Analysis of human ABO Blood Group as a risk factor with knee osteoarthritis at tertiary care hospital in Pakistan.

Objective: To investigate the association and risk estimation of ABO blood group distribution and clinical attributes in patients with Knee Osteoarthritis. Method: This was a hospital-based study conducted at, Liaquat University Hospital Hyderabad from December, 2019 to December, 2022 to investigate this least researched area of highly prevalent musculoskeletal disease in Pakistan. Non-Probability Convenience Sampling was used for selecting 190 cases of confirm Knee Osteoarthritis patients diagnosed by Orthopedic surgeon based on standard clinical and radiographic criteria. Data were analyzed using IBM-SPSS version 23.0. Percentages and frequencies were counted for categorical data. Pearson Chi Square test and fisher's exact test were used to check the association and Multinomial Logistic Regression was used to estimate the risk for moderate and severe kellgren grading Knee Osteoarthritis (KOA) cases with ABO blood grouping in comparison of mild Kellgren grading. Results: A total of 190 cases of Knee Osteoarthritis (KOA) were included in the study. Females (61.6%) and patients with age 50 and above were 40.5 % were found in greater proportion. Majority (41.6%) were classified radiologically as mild cases with O group (39.5%) and positive Rh antigen (95.8%). Strong association (p = <0.01) was found between gender, age group and ABO blood group with KOA radiological Kellgren and Lawrence score. Conclusion: There is strong relation in between radiological grading of knee osteoarthritis severity and A blood group, gender and age.

Evaluating the Oral-Health-Related Quality of Life of Oral Submucous Fibrosis Patients before and after Treatment Using the OHIP-14 Tool.

The objective of the present study was to assess the oral-health-related quality of life (OHRQoL) of oral submucous fibrosis (OSMF) patients before and after standard treatment. A convenient sampling technique was used to recruit the clinically diagnosed patients of OSMF (n = 130). Based on the medical treatment, the patients were randomly divided into two study groups (group A and B). The group A patients received submucosal intralesional injections of dexamethasone (2 mL; 4 gm/mL), while group B patients received hyaluronidase (1500 IU). Both the group A and B patients received respective medical therapy biweekly for a period of five weeks. At the follow up visit (6 months), the impact of treatment on OHRQoL was assessed using the Oral Health Impact Profile-14 (OHIP-14). Data were analyzed by a chi-square test for quantitative variables and an independent t-test for qualitative variables. The comparison of all clinical parameters before and after treatment was performed by a paired t-test. The results after treatment showed that there was a significant improvement in all domains of OHIP-14 (p = 0.001) except psychological disability (p = 0.243). In addition, the OHRQoL of patients was significantly improved following the treatment.

Purification and extraction of fibroblast growth factor 21 (FGF-21) protein by sumo fusion in Escherichia coli.

Fibroblast growth factor 21 has recently discovered its pivotal role in glucose, lipid metabolism and regulation of energy homeostasis. Further, it has helped in forming great strides for treatment of chronic diseases like diabetes and inflammation. FGF-21 was sub-cloned into the SUMO vector and was induced for expression in Escherichia coli Rosetta. The recombinant plasmid was transformed into Escherichia coli strain. FGF-21 was induced by IPTG and purified by Ni-NTA agarose (Nickel-nitrilotriacetic acid) column. The purified fusion protein was cleavaged by SUMO protease I to obtain recombinant FGF-21 with high purity. The purified protein was tested for its biological activity of FGF-21. HepG2 cell model was used to detect the regulation of glucose uptake activity of FGF-21 and were further treated with different concentrations of FGF-21.The residual glucose content in medium was measured using the glucose oxidase-peroxidase method. The results indicated that FGF-21 protein had a role in regulating the glucose uptake on HepG2 cells and the effect was significantly dose-dependent manner. In order to further verify whether purified FGF-21 protein obtained has biological activity in diabetic model. Studies have demonstrated that FGF-21 had a greater efficacy in dropping blood glucose in streptozotocin induced diabetic mice.

An Investigation of Selected Socio-Demographic Factors with Aplastic Anemia in Pakistan: A Case-Control Study.

INTRODUCTION: In Pakistan, the incidence rate of aplastic anemia is 3.5 cases/million. The associated risk factors are exposure to pesticides, chemicals, and some drugs. The link between aplastic anemia and socio-demographic factors is debatable. PURPOSE: We conducted this study to investigate the role of socio-economic and -demographic factors with aplastic anemia. METHODOLOGY: A total of 191 lab-confirmed incident cases of aplastic anemia were identified from the tertiary hospital of Karachi-Pakistan in between 2015 and 2018. Age and gender-matched 694 controls were randomly selected from the same institute admitted or visited for other non-neoplastic conditions. Socio-demographic and exposure information was gathered using a data collection form. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were computed for selected socio-demographic factors. RESULTS: Among socio-demographic factors, significant associations of aplastic anemia risk emerged for illiteracy (aOR: 2.3; 1.5; 3.5) occupation (any type) (aOR: 2.1; 1.7; 2.5), living in rural environments (aOR: 2.9; 1.9; 4.2). The odds of aplastic anemia increased with the age group 31-50 years (aOR: 1.8; 1.7; 3.5) and >50 years (aOR: 2.5; 2.1; 4.2). We observed no association of income with the risk of aplastic anemia. CONCLUSION: This study highlights the importance of socio-demographic factors as a risk factor for the development of aplastic anemia in the population of Pakistan. In order to reduce disease incidence, health education program and use of personal protective equipment and organization of screening camps in high-risk population is warranted.

Assessing the Quality of Life of Oral Submucous Fibrosis Patients: A Cross-Sectional Study Using the WHOQOL-BREF Tool.

The aim of the present study was to evaluate the quality of life (QoL) of oral submucous fibrosis (OSMF) patients using the World Health Organization Quality of Life-BREF (WHOQOL-BREF) questionnaire. This cross-sectional study was conducted at the Department of Oral and Maxillofacial Surgery, Liaquat University of Medical and Health Sciences (LUMHS), Jamshoro. We used the consecutive sampling technique to recruit patients who were clinically diagnosed with OSMF (n = 112). Data were collected using the WHOQOL-BREF questionnaire, which contains a total of 26 questions. The first two questions, related to overall QoL and overall health status, were evaluated separately. The remaining questions (3-26), which represented four domains-physical, psychological, social, and environmental health-were evaluated separately. Patients were asked questions in their native language (Urdu). The relationship between these four domains of life was evaluated with gender, age categories, functional staging, and habit duration using the independent t-test to determine statistical significance. Cronbach's Alpha was used to assess the reliability of the WHOQOL-BREF domains. The overall QoL of the OSMF patients was considerably poor, and the majority of the patients were unsatisfied with their oral health status. The age variable significantly affected the scores of all domains except for social relationships, whereas habit duration and functional staging of OSMF did not significantly affect the scores of all domains. The domains of the WHOQOL-BREF questionnaire (translated into the Urdu language) showed good reliability, except for social relationships.

The Relationship of Drug Therapy to Aplastic Anemia in Pakistan: A Hospital-Based Case Control Study.

INTRODUCTION: Drug-induced aplastic anemia has long been a menacing outcome of modern pharmacotherapy. The incidence of idiosyncratic, drug-induced aplastic anemia varies depending on the genetic susceptibility and the associated drug. Only scarce studies have explained the epidemiology and actual incidence of this reaction. PURPOSE: The aim of the study was to establish the association between drugs and aplastic anemia. METHODS: A case-control study was conducted with 191 cases and 696 controls at a tertiary hospital for blood diseases in Karachi-Pakistan. Cases were patients of aplastic anemia diagnosed through bone marrow biopsy. The controls did not have either AA or chronic diseases. Each case was paired with four sex and age group match controls. Cases and controls were compared with respect to the drugs used. Univariate and multivariate analysis were performed in order to delineate the association. RESULTS: Median age of the study-participants was 27 years (04-69 years). The majority 84 (44%) were from age group 16 to 30 years. The male-to-female ratio was 2:1. Among study participants, various drugs were significantly associated with aplastic anemia. Treatment of epilepsy with carbamazepine showed a positive association (OR=2.7, 95% C.I, 1.0-6.8). An increased risk of aplastic anemia was noted with exposure to thiazide (OR=3.1, 95% C.I, 1.3-7.4) and mebendazole (OR=3.7, 95% C.I, 1.5-9.2). However, risks were not increased with chloramphenicol, trimethoprim/sulfamethoxazole, benzodiazepines, antihistamines, oral contraceptives, and herbal medicine. CONCLUSION: This large-scale case-control study provide association of aplastic anemia with exposure to carbamazepine, thiazides and mebendazole in population of Pakistan. Patients should be monitored with complete blood indices for early detection of drug toxicity.

Evaluation of C-reactive protein and hematological parameters in smokeless tobacco users: A comparative cross-sectional study.

OBJECTIVE: To investigate the changes in levels of C-reactive protein (CRP) and hematological parameters among smokeless tobacco (SLT) users. METHODS: A comparative cross-sectional study was conducted at the community level in the coastal districts of Sindh province namely Badin, Thatta, and Sujawal from January 2017 to December 2019. The CRP and hematological parameters were evaluated by well-established methods among SLT and non-SLT users. RESULTS: There was a statistically significant difference between SLT users (mean CRP = 0.77) versus non-users (mean CRP = 0.18), p = <0.001. Among hematological parameters, white blood cells (SLT users median = 7.85 versus non-SLT users median = 8.50, p = 0.004), monocytes (SLT users median = 6.00 versus non-SLT users median = 6.00, p = 0.001) and erythrocyte sedimentation rate (SLT users median = 15.00 versus non-SLT users median = 10.00, p = 0.006) showed statistically significant difference. CONCLUSIONS: Significantly elevated CRP was observed in SLT users similarly hematological parameters also showed changes. WBCs, monocytes and ESR were significantly deranged among SLT users. Further studies looking into long term effects of these changes would be helpful.

Pesticides and Chemicals as Potential Risk Factors of Aplastic Anemia: A Case-Control Study Among a Pakistani Population.

INTRODUCTION: Aplastic anemia is a rare and potentially life-threatening hematological disorder with incidence of 1.4 to 14 cases/million. It is associated with exposures to certain environmental chemicals, drugs and infections. The objective was to investigate the association of illness with family history of aplastic anemia, exposure to pesticides and chemicals. METHODOLOGY: A hospital-based case-control study (191 cases, 696 controls) was conducted from 1st January 2015 to 31st December 2018 in Karachi, Sindh. Cases were patients with diagnosis of aplastic anemia confirmed with bone marrow biopsy. Controls neither had aplastic anemia nor other hematological chronic diseases. An in-person interview was conducted to collect demographic information, family history of aplastic anemia, and history of pesticide and chemical exposure. The adjusted odds ratios (aOR) with 95% confidence intervals (CI) were estimated via SPSS v22. RESULTS: A total of 191 confirmed aplastic anemia cases were selected. Mean age was 29 years (range: 4-69) and predominantly there were males 129 (67.5%). The majority, 84 (44.0%), of the cases were aged 16-30 years. In multivariate analysis models, the significant associations were observed between aplastic anemia with family history of aplastic anemia (aOR=13.3, 95% C.I 3.66-48.50), exposure to pesticides (aOR=2.1, 95% C.I 1.23-3.61) and chemicals (aOR=3.6, 95% C.I 2.06-6.34). CONCLUSION: This study observed a significant association of aplastic anemia with family history of aplastic anemia, exposure to pesticide and insecticide exposure. However, to establish this connection, further longitudinal studies are warranted.

Menopause impacts human brain structure, connectivity, energy metabolism, and amyloid-beta deposition.

All women undergo the menopause transition (MT), a neuro-endocrinological process that impacts aging trajectories of multiple organ systems including brain. The MT occurs over time and is characterized by clinically defined stages with specific neurological symptoms. Yet, little is known of how this process impacts the human brain. This multi-modality neuroimaging study indicates substantial differences in brain structure, connectivity, and energy metabolism across MT stages (pre-menopause, peri-menopause, and post-menopause). These effects involved brain regions subserving higher-order cognitive processes and were specific to menopausal endocrine aging rather than chronological aging, as determined by comparison to age-matched males. Brain biomarkers largely stabilized post-menopause, and gray matter volume (GMV) recovered in key brain regions for cognitive aging. Notably, GMV recovery and in vivo brain mitochondria ATP production correlated with preservation of cognitive performance post-menopause, suggesting adaptive compensatory processes. In parallel to the adaptive process, amyloid-ß deposition was more pronounced in peri-menopausal and post-menopausal women carrying apolipoprotein E-4 (APOE-4) genotype, the major genetic risk factor for late-onset Alzheimer's disease, relative to genotype-matched males. These data show that human menopause is a dynamic neurological transition that significantly impacts brain structure, connectivity, and metabolic profile during midlife endocrine aging of the female brain.

Relationship of self-reported body size and shape with risk for prostate cancer: A UK case-control study.

INTRODUCTION: Previous evidence has suggested a relationship between male self-reported body size and the risk of developing prostate cancer. In this UK-wide case-control study, we have explored the possible association of prostate cancer risk with male self-reported body size. We also investigated body shape as a surrogate marker for fat deposition around the body. As obesity and excessive adiposity have been linked with increased risk for developing a number of different cancers, further investigation of self-reported body size and shape and their potential relationship with prostate cancer was considered to be appropriate. OBJECTIVE: The study objective was to investigate whether underlying associations exist between prostate cancer risk and male self-reported body size and shape. METHODS: Data were collected from a large case-control study of men (1928 cases and 2043 controls) using self-administered questionnaires. Data from self-reported pictograms of perceived body size relating to three decades of life (20's, 30's and 40's) were recorded and analysed, including the pattern of change. The associations of self-identified body shape with prostate cancer risk were also explored. RESULTS: Self-reported body size for men in their 20's, 30's and 40's did not appear to be associated with prostate cancer risk. More than half of the subjects reported an increase in self-reported body size throughout these three decades of life. Furthermore, no association was observed between self-reported body size changes and prostate cancer risk. Using 'symmetrical' body shape as a reference group, subjects with an 'apple' shape showed a significant 27% reduction in risk (Odds ratio = 0.73, 95% C.I. 0.57-0.92). CONCLUSIONS: Change in self-reported body size throughout early to mid-adulthood in males is not a significant risk factor for the development of prostate cancer. Body shape indicative of body fat distribution suggested that an 'apple' body shape was protective and inversely associated with prostate cancer risk when compared with 'symmetrical' shape. Further studies which investigate prostate cancer risk and possible relationships with genetic factors known to influence body shape may shed further light on any underlying associations.

Sex-driven modifiers of Alzheimer risk: A multimodality brain imaging study.

OBJECTIVE: To investigate sex differences in late-onset Alzheimer disease (AD) risks by means of multimodality brain biomarkers (ß-amyloid load via 11C-Pittsburgh compound B [PiB] PET, neurodegeneration via 18F-fluorodeoxyglucose [FDG] PET and structural MRI). METHODS: We examined 121 cognitively normal participants (85 women and 36 men) 40 to 65 years of age with clinical, laboratory, neuropsychological, lifestyle, MRI, FDG- and PiB-PET examinations. Several clinical (e.g., age, education, APOE status, family history), medical (e.g., depression, diabetes mellitus, hyperlipidemia), hormonal (e.g., thyroid disease, menopause), and lifestyle AD risk factors (e.g., smoking, diet, exercise, intellectual activity) were assessed. Statistical parametric mapping and least absolute shrinkage and selection operator regressions were used to compare AD biomarkers between men and women and to identify the risk factors associated with sex-related differences. RESULTS: Groups were comparable on clinical and cognitive measures. After adjustment for each modality-specific confounders, the female group showed higher PiB ß-amyloid deposition, lower FDG glucose metabolism, and lower MRI gray and white matter volumes compared to the male group (p < 0.05, family-wise error corrected for multiple comparisons). The male group did not show biomarker abnormalities compared to the female group. Results were independent of age and remained significant with the use of age-matched groups. Second to female sex, menopausal status was the predictor most consistently and strongly associated with the observed brain biomarker differences, followed by hormone therapy, hysterectomy status, and thyroid disease. CONCLUSION: Hormonal risk factors, in particular menopause, predict AD endophenotype in middle-aged women. These findings suggest that the window of opportunity for AD preventive interventions in women is early in the endocrine aging process.

Effectiveness of online education for recruitment to an Alzheimer's disease prevention clinical trial.

INTRODUCTION: Low awareness of Alzheimer's disease (AD) clinical trials is a recruitment barrier. To assess whether online education may affect screening rates for AD prevention clinical trials, we conducted an initial prospective cohort study (n = 10,450) and subsequent randomized study (n = 351) using an online digital tool: AlzU.org. METHODS: A total of 10,450 participants were enrolled in an initial cohort study and asked to complete a six-lesson course on AlzU.org, as well as a baseline and 6-month follow-up questionnaire. Participants were stratified into three groups based on lesson completion at 6 months: group 1 (zero to one lesson completed), group 2 (two to four lessons), and group 3 (five or more lessons). For the subsequent randomized-controlled trial (RCT), 351 new participants were enrolled in a six-lesson course (n = 180) versus a time-neutral control (n = 171). Screening and enrollment in the Anti-Amyloid Treatment in Asymptomatic AD (A4) clinical trial were reported via the 6-month questionnaire and are the primary outcomes. RESULTS: Cohort: 3.9% of group 1, 5% of group 2, and 8.4% of group 3 screened for the A4 trial. Significant differences were found among the groups (P < 0.001). Post hoc analyses showed differences in A4 screening rates between groups 1 and 3 (P < 0.001) and groups 2 and 3 (P = 0.0194). There were no differences in enrollment among the three groups. RCT: 2.78% of the intervention group screened for A4 compared to 0% of controls (P = 0.0611). DISCUSSION: Online education via the AlzU.org digital tool may serve as an effective strategy to supplement clinical trial recruitment.

Sex and Gender Driven Modifiers of Alzheimer's: The Role for Estrogenic Control Across Age, Race, Medical, and Lifestyle Risks.

Research indicates that after advanced age, the major risk factor for late-onset Alzheimer's disease (AD) is female sex. Out of every three AD patients, two are females with postmenopausal women contributing to over 60% of all those affected. Sex- and gender-related differences in AD have been widely researched and several emerging lines of evidence point to different vulnerabilities that contribute to dementia risk. Among those being considered, it is becoming widely accepted that gonadal steroids contribute to the gender disparity in AD, as evidenced by the "estrogen hypothesis." This posits that sex hormones, 17ß-estradiol in particular, exert a neuroprotective effect by shielding females' brains from disease development. This theory is further supported by recent findings that the onset of menopause is associated with the emergence of AD-related brain changes in women in contrast to men of the same age. In this review, we discuss genetic, medical, societal, and lifestyle risk factors known to increase AD risk differently between the genders, with a focus on the role of hormonal changes, particularly declines in 17ß-estradiol during the menopause transition (MT) as key underlying mechanisms.

Individualized clinical management of patients at risk for Alzheimer's dementia.

INTRODUCTION: Multidomain intervention for Alzheimer's disease (AD) risk reduction is an emerging therapeutic paradigm. METHODS: Patients were prescribed individually tailored interventions (education/pharmacologic/nonpharmacologic) and rated on compliance. Normal cognition/subjective cognitive decline/preclinical AD was classified as Prevention. Mild cognitive impairment due to AD/mild-AD was classified as Early Treatment. Change from baseline to 18 months on the modified Alzheimer's Prevention Cognitive Composite (primary outcome) was compared against matched historical control cohorts. Cognitive aging composite (CogAging), AD/cardiovascular risk scales, and serum biomarkers were secondary outcomes. RESULTS: One hundred seventy-four were assigned interventions (age 25-86). Higher-compliance Prevention improved more than both historical cohorts (P = .0012, P < .0001). Lower-compliance Prevention also improved more than both historical cohorts (P = .0088, P < .0055). Higher-compliance Early Treatment improved more than lower compliance (P = .0007). Higher-compliance Early Treatment improved more than historical cohorts (P < .0001, P = .0428). Lower-compliance Early Treatment did not differ (P = .9820, P = .1115). Similar effects occurred for CogAging. AD/cardiovascular risk scales and serum biomarkers improved. DISCUSSION: Individualized multidomain interventions may improve cognition and reduce AD/cardiovascular risk scores in patients at-risk for AD dementia.

Utility of the NIH Toolbox for assessment of prodromal Alzheimer's disease and dementia.

INTRODUCTION: The NIH Toolbox Cognition Battery (NIHTB-CB) is a computer-based protocol not yet validated for clinical assessment. METHODS: We administered the NIHTB-CB and traditional neuropsychological tests to 247 Memory Disorders and Alzheimer's Prevention Clinic patients with subjective cognitive decline, mild cognitive impairment, mild dementia due to Alzheimer's disease, and normal cognition. Principal component analysis, partial correlations, and univariate general linear model tests were performed to assess construct validity. Discriminant function analyses compared classification accuracy. RESULTS: Principal component analysis identified three conceptually coherent factors: memory (MEMNIH), executive function (EFNIH), and crystallized intelligence (CINIH). These factors were strongly associated with corresponding traditional tests and differed across diagnostic groups as expected. Both NIHTB and traditional batteries yielded strong overall discriminative ability (>80%). DISCUSSION: The NIHTB-CB is a valid method to assess neurocognitive domains pertinent to aging and dementia and has utility for applications in a memory clinic setting.

Increased Alzheimer's risk during the menopause transition: A 3-year longitudinal brain imaging study.

Two thirds of all persons with late-onset Alzheimer's disease (AD) are women. Identification of sex-based molecular mechanisms underpinning the female-based prevalence of AD would advance development of therapeutic targets during the prodromal AD phase when prevention or delay in progression is most likely to be effective. This 3-year brain imaging study examines the impact of the menopausal transition on Alzheimer's disease (AD) biomarker changes [brain ß-amyloid load via 11C-PiB PET, and neurodegeneration via 18F-FDG PET and structural MRI] and cognitive performance in midlife. Fifty-nine 40-60 year-old cognitively normal participants with clinical, neuropsychological, and brain imaging exams at least 2 years apart were examined. These included 41 women [15 premenopausal controls (PRE), 14 perimenopausal (PERI), and 12 postmenopausal women (MENO)] and 18 men. We used targeted minimum loss-based estimation to evaluate AD biomarker and cognitive changes. Older age was associated with baseline Aß and neurodegeneration markers, but not with rates of change in these biomarkers. APOE4 status influenced change in Aß load, but not neurodegenerative changes. Longitudinally, MENO and PERI groups showed declines in estrogen-dependent memory tests as compared to men (p < .04). Adjusting for age, APOE4 status, and vascular risk confounds, the MENO and PERI groups exhibited higher rates of CMRglc decline as compared to males (p ≤ .015). The MENO group exhibited the highest rate of hippocampal volume loss (p's ≤ .001), and higher rates of Aß deposition than males (p < .01). CMRglc decline exceeded Aß and atrophy changes in all female groups vs. men. These findings indicate emergence and progression of a female-specific hypometabolic AD-endophenotype during the menopausal transition. These findings suggest that the optimal window of opportunity for therapeutic intervention to prevent or delay progression of AD endophenotype in women is early in the endocrine aging process.

The clinical practice of risk reduction for Alzheimer's disease: A precision medicine approach.

Like virtually all age-related chronic diseases, late-onset Alzheimer's disease (AD) develops over an extended preclinical period and is associated with modifiable lifestyle and environmental factors. We hypothesize that multimodal interventions that address many risk factors simultaneously and are individually tailored to patients may help reduce AD risk. We describe a novel clinical methodology used to evaluate and treat patients at two Alzheimer's Prevention Clinics. The framework applies evidence-based principles of clinical precision medicine to tailor individualized recommendations, follow patients longitudinally to continually refine the interventions, and evaluate N-of-1 effectiveness (trial registered at ClinicalTrials.gov NCT03687710). Prior preliminary results suggest that the clinical practice of AD risk reduction is feasible, with measurable improvements in cognition and biomarkers of AD risk. We propose using these early findings as a foundation to evaluate the comparative effectiveness of personalized risk management within an international network of clinician researchers in a cohort study possibly leading to a randomized controlled trial.

Precision Medicine for Alzheimer's Disease Prevention.

Precision medicine is an approach to medical treatment and prevention that takes into account individual variability in genes, environment, and lifestyle and allows for personalization that is based on factors that may affect the response to treatment. Several genetic and epigenetic risk factors have been shown to increase susceptibility to late-onset Alzheimer's disease (AD). As such, it may be beneficial to integrate genetic risk factors into the AD prevention approach, which in the past has primarily been focused on universal risk-reduction strategies for the general population rather than individualized interventions in a targeted fashion. This review discusses examples of a "one-size-fits-all" versus clinical precision medicine AD prevention strategy, in which the precision medicine approach considers two genes that can be commercially sequenced for polymorphisms associated with AD, apolipoprotein E (APOE), and methylenetetrahydrofolate reductase (MTHFR). Comparing these two distinct approaches provides support for a clinical precision medicine prevention strategy, which may ultimately lead to more favorable patient outcomes as the interventions are targeted to address individualized risks.

Mechanisms of Risk Reduction in the Clinical Practice of Alzheimer's Disease Prevention.

Alzheimer's disease (AD) is a neurodegenerative dementia that affects nearly 50 million people worldwide and is a major source of morbidity, mortality, and healthcare expenditure. While there have been many attempts to develop disease-modifying therapies for late-onset AD, none have so far shown efficacy in humans. However, the long latency between the initial neuronal changes and onset of symptoms, the ability to identify patients at risk based on family history and genetic markers, and the emergence of AD biomarkers for preclinical disease suggests that early risk-reducing interventions may be able to decrease the incidence of, delay or prevent AD. In this review, we discuss six mechanisms-dysregulation of glucose metabolism, inflammation, oxidative stress, trophic factor release, amyloid burden, and calcium toxicity-involved in AD pathogenesis that offer promising targets for risk-reducing interventions. In addition, we offer a blueprint for a multi-modality AD risk reduction program that can be clinically implemented with the current state of knowledge. Focused risk reduction aimed at particular pathological factors may transform AD to a preventable disorder in select cases.

Alzheimer's "Prevention" vs. "Risk Reduction": Transcending Semantics for Clinical Practice.

The terms "prevention" and "risk reduction" are often used interchangeably in medicine. There is considerable debate, however, over the use of these terms in describing interventions that aim to preserve cognitive health and/or delay disease progression of Alzheimer's disease (AD) for patients seeking clinical care. Furthermore, it is important to distinguish between Alzheimer's disease prevention and Alzheimer's dementia prevention when using these terms. While prior studies have codified research-based criteria for the progressive stages of AD, there are no clear clinical consensus criteria to guide the use of these terms for physicians in practice. A clear understanding of the implications of each term will help guide clinical practice and clinical research. The authors explore the semantics and appropriate use of the terms "prevention" and "risk reduction" as they relate to AD in clinical practice.