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Alzheimer's disease (AD) and osteoporosis are two diseases that mainly affect elderly people, with increases in the occurrence of cases due to a longer life expectancy. Several epidemiological studies have shown a reciprocal association between both diseases, finding an increase in incidence of osteoporosis in patients with AD, and a higher burden of AD in osteoporotic patients. This epidemiological relationship has motivated the search for molecules, genes, signaling pathways and mechanisms that are related to both pathologies. The mechanisms found in these studies can serve to improve treatments and establish better patient care protocols.

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While Alzheimer's disease (AD) diagnosis, management, and care have become priorities for healthcare providers and researcher's worldwide due to rapid population aging, epidemiologic surveillance efforts are currently limited by costly, invasive diagnostic procedures, particularly in low to middle income countries (LMIC). In recent years, wastewater-based epidemiology (WBE) has emerged as a promising tool for public health assessment through detection and quantification of specific biomarkers in wastewater, but applications for non-infectious diseases such as AD remain limited. This early review seeks to summarize AD-related biomarkers and urine and other peripheral biofluids and discuss their potential integration to WBE platforms to guide the first prospective efforts in the field. Promising results have been reported in clinical settings, indicating the potential of amyloid ß, tau, neural thread protein, long non-coding RNAs, oxidative stress markers and other dysregulated metabolites for AD diagnosis, but questions regarding their concentration and stability in wastewater and the correlation between clinical levels and sewage circulation must be addressed in future studies before comprehensive WBE systems can be developed.

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OBJECTIVE: To analyze the consumption of drugs for Alzheimer's disease on the Brazilian private market and its geographical distribution from 2014 to 2020. METHODS: National data from the Brazilian National System of Controlled Product Management were used, regarding sales of donepezil, galantamine, rivastigmine, and memantine from January 2014 to December 2020. Sales data were used as a proxy for drug consumption and expressed as defined daily dose/1,000 inhabitants/year at national, regional, federative unit and microregion levels. RESULTS: Drug consumption went from 5,000 defined daily doses/1,000 inhabitants, in 2014, to more than 16,000/1,000 inhabitants, in 2020, and all federative units showed positive variation. The Brazilian Northeast had the highest cumulative consumption in the period but displayed microregional disparities while the North region had the lowest consumption. Donepezil and memantine were the most consumed drugs, with the highest growth in consumption from 2014 to 2020. CONCLUSION: The consumption of medicines indicated to treat Alzheimer's disease tripled in Brazil between 2014 and 2020, which may relate to the increase in the prevalence of the disease in the country, greater access to health services, and inappropriate use. This challenges managers and healthcare providers due to population aging and the increased prevalence of chronic-degenerative diseases.

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•The study investigated the prevalence of certain comorbidities in patients with Chagas megaoesophagus compared to those without the condition, aiming to determine whether it serves as a protective or risk factor. •In the general group (546 patients), the three most prevalent comorbidities were hypertension (44.3%), dyslipidaemia (17.8%), and heart failure (15.2%). •In the older group (248 patients), similar to that in the general group, the most prevalent comorbidities were hypertension, dyslipidaemia, and heart failure. •The lower prevalence of diabetes mellitus and Alzheimer's disease in the patients with Chagas megaoesophagus suggests the association of enteric nervous system denervation and requires further investigation. Objective - This study aimed to evaluate the prevalence of some epidemiologically important comorbidities in patients with Chagas megaoesophagus in relation to the population without megaoesophagus, and whether this condition would be a protective or a risk factor for the conditions analysed. Methods - This observational descriptive study collected data from the medical records of patients with a previous diagnosis of megaoesophagus (timing: from 2005 to 2020). The patients were divided by age into a general (all ages) and an older group (aged 60 years or more). Associations were searched for four main areas/systems/involvements: cardiovascular, respiratory, endocrine and neurological. Results - The general group included 546 patients and the older group included 248 patients. As for the prevalence of comorbidities in the general group, the three most prevalent diseases were hypertension, with 44.3% (CI95%: 40.21-48.51%); dyslipidaemia, with 17.8% (CI95%: 14.79-21.19%); and heart failure, with 15.2% (CI95%: 12.43-18.45%). Similar to that in the general group, the most prevalent comorbidities in the group of older patients were hypertension, dyslipidaemia, and heart failure. Conclusion - Systemic arterial hypertension, dyslipidaemia, and heart failure were the most prevalent comorbidities in this population. The lower prevalence of diabetes mellitus and Alzheimer's disease suggests the association of enteric nervous system denervation and requires further investigation.

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BACKGROUND: Despite the high burden of Alzheimer's disease and other dementias among the Hispanic population worldwide, little is known about how dementia affects healthcare utilizations among this population outside of the US, in particular among those in the Caribbean region. OBJECTIVE: This study examines healthcare utilization associated with Alzheimer's disease and other dementias among older adults in the Caribbean as compared to the US. METHODS: We conducted harmonized analyses of two population-based surveys, the 10/66 Dementia Group Research data collected in Dominican Republic, Cuba, and Puerto Rico, and the US-based Health and Retirement Study. We examined changes in hospital nights and physician visits in response to incident and ongoing dementias. RESULTS: Incident dementia significantly increased the risk of hospitalization and number of hospital nights in both populations. Ongoing dementia increased the risk of hospitalization and hospital nights in the US, with imprecise estimates for the Caribbean. The number of physician visits was elevated in the US but not in the Caribbean. CONCLUSIONS: The concentration of increased healthcare utilization on hospital care and among patients with incident dementia suggests an opportunity for improved outpatient management of new and existing dementia patients in the Caribbean.

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BACKGROUND: The SARS-CoV2 global pandemic impacted participants in the Alzheimer's Prevention Initiative (API) Autosomal Dominant Alzheimer's Disease (ADAD) clinical trial, who faced three stressors: 1) fear of developing dementia; 2) concerns about missing treatment; and 3) risk of SARS-CoV2 infection. OBJECTIVE: To describe the frequency of psychological disorders among the participants of the API ADAD Colombia clinical study, treated by a holistic mental health team during the COVID-19 pandemic. The extent of use of mental health team services was explored considering different risk factors, and users and non-users of these services were compared. METHODS: Participants had free and optional access to psychology and psychiatry services, outside of the study protocol. Descriptive statistics was used to analyze the frequency of the mental health difficulties. A multivariable logistic regression model has been used to assess associations with using this program. RESULTS: 66 participants were treated by the Mental Health Team from March 1, 2020, to December 31, 2020. Before and after the start of the pandemic, the most common psychological problems were anxiety (36.4% before, 63.6% after) and depression (34.8% before, 37.9% after). 70% of users assisted by psychology and 81.6% of those assisted by psychiatry felt that the services were useful for them. Female sex, depression, and anxiety before the pandemic were positively associated with being assisted by either psychology or psychiatry, while the association with hyperlipidemia was negative. CONCLUSIONS: A holistic mental health program, carried out in the context of a study, could mitigate psychopathology during pandemics such as COVID-19.

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A few epidemiological studies are evaluating the prevalence and mortality rates of Alzheimer's disease, with no one using a nationwide sample of Brazilian elderlies. This study aims to calculate the prevalence of Alzheimer's disease and investigate possible associations with sociodemographic and lifestyle factors and the presence of diseases non-communicable, and the prevalence and mortality for all Brazilian state capitals. This is an ecological design study made with secondary public data provided by the Ministry of Health. Prevalence rates were calculated based on the analysis of the dispensing of Alzheimer's disease-specific drugs. Correlation analyzes were performed between rates and factors, and a multiple linear regression analysis was used to analyze possible associations between variables, controlled for each other. AD prevalence was 313/100,000. Prevalence rates were positively associated with primary health care coverage factors and negatively associated with ultra-processed food consumption and physical activity levels. AD mortality was 98/100,000. Mortality rates were positively associated with the proportion of obese elderly and elderly living on up to half the minimum wage and were inversely associated with the proportion of elderly with diabetes factors. We found positive and negative associations of sociodemographic, behavioral and diabetes indicators with Alzheimer's disease prevalence and mortality, which provide data that can be investigated by studies with different designs.

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BACKGROUND: Fear of falling (FoF) is a condition associated with falls, multi-morbidity, and functional impairment. To date it remains unknow which clinical, somatic, socio-demographic, behavioral, and emotional factors are associated with FoF and how these factors interact in people with Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD). OBJECTIVE: Identify the association of FoF with clinical, socio-demographic, and neuropsychiatric factors in patients with AD and bvFTD. METHODS: We evaluated 98 participants, 58 with AD and 40 with bvFTD at mild or moderate stages and assess FoF using the Falls Efficacy Scale-International. Additionally, we analyzed cognitive, physical performance variables, functional impairment, and affective and behavioral symptoms associated with FoF using standardized scales and a regression model analysis. RESULTS: The prevalence of FoF in AD and bvFTD was 51% and 40%, respectively. In the AD group, physical performance [F (3, 53) = 4.318, p = 0.009], the behavioral symptoms model [F (19, 38) = 3.314, p = 0.001], and the anxiety model [F (1, 56) = 13.4, p≤0.01] showed statistically significant values. In addition, the presence of hallucinations assessed with the Neuropsychiatric Inventory and social behavior assessed with the Mild Behavioral Impairment Checklist were significant. In contrast, in the bvFTD group, a homologous group of models was evaluated but we did not find any significant results. CONCLUSION: FoF in people with AD was related to physical performance, neuropsychiatric symptoms such as apathy and hallucinations, and affective symptoms such as anxiety. However, this pattern was not seen in the bvFTD group, and therefore further studies are required.

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This Review emphasizes the impact of APOE4-the most significant genetic risk factor for Alzheimer's disease (AD)-on peripheral and neural effects starting in childhood. We discuss major mechanistic players associated with the APOE alleles' effects in humans to understand their impact from conception through all life stages and the importance of detrimental, synergistic environmental exposures. APOE4 influences AD pathogenesis, and exposure to fine particulate matter (PM2.5), manufactured nanoparticles (NPs), and ultrafine particles (UFPs) associated with combustion and friction processes appear to be major contributors to cerebrovascular dysfunction, neuroinflammation, and oxidative stress. In the context of outdoor and indoor PM pollution burden-as well as Fe, Ti, and Al alloys; Hg, Cu, Ca, Sn, and Si UFPs/NPs-in placenta and fetal brain tissues, urban APOE3 and APOE4 carriers are developing AD biological disease hallmarks (hyperphosphorylated-tau (P-tau) and amyloid beta 42 plaques (Aß42)). Strikingly, for Metropolitan Mexico City (MMC) young residents ≤ 40 y, APOE4 carriers have 4.92 times higher suicide odds and 23.6 times higher odds of reaching Braak NFT V stage versus APOE4 non-carriers. The National Institute on Aging and Alzheimer's Association (NIA-AA) framework could serve to test the hypothesis that UFPs and NPs are key players for oxidative stress, neuroinflammation, protein aggregation and misfolding, faulty complex protein quality control, and early damage to cell membranes and organelles of neural and vascular cells. Noninvasive biomarkers indicative of the P-tau and Aß42 abnormal protein deposits are needed across the disease continuum starting in childhood. Among the 21.8 million MMC residents, we have potentially 4 million APOE4 carriers at accelerated AD progression. These APOE4 individuals are prime candidates for early neuroprotective interventional trials. APOE4 is key in the development of AD evolving from childhood in highly polluted urban centers dominated by anthropogenic and industrial sources of pollution. APOE4 subjects are at higher early risk of AD development, and neuroprotection ought to be implemented. Effective reductions of PM2.5, UFP, and NP emissions from all sources are urgently needed. Alzheimer's Disease prevention ought to be at the core of the public health response and physicians-scientist minority research be supported.

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BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative condition characterized by impaired cognitive function. It results in high morbidity, including a large number of hospitalizations, and mortality, generating high costs to health systems. OBJECTIVE: The present epidemiological analysis evaluated the number of hospitalizations and deaths by AD as the main diagnosis in Brazil between 2010 and 2020. This endeavor should contribute to a better understanding of the disease and its implications. METHODS: The present analytical, observational, longitudinal, and retrospective study used data extracted from the Department of Informatics of the Brazilian Unified Health System (DATASUS, in the Portuguese acronym). The variables include the number of hospitalizations, the total cost spent, the average cost per hospitalization, the average length of hospital stay, the number of deaths during hospitalization, the mortality rate per hospitalization, sex, age group, region, and race. RESULTS: From 2010 to 2020, there were 188,811 deaths and 13,882 hospitalizations for AD, with a total expenditure of BRL 25,953,019.40 in hospitalizations. The average length of hospital stay was 25 days. Over the considered period, mortality, the number of hospitalizations, and the total cost increased while the average length of stay decreased. CONCLUSION: From 2010 to 2020, AD represented a large portion of hospital admissions, generating a significant cost to the health system and a large number of deaths. These data are important to undertake joint efforts to prevent hospitalizations of these patients in order to minimize impacts on the health system.

ANTECEDENTES: A doença de Alzheimer (DA) é uma doença neurodegenerativa caracterizada pelo comprometimento da função cognitiva. Resulta em uma alta taxa de morbimortalidade, por meio de um número significativo de óbitos e internações, gerando um alto custo ao sistema de saúde. OBJETIVO: Realizar uma análise epidemiológica, utilizando as variáveis citadas abaixo, por DA como principal diagnóstico, no Brasil, entre 2010 e 2020, a fim de contribuir para um melhor entendimento da doença e suas implicações. MéTODOS: Estudo analítico, observacional, longitudinal e retrospectivo. Os dados foram extraídos do Departamento de Informática do Sistema Único de Saúde (DATASUS). As variáveis utilizadas foram número de internações, custo total gasto, custo médio por internação, tempo médio de internação, número de óbitos nas internações, taxa de mortalidade por internação, número de óbitos absolutos, sexo, faixa etária, região e raça. RESULTADOS: De 2010 a 2020, foram registrados 188.811 óbitos e 13.882 internações por DA, com um gasto total de R$ 25.953.019,40 em internações. O tempo médio de permanência no hospital foi de 25 dias. Em 11 anos, houve aumento da mortalidade, internações e custo total; por outro lado, o tempo médio de permanência, no mesmo período, diminuiu. CONCLUSãO: A DA, nos anos avaliados, representa uma parcela significativa das internações hospitalares, gerando um custo significativo ao sistema de saúde, além do número de óbitos. Estes dados são importantes para gerar esforços conjuntos para evitar internações desses pacientes, a fim de minimizar o impacto no Sistema de Saúde.

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