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Background Wide evidence suggests that physical activity (PA) confers protection against Alzheimer’s disease (AD). On the other hand, the apolipoprotein E gene (APOE) ε4 allele represents the greatest genetic risk factor for developing AD. Extensive research has been conducted to determine whether frequent PA can mitigate the increased AD risk associated with APOE ε4. However, thus far, these attempts have produced inconclusive results. In this context, one possible explanation could be that the influence of the combined effect of PA and APOE ε4 carriage might be dependent on the specific outcome measure utilised. Main body. In order to bridge these discrepancies, the aim of this theoretical article is to propose a novel model on the interactive effects of PA and APOE ε4 carriage on well-established mechanisms underlying AD. Available literature was searched to investigate how PA and APOE ε4 carriage, independently and in combination, may alter several molecular pathways involved in AD pathogenesis. The reviewed mechanisms include amyloid beta (Aβ) and tau deposition and clearance, neuronal resilience and neurogenesis, lipid function and cerebrovascular alterations, brain immune response and glucose metabolism. Finally, combining all this information, we have built an integrative model, which includes evidence-based and theoretical synergistic interactions across mechanisms. Moreover, we have identified key knowledge gaps in the literature, providing a list of testable hypotheses that future studies need to address. Conclusions We conclude that PA influences a wide array of molecular targets involved in AD neuropathology. A deeper understanding of where, when and, most importantly, how PA decreases AD risk even in the presence of the APOE ε4 allele will enable the creation of new protocols using exercise along pharmaceuticals in combined therapeutic approaches., Ministry of Science and Innovation, Spain (MICINN) Spanish Government PRE2019-087612

Background Accurate data on the types of healthcare people seek in the early stages following mild traumatic brain injury (mTBI) in Australia is lacking. We sought to investigate the types of healthcare people seek following mTBI, including seeking no care at all; ascertain the demographic, pre- and peri-injury factors, and symptom characteristics associated with the care that people access; and examine whether choice of care is associated with symptomatic recovery and quality of life. Methods An online retrospective survey of Australians aged 18 to 65 years who had experienced a self-reported ‘concussion’ (mTBI) within the previous 18 months. Types of healthcare accessed were investigated, as well as those who did not seek any care. Data were analysed using frequency and percentages, chi-squared tests and logistic regression models. Results A total of 201 respondents had experienced a self-reported ‘concussion’ but 21.4% of the respondents did not seek any care. Of the 183 respondents who sought healthcare, 52.5% attended a hospital Emergency Department, 41.0% attended a general practitioner and 6.6% accessed sports-based care. Compared to their counterparts, those who had a lower level of education (p = 0.001), had experienced previous mTBI (p = 0.045) or previous mental health issues (p = 0.009) were less likely to seek healthcare, whilst those who had experienced loss of consciousness (p = 0.014), anterograde (p = 0.044) or retrograde (p = 0.009) amnesia, and symptoms including drowsiness (p = 0.005), nausea (p = 0.040), and feeling slow (p = 0.031) were more likely to seek care. Those who did not seek care were more likely to recover within one month (AOR 4.90, 95%CI 1.51 – 15.89, p = 0.008), albeit the relatively large 95%CI warrants careful interpretation. Compared to seeking care, not seeking care was not found to be significantly associated with symptom resolution nor quality of life (p > 0.05). Conclusions This study provides unique insight into factors associated with healthcare utilisation in the early stages following mTBI, as well as outcomes associated with choice of care, including not seeking care. Delivering targeted community education on the signs and symptoms of mTBI, and the advantages of seeking care following injury is an important step forward in the management of this challenging condition.