Mendelian randomization to evaluate the effect of folic acid supplement on the risk of Alzheimer disease.

We conducted a study to evaluate the impact of folic acid supplementation on the risk of Alzheimer disease (AD). A Mendelian randomization (MR) analysis model assessed the causal effects of folic acid supplementation on AD, utilizing data from recent genome-wide association studies. Effect estimates were scrutinized using various methods: inverse-variance weighted (IVW), simple mode, weighted mode, simple median, weighted median, penalized weighted median, and the MR-Egger method. The sensitivity analysis assessed heterogeneity and pleiotropy of individual single nucleotide polymorphisms (SNPs) using the IVW method with Cochran Q statistics and MR Egger intercept, respectively. Additionally, a leave-one-out sensitivity analysis determined potential SNP-driven associations. Both fixed-effect and random-effect IVW models in the MR analysis revealed a reduced risk of AD associated with folic acid supplementation (odds ratio, 0.930; 95% CI, 0.903-0.958, P < .001; odds ratio, 0.930; 95% CI, 0.910-0.950, P < .001) based on 7 SNPs as instrumental variables. The reverse MR analysis indicated no causal association between AD and folic acid supplementation. This study, utilizing genetic data, suggests that folic acid supplementation may potentially reduce the risk of AD and provides novel insights into its etiology and preventive measures.

The associations of serum vitamin D status and vitamin D supplements use with all-cause dementia, Alzheimer's disease, and vascular dementia: a UK Biobank based prospective cohort study.

BACKGROUND: Prior studies on vitamin D and dementia outcomes yielded mixed results and had several important limitations. OBJECTIVES: We aimed to assess the associations of both serum vitamin D status and supplementation with all-cause dementia, Alzheimer's disease (AD), and vascular dementia (VD) incidence. METHODS: With a prospective cohort study design, we comprehensively assessed the associations of vitamin D and multivitamin supplementation, as well as vitamin D deficiency {25-hydroxyvitamin D [25(OH)D] <30 nmol/L}, and insufficiency [25(OH)D 30 to <50 nmol/L], with the 14-year incidence of all-cause dementia, AD, and VD in 269,229 participants, aged 55 to 69, from the UK Biobank. RESULTS: Although 5.0% reported regular vitamin D use and 19.8% reported multivitamin use, the majority of participants exhibited either vitamin D deficiency (18.3%) or insufficiency (34.0%). However, vitamin D deficiency was less prevalent among users of vitamin D (6.9%) or multivitamin preparations (9.5%) than among nonusers (21.5%). Adjusted Cox regression models demonstrated 19% to 25% increased risk of all 3 dementia outcomes for those with vitamin D deficiency [hazard ratio (HR) 95% confidence interval (CI)]: 1.25 (1.16, 1.34) for all-cause dementia; 1.19 (1.07-1.31) for AD; 1.24 (1.08-1.43) for VD] and 10% to 15% increased risk of those with vitamin D insufficiency [HR (95% CI): 1.11 (1.05, 1.18) for all-cause dementia; 1.10 (1.02-1.19) for AD; 1.15 (1.03-1.29) for VD]. Regular users of vitamin D and multivitamins had 17% and 14% lower risk of AD [HR (95% CI): 0.83 (0.71, 0.98)] and VD [HR (95% CI): 0.86 (0.75, 0.98)] incidence, respectively. CONCLUSIONS: Although our findings indicate the potential benefits of vitamin D supplementation for dementia prevention, randomized controlled trials are essential for definitive evidence.

Diet's Role in Modifying Risk of Alzheimer's Disease: History and Present Understanding.

Diet is an important nonpharmacological risk-modifying factor for Alzheimer's disease (AD). The approaches used here to assess diet's role in the risk of AD include multi-country ecological studies, prospective and cross-sectional observational studies, and laboratory studies. Ecological studies have identified fat, meat, and obesity from high-energy diets as important risk factors for AD and reported that AD rates peak about 15-20 years after national dietary changes. Observational studies have compared the Western dietary pattern with those of the Dietary Approaches to Stop Hypertension (DASH), Mediterranean (MedDi), and Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diets. Those studies identified AD risk factors including higher consumption of saturated and total fats, meat, and ultraprocessed foods and a lower risk of AD with higher consumption of fruits, legumes, nuts, omega-3 fatty acids, vegetables, and whole grains. Diet-induced factors associated with a significant risk of AD include inflammation, insulin resistance, oxidative stress, elevated homocysteine, dietary advanced glycation end products, and trimethylamine N-oxide. The molecular mechanisms by which dietary bioactive components and specific foods affect risk of AD are discussed. Given most countries' entrenched food supply systems, the upward trends of AD rates would be hard to reverse. However, for people willing and able, a low-animal product diet with plenty of anti-inflammatory, low-glycemic load foods may be helpful.

Habitual glucosamine use, APOE genotypes, and risk of incident cause-specific dementia in the older population.

BACKGROUND: The relationship of glucosamine use with incident dementia in the older population remains uncertain. We aimed to evaluate the longitudinal association between habitual glucosamine supplement and the risk of cause-specific dementia and examine the possible effect modifiers on this association. METHODS: The study included 214,945 participants over the age of 60 who had available information on glucosamine use and did not have dementia at baseline in the UK Biobank. The APOE genotypes were determined by a combination variant of rs429358 and rs7412. The primary outcome was incident vascular dementia, incident Alzheimer's disease, and incident frontotemporal dementia, respectively. RESULTS: Over a median follow-up duration of 12 years, 1039, 1774, and 122 participants developed vascular dementia, Alzheimer's disease, and frontotemporal dementia, respectively. Overall, habitual glucosamine use was significantly associated with a lower risk of incident vascular dementia (adjusted HR, 0.82; 95%CI, 0.70-0.96), but not significantly associated with incident Alzheimer's disease (adjusted HR, 1.02; 95%CI, 0.92-1.14) and incident frontotemporal dementia (adjusted HR, 0.95; 95%CI, 0.63-1.43). Moreover, the inverse association between habitual glucosamine use and incident vascular dementia was more pronounced in participants with concomitant supplement of calcium (P-interaction = 0.011), and those without concomitant supplement of zinc (P-interaction = 0.018). However, APOE ε4 dosage and baseline cognitive function did not significantly modify the relationships of glucosamine use with incident vascular dementia or Alzheimer's disease (All P-interactions > 0.05). CONCLUSIONS: Regardless of APOE genotypes and baseline cognitive function, habitual glucosamine use was significantly inversely associated with incident vascular dementia in the older population.

Psychological Status of the Participants in Alzheimer's Prevention Initiative Autosomal Dominant Alzheimer's Disease Colombia.

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.

Trace elements and Alzheimer dementia in population-based studies: A bibliometric and meta-analysis.

Alterations in the concentrations of trace elements may play a vital role in Alzheimer dementia progression. However, previous research results are inconsistent, and there is still a lack of review on the relationship between all the studied-trace elements and AD from various perspectives of population-based studies. In this study, we systematically reviewed previous population-based studies and identified the altered trace elements in AD patients. We searched the Web of Science Core Collection, PubMed, and Scopus database, and ultimately included 73 articles. A bibliometric analysis was conducted to explore the evolution of the field from an epidemiological perspective. Bibliometric data such as trace elements, biological materials, detection methods, cognitive tests, co-occurrence and co-citation statistics are all analyzed and presented in a quantitative manner. The 73 included studies analyzed 39 trace elements in total. In a further meta-analysis, standardized mean differences (SMDs) of 13 elements were calculated to evaluate their altered in AD patients, including copper, iron, zinc, selenium, manganese, lead, aluminum, cadmium, chromium, arsenic, mercury, cobalt, and manganese. We identified four trace elements-copper (serum), iron (plasma), zinc (hair), and selenium (plasma)-altered in AD patients, with SMDs of 0.37 (95% confidence interval [CI]: 0.10, 0.65), -0.68 (95% CI: -1.34, -0.02), -0.35 (95% CI: -0.62, -0.08), and -0.61 (95% CI: -0.97, -0.25), respectively. Finally, we formed a database of various trace element levels in AD patients and healthy controls. Our study can help future researchers gain a comprehensive understanding of the advancements in the field, and our results provide comprehensive population-based data for future research.

Effect of antioxidant intake patterns on risks of dementia and cognitive decline.

BACKGROUND: Previous studies have suggested that increased antioxidant intakes might reduce risk of cognitive disorders including Alzheimer's disease (AD). Which avenue of antioxidant intake (vitamin E/C) is more effective for decreasing risk, however, is largely unknown. OBJECTIVES: To quantitatively investigate the relationships between the pattern of antioxidant intakes and risks of dementia and cognitive decline. METHODS: We searched all related prospective cohort studies reporting antioxidant intakes (diet and/or supplement) from patients with cognitive disorders. We conducted dose-response meta-analyses to assess potential linear and non-linear dose-response relationships. Summary RRs and 95% CIs were calculated using a random- or fixed-effects model. RESULTS: 73 eligible cohort studies totaling > 28,257 participants were included in the meta-analysis; the pooled relative risks of AD were 0.75 (95% CI 0.57-0.99; I2 = 59.9%) for the dietary only intake of vitamin E, 0.73 (95% CI 0.54-1.00; I2 = 0%) for the dietary plus supplemental intake of vitamin E, and 0.70 (95% CI 0.51-0.95; I2 = 0%) for the dietary plus supplemental intake of vitamin C. Moreover, pooled RRs of AD and vitamin C intake per 20 mg/day increase were 0.98 (95% CI 0.97-0.99) via dietary plus supplemental intake, 0.98 (95% CI 0.96-1.00) in the dietary only intake and 0.98 (95% CI 0.98-0.99) in the overall intake. There were no significant associations of all-cause dementia or cognitive impairment no dementia with the antioxidant intake. CONCLUSIONS: The risk of incident AD is significantly reduced by higher consumption of vitamin C by the intake avenue of diet plus supplement.

The contemporaneous epidemic of chronic, copper deficiency.

The classical deficiency diseases have nearly disappeared from the industrialised world and are thought to be found largely in sub-Saharan Africa and South Asia. More than 80 collected medical articles, mostly from Europe and North America, describe more than 9000 people with low concentrations of copper in organs or tissues or impaired metabolic pathways dependent on copper. More than a dozen articles reveal improved anatomy, chemistry or physiology in more than 1000 patients from supplements containing copper. These criteria are diagnostic of deficiency according to The Oxford Textbook of Medicine. Alzheimer's disease, ischaemic heart disease and osteoporosis receive major emphasis here. However, impaired vision, myelodysplastic syndrome and peripheral neuropathy are mentioned. Copper deficiency probably causes some common, contemporaneous diseases. Advice is provided about opportunities for research. Seemingly authoritative statements concerning the rarity of nutritional deficiency in developed countries are wrong.

Alzheimer's Disease Association with Metals and Metalloids Concentration in Blood and Urine.

As there is some evidence that the risk for Alzheimer's disease (AD) is partially attributable to environmental exposure to some metals and metalloids, we examined an association between AD and arsenic, chromium, and selenium in 53 AD patients and 217 controls. Urinary arsenic, blood chromium, and selenium were determined by inductively coupled plasma mass spectrometry. Logistic regression models calculating odds ratios (ORs) and 95% confidence intervals (CI) were used to estimate AD association with arsenic, chromium, and selenium. In AD patients, urinary arsenic and blood chromium were significantly higher, while blood selenium was significantly lower compared to controls. Increased blood selenium was related to a significant decrease in the odds of AD after adjustment for risk factors. Blood selenium per 1 kg × 10-9/m3 × 10-4 increment was associated with 1.4 times lower risk of AD (OR = 0.71; 95% CI 0.58-0.87). A significant increase in the odds of AD associated with increased blood chromium was also seen in the adjusted model: the OR per 1 kg × 10-9/m3 × 10-3 chromium increment was 2.39 (95% CI 1.32-4.31). The association of urinary arsenic with the risk of AD was not significant. The data obtained provide evidence that selenium reduces the risk of Alzheimer's disease, while chromium increases it.

Association of Serum Antioxidant Vitamins and Carotenoids With Incident Alzheimer Disease and All-Cause Dementia Among US Adults.

BACKGROUND AND OBJECTIVES: Serum antioxidant vitamins and carotenoids may protect against neurodegeneration with age. We examined associations of these nutritional biomarkers with incident all-cause and Alzheimer disease (AD) dementia among US middle-aged and older adults. METHODS: Using data from the third National Health and Nutrition Examination Surveys (1988-1994), linked with Centers for Medicare & Medicaid follow-up data, we tested associations and interactions of serum vitamins A, C, and E and total and individual serum carotenoids and interactions with incident AD and all-cause dementia. Cox proportional hazards regression models were conducted. RESULTS: After ≤26 years follow-up (mean 16-17 years, 7,283 participants aged 45-90 years at baseline), serum lutein+zeaxanthin was associated with reduced risk of all-cause dementia (65+ age group), even in the lifestyle-adjusted model (per SD: hazard ratio [HR] 0.93, 95% CI 0.87-0.99; p = 0.037), but attenuated in comparison with a socioeconomic status (SES)-adjusted model (HR 0.92, 95% CI 0.86-0.93; p = 0.013). An inverse relationship was detected between serum ß-cryptoxanthin (per SD increase) and all-cause dementia (45+ and 65+) for age- and sex-adjusted models (HR 0.86, 95% CI 0.80-0.93; p < 0.001 for 45+; HR 0.86, 95% CI 0.80-0.93; p = 0.001 for 65+), a relationship remaining strong in SES-adjusted models (HR 0.89, 95% CI 0.82-0.96; p = 0.006 for 45+; HR 0.88, 95% CI 0.81-0.96; p = 0.007 for 65+), but attenuated in subsequent models. Antagonistic interactions indicate putative protective effects of 1 carotenoid may be observed at lower levels other carotenoids or antioxidant vitamin. DISCUSSION: Incident all-cause dementia was inversely associated with serum lutein+zeaxanthin and ß-cryptoxanthin levels. Further studies with time-dependent exposures and randomized trials are needed to test neuroprotective effects of supplementing the diet with select carotenoids. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that incident all-cause dementia was inversely associated with serum lutein+zeaxanthin and ß-cryptoxanthin levels.

Alzheimer's disease and related dementias and heart failure: A community study.

BACKGROUND: Cognitive function is essential to effective self-management of heart failure (HF). Alzheimer's disease and Alzheimer's disease-related dementias (AD/ADRD) can coexist with HF, but its exact prevalence and impact on health care utilization and death are not well defined. METHODS: Residents from 7 southeast Minnesota counties with a first-ever diagnosis code for HF between January 1, 2013 and December 31, 2018 were identified. Clinically diagnosed AD/ADRD was ascertained using the Centers for Medicare and Medicaid (CMS) Chronic Conditions Data Warehouse algorithm. Patients were followed through March 31, 2020. Cox and Andersen-Gill models were used to examine associations between AD/ADRD (before and after HF) and death and hospitalizations, respectively. RESULTS: Among 6336 patients with HF (mean age [SD] 75 years [14], 48% female), 644 (10%) carried a diagnosis of AD/ADRD at index HF diagnosis. The 3-year cumulative incidence of AD/ADRD after HF diagnosis was 17%. During follow-up (mean [SD] 3.2 [1.9] years), 2618 deaths and 15,475 hospitalizations occurred. After adjustment, patients with AD/ADRD before HF had nearly a 2.7 times increased risk of death, but no increased risk of hospitalization compared to those without AD/ADRD. When AD/ADRD was diagnosed after the index HF date, patients experienced a 3.7 times increased risk of death and a 73% increased risk of hospitalization compared to those who remain free of AD/ADRD. CONCLUSIONS: In a large, community cohort of patients with incident HF, the burden of AD/ADRD is quite high as more than one-fourth of patients with HF received a diagnosis of AD/ADRD either before or after HF diagnosis. AD/ADRD markedly increases the risk of adverse outcomes in HF underscoring the need for future studies focused on holistic approaches to improve outcomes.

Current understandings and perspectives of petroleum hydrocarbons in Alzheimer's disease and Parkinson's disease: a global concern.

Over the last few decades, the global prevalence of neurodevelopmental and neurodegenerative illnesses has risen rapidly. Although the aetiology remains unclear, evidence is mounting that exposure to persistent hydrocarbon pollutants is a substantial risk factor, predisposing a person to neurological diseases later in life. Epidemiological studies correlate environmental hydrocarbon exposure to brain disorders including neuropathies, cognitive, motor and sensory impairments; neurodevelopmental disorders like autism spectrum disorder (ASD); and neurodegenerative disorders like Alzheimer's disease (AD) and Parkinson's disease (PD). Particulate matter, benzene, toluene, ethylbenzene, xylenes, polycyclic aromatic hydrocarbons and endocrine-disrupting chemicals have all been linked to neurodevelopmental problems in all class of people. There is mounting evidence that supports the prevalence of petroleum hydrocarbon becoming neurotoxic and being involved in the pathogenesis of AD and PD. More study is needed to fully comprehend the scope of these problems in the context of unconventional oil and natural gas. This review summarises in vitro, animal and epidemiological research on the genesis of neurodegenerative disorders, highlighting evidence that supports inexorable role of hazardous hydrocarbon exposure in the pathophysiology of AD and PD. In this review, we offer a summary of the existing evidence gathered through a Medline literature search of systematic reviews and meta-analyses of the most important epidemiological studies published so far.

The health status: the ignored risk factor in dementia incidence. NEDICES cohort.

BACKGROUND: The causes of the dementia decrease in affluent countries are not well known but health amelioration could probably play a major role. Nevertheless, although many vascular and systemic disorders in adult life are well-known risk factors (RF) for dementia and Alzheimer disease (AD), health status is rarely considered as a single RF. AIM: To analyse whether the health status and the self-perceived health (SPH) could be RF for dementia and AD and to discuss its biological basis. METHODS: We analysed different objective health measures and SPH as RF for dementia and AD incidence in 4569 participants of the NEDICES cohort by means of Cox-regression models. The mean follow-up period was 3.2 (range: 0.03-6.6) years. RESULTS: Ageing, low education, history of stroke, and "poor" SPH were the main RF for dementia and AD incidence, whereas physical activity was protective. "Poor" SPH had a hazard ratio = 1.66 (95% CI 1.17-2.46; p = 0.012) after controlling for different confounders. DISCUSSION: According to data from NEDICES cohort, SPH is a better predictor of dementia and AD than other more objective health status proxies. SPH should be considered a holistic and biologically rooted indicator of health status, which can predict future development of dementia and AD in older adults. CONCLUSIONS: Our data indicate that it is worthwhile to include the SPH status as a RF in the studies of dementia and AD incidence and to explore the effect of its improvement in the evolution of this incidence.

Alzheimer's Disease: Pathogenesis and Therapeutic Interventions.

BACKGROUND: Alzheimer's Disease (AD) is the most common cause of dementia. Genetics, excessive exposure to environmental pollutants, as well as unhealthy lifestyle practices are often linked to the development of AD. No therapeutic approach has achieved complete success in treating AD; however, early detection and management with appropriate drugs are key to improving prognosis. INTERVENTIONS: The pathogenesis of AD was extensively discussed in order to understand the reasons for the interventions suggested. The interventions reviewed include the use of different therapeutic agents and approaches, gene therapy, adherence to healthy dietary plans (Mediterranean diet, Okinawan diet and MIND diet), as well as the use of medicinal plants. The potential of nanotechnology as a multidisciplinary and interdisciplinary approach in the design of nano-formulations of AD drugs and the use of Superparamagnetic Iron Oxide Nanoparticles (SPIONs) as theranostic tools for early detection of Alzheimer's disease were also discussed.

Fish intake, n-3 fatty acid body status, and risk of cognitive decline: a systematic review and a dose-response meta-analysis of observational and experimental studies.

CONTEXT: Randomized controlled trials (RCTs) testing supplementation with eicosapentaenoic (EPA) and docosahexaenoic (DHA) fatty acids have failed to provide evidence supporting a suggested inverse association between fish intake and dementia risk. OBJECTIVE: Dose-response analyses were conducted to evaluate associations between fish intake, all-cause dementia or Alzheimer's Disease (AD), and the effect of EPA/DHA supplementation on cognitive performance. DATA SOURCES: PubMed, Scopus and Web of Science databases were searched for original research evaluating either associations between fish intake and dementia or AD, or the impact of EPA and/or DHA supplementation on the risk of cognitive decline. DATA EXTRACTION: Data were collected on study characteristics and methods; number of cases/deaths (for observational studies); categories of exposure; model covariates; risk estimates from the most-adjusted model; type and dosage of supplementation (from RCTs); fatty acid levels in blood; and differences in cognition test results before and after supplementation. Risk of bias was assessed through the ROBINS-E and RoB2.0 tools for observational and experimental studies, respectively. DATA ANALYSIS: Weighted mixed-effects models were applied, allowing for the inclusion of studies with 2 levels of exposure. Based on findings with low/moderate risk of bias, fish intake of up to 2 portions (250 g) per week was associated with a 10% reduction (95% confidence interval [CI]: 0.79, 1.02, Ν = 5) in all-cause dementia and a 30% reduction (95% CI: 0.54, 0.89, Ν = 3) in AD risk. Changes in EPA and DHA body status had a positive impact on participants' executive functions, but not on their overall cognitive performance. CONCLUSION: The protection offered by fish intake against cognitive decline levels off at intakes higher than 2 portions/week and likely relates to the impact of EPA and DHA on the individual's executive functions, although there remain questions about the mechanisms linking the short- and long-term effects. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42019139528.

Low Serum Vitamin D Status Is Associated with Incident Alzheimer's Dementia in the Oldest Old.

Background. Vitamins A, D and E and beta-carotene may have a protective function for cognitive health, due to their antioxidant capacities. Methods. We analyzed data from 1334 non-demented participants (mean age 84 years) from the AgeCoDe study, a prospective multicenter-cohort of elderly general-practitioner patients in Germany, of whom n = 250 developed all-cause dementia and n = 209 developed Alzheimer's dementia (AD) during 7 years of follow-up. We examined whether concentrations of vitamins A (retinol), D (25-hydroxycholecalciferol) and E (alpha-tocopherol) and beta-carotene, would be associated with incident (AD) dementia. Results. In our sample, 33.7% had optimum vitamin D concentrations (≥50 nmol/L). Higher concentrations of vitamin D were associated with lower incidence of all-cause dementia and AD (HR 0.99 (95%CI 0.98; 0.99); HR0.99 (95%CI 0.98; 0.99), respectively). In particular, subjects with vitamin D deficiency (25.3%, <25 nmol/L) were at increased risk for all-cause dementia and AD (HR1.91 (95%CI 1.30; 2.81); HR2.28 (95%CI 1.47; 3.53), respectively). Vitamins A and E and beta-carotene were unrelated to (AD) dementia. Conclusions. Vitamin D deficiency increased the risk to develop (AD) dementia. Our study supports the advice for monitoring vitamin D status in the elderly and vitamin D supplementation in those with vitamin D deficiency. We observed no relationships between the other vitamins with incident (AD) dementia, which is in line with previous observational studies.

Alzheimer's Disease and Type 2 Diabetes Mellitus: The Use of MCT Oil and a Ketogenic Diet.

Recently, type 2 diabetes mellitus (T2DM) has been reported to be strongly associated with Alzheimer's disease (AD). This is partly due to insulin resistance in the brain. Insulin signaling and the number of insulin receptors may decline in the brain of T2DM patients, resulting in impaired synaptic formation, neuronal plasticity, and mitochondrial metabolism. In AD patients, hypometabolism of glucose in the brain is observed before the onset of symptoms. Amyloid-ß accumulation, a main pathology of AD, also relates to impaired insulin action and glucose metabolism, although ketone metabolism is not affected. Therefore, the shift from glucose metabolism to ketone metabolism may be a reasonable pathway for neuronal protection. To promote ketone metabolism, medium-chain triglyceride (MCT) oil and a ketogenic diet could be introduced as an alternative source of energy in the brain of AD patients.

Online Promotion of "Brain Health" Supplements.

Objective: To identify the dietary supplements most commonly promoted online for brain health and to compare their major ingredients over 18 months. Mild cognitive impairment and Alzheimer's disease are increasing globally with few effective treatments available. Dietary supplements are widely promoted in the media and online for brain health and memory improvement despite minimal evidence of an actual effect. Methods: Incognito mode on Google Chrome was used to conduct four separate searches using the terms: memory supplement, brain health supplement, Alzheimer's supplement, and dementia supplement. The four separate searches for products were conducted through CVS, Walgreens, Walmart, GNC, Amazon, Yahoo, and Google. For each website, the top 10 supplement products and their ingredients were documented in August 2017 and again in January 2019. Results: Of the four terms used, "memory supplement" and "brain health supplement" provided the most results. The most common products were Prevagen®, Procera®, and Neuro Health®. Amazon had the most repeated products in 2017 and 2019, while Google and CVS had the least. Focus Factor® appeared 11 times in 2019 compared with once in 2017. At both time points, the most commonly promoted products were proprietary blends of Ginkgo biloba, vitamins, particularly vitamin B12 and folic acid, huperzine-A, Bacopa monnieri, and phosphatidylserine. Conclusions: Though the 2017 and 2019 datasets showed diverse products, the primary ingredients were similar. These supplements have insufficient evidence of efficacy and are expensive. Health professionals must be knowledgeable about dietary supplements for brain health to appropriately counsel individuals.

Patterns of incident dementia codes during the COVID-19 pandemic at an integrated healthcare system.

BACKGROUND: The COVID-19 pandemic delayed diagnosis and care for some acute conditions and reduced monitoring for some chronic conditions. It is unclear whether new diagnoses of chronic conditions such as dementia were also affected. We compared the pattern of incident Alzheimer's disease and related dementia (ADRD) diagnosis codes from 2017 to 2019 through 2020, the first pandemic year. METHODS: Retrospective cohort design, leveraging 2015-2020 data on all members 65 years and older with no prior ADRD diagnosis, enrolled in a large integrated healthcare system for at least 2 years. Incident ADRD was defined as the first ICD-10 code at any encounter, including outpatient (face-to-face, video, or phone), hospital (emergency department, observation, or inpatient), or continuing care (home, skilled nursing facility, and long-term care). We also examined incident ADRD codes and use of telehealth by age, sex, race/ethnicity, and spoken language. RESULTS: Compared to overall annual incidence rates for ADRD codes in 2017-2019, 2020 incidence was slightly lower (1.30% vs. 1.40%), partially compensating later in the year for reduced rates during the early months of the pandemic. No racial or ethnic group differences were identified. Telehealth ADRD codes increased fourfold, making up for a 39% drop from face-to-face outpatient encounters. Older age (85+) was associated with higher odds of receiving telecare versus face-to-face care in 2020 (OR:1.50, 95%CI: 1.25-1.80) and a slightly lower incidence of new codes; no racial/ethnic, sex, or language differences were identified in the mode of care. CONCLUSIONS: Rates of incident ADRD codes dropped early in the first pandemic year but rose again to near pre-pandemic rates for the year as a whole, as clinicians rapidly pivoted to telehealth. With refinement of protocols for remote dementia detection and diagnosis, health systems could improve access to equitable detection and diagnosis of ADRD going forward.

Genetically Predicted Coffee Consumption and Risk of Alzheimer's Disease and Stroke.

BACKGROUND: Observational studies have reported that coffee consumption was associated with Alzheimer's disease (AD) and stroke risk. However, the results are inconclusive. OBJECTIVE: We aimed to evaluate whether genetically predicted coffee consumption is associated with AD and stroke using Mendelian randomization (MR) design. METHODS: Summary-level data for AD (n = 54,162), ischemic stroke (n = 440,328), and intracerebral hemorrhage (ICH, n = 3,026) were adopted from publicly available databases. Summary-level data for coffee consumption were obtained from two genome-wide association studies, comprising up to 375,833 subjects. RESULTS: Genetically predicted coffee consumption (cups/day) was associated with an increased risk of AD (OR = 1.26, 95%CI = 1.05-1.51). Moreover, genetically predicted 50%increase of coffee consumption was associated with an increased risk of ICH (OR: 2.27, 95%CI: 1.08-4.78) but a decreased risk of small vessel stroke (OR: 0.71, 95%CI: 0.51-0.996). Estimate for AD and ICH in FinnGen consortium is directionally consistent. Combined analysis of different databases further confirmed that genetically predicted coffee consumption was associated with an increased risk of AD and ICH. In the multivariable MR analysis, genetically predicted coffee consumption retained a stable effect with AD and ICH when adjusting for smoking (p < 0.05), while the association with AD attenuated when adjusting for alcohol use. CONCLUSION: Our results indicate that genetically predicted coffee consumption may be associated with an increased risk of AD and ICH. The underlying biological mechanisms warrant further study.