported the need for tests' material, but neuropsychologists' training‐availability and finances were considered more important in Italy. Despite the small sample size, these results inform the design of future implementation in SINDem memory clinics. [ABSTRACT FROM AUTHOR]

A case of transient global amnesia has been neuropsychologically assessed during the attack. Global involvement of any memory modalities and far-reaching retrograde amnesia were found. Follow-up retesting, 1 week and 6 months later, showed persistence of mild verbal memory impairment.