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The secreted peptide adropin is highly expressed in human brain tissues and correlates with RNA and proteomic risk indicators for dementia. Here we report that plasma adropin concentrations predict risk for cognitive decline in the Multidomain Alzheimer Preventive Trial (ClinicalTrials.gov Identifier, NCT00672685; mean age 75.8y, SD = 4.5 years, 60.2% female, n = 452). Cognitive ability was evaluated using a composite cognitive score (CCS) that assessed four domains: memory, language, executive function, and orientation. Relationships between plasma adropin concentrations and changes in CCS (∆CCS) were examined using Cox Proportional Hazards Regression, or by grouping into tertiles ranked low to high by adropin values and controlling for age, time between baseline and final visits, baseline CCS, and other risk factors (e.g., education, medication, APOE4 status). Risk of cognitive decline (defined as a ∆CCS of − 0.3 or more) decreased with increasing plasma adropin concentrations (hazard ratio = 0.873, 95% CI 0.780–0.977, P = 0.018). Between adropin tertiles, ∆CCS was significantly different (P = 0.01; estimated marginal mean ± SE for the 1st to 3rd tertile, − 0.317 ± 0.064; − 0.275 ± 0.063; − 0.042 ± 0.071; n = 133,146, and 130, respectively; P < 0.05 for 1st vs. 2nd and 3rd adropin tertiles). Normalized plasma Aß42/40 ratio and plasma neurofilament light chain, indicators of neurodegeneration, were significantly different between adropin tertile. These differences were consistent with reduced risk of cognitive decline with higher plasma adropin levels. Overall, these results suggest cognitive decline is reduced in community-dwelling older adults with higher circulating adropin levels. Further studies are needed to determine the underlying causes of the relationship and whether increasing adropin levels can delay cognitive decline. [ABSTRACT FROM AUTHOR]

Background: Prescribing benzodiazepines to older patients is controversial. Anxiety disorders and benzodiazepines have been associated with dementia, but literature is inconsistent. It is unknown if anxiety treated with a benzodiazepine, compared to anxiety disorder alone is associated with dementia risk. Methods: A retrospective cohort study (n = 72,496) was conducted using electronic health data from 2014 to 2021. Entropy balancing controlled for bias by indication and other confounding factors. Participants: Eligible patients were ≥65 years old, had clinic encounters before and after index date and were free of dementia for 2 years prior to index date. Of the 72,496 eligible patients, 85.6% were White and 59.9% were female. Mean age was 74.1 (SD ± 7.1) years. Exposure: Anxiety disorder was a composite of generalized anxiety disorder, anxiety not otherwise specified, panic disorder, and social phobia. Sustained benzodiazepine use was defined as at least two separate prescription orders in any 6‐month period. Main outcome and measures: ICD‐9 or ICD‐10 dementia diagnoses. Results: Six percent of eligible patients had an anxiety diagnosis and 3.6% received sustained benzodiazepine prescriptions. There were 6640 (9.2%) incident dementia events. After controlling for confounders, both sustained benzodiazepine use (HR 1.28, 95% CI: 1.11–1.47) and a diagnosis of anxiety (HR 1.19, 95% CI: 1.06–1.33) were associated with incident dementia in patients aged 65–75. Anxiety disorder with sustained benzodiazepine, compared to anxiety disorder alone, was not associated with incident dementia (HR 1.18, 95% CI: 0.92–1.51) after controlling for confounding. Results were not significant when limiting the sample to those ≥75 years of age. Conclusions: Benzodiazepines and anxiety disorders are associated with increased risk for dementia. In patients with anxiety disorders, benzodiazepines were not associated with additional dementia risk. Further research is warranted to determine if benzodiazepines are associated with a reduced or increased risk for dementia compared to other anxiolytic medications in patients with anxiety disorders. [ABSTRACT FROM AUTHOR]

An editorial is presented which explores the potential link between routine vaccinations (e.g., influenza vaccines) and reduced risk of dementia, based on emerging evidence of the role of the immune system and inflammation in dementia pathogenesis and various studies suggesting a protective link between some routinely used vaccines and dementia. The authors use the Bradford-Hill criteria, an epidemiological approach.

There is growing evidence that cognitive decline can be affected by both nutritional aspects and inflammation. Plasma neurodegenerative biomarkers stand out as minimally invasive useful measures to monitor the potential risk of cognitive decline. This study aimed to investigate the associations between biomarkers of neurodegeneration, nutrition, and inflammation among community-dwelling older adults, and to verify if associations differed according to apolipoprotein E (APOE) ε4 status. This cross-sectional analysis included 475 participants ≥70 years old from the Multidomain Alzheimer Preventive Trial (MAPT), mean age 76.8 years (SD = 4.5), 59.4% women. Biomarkers of neurodegeneration (plasma amyloid-β 42/40—Aβ 42/40, neurofilament light chain—NfL, progranulin), nutrition (erythrocyte docosahexaenoic acid, eicosapentaenoic acid, omega-3 index; plasma homocysteine—Hcy, 25 hydroxyvitamin D), inflammation (plasma tumor necrosis factor receptor 1—TNFR-1, monocyte chemoattractant protein 1—MCP-1, interleukin 6—IL-6), and cellular stress (plasma growth differentiation factor 15—GDF-15) were assessed. Linear regression analyses were performed to investigate the associations between nutritional and inflammatory biomarkers (independent variables) and neurodegenerative biomarkers (dependent variables), with adjustments for age, sex, education, body mass index, physical activity, allocation to MAPT groups, and APOE ε4 status. After adjusting for confounders, Aβ 42/40 was not associated with nutritional or inflammatory markers. NfL was positively associated with GDF-15, TNFR-1, IL-6, and Hcy. Progranulin was positively associated with GDF-15, TNFR-1, and MCP-1. Analyses restricted to APOE ε4 carriers (n = 116; 26.9%) or noncarriers were mostly similar. Our cross-sectional study with community-dwelling older adults corroborates previous evidence that inflammatory pathways are associated to plasma markers of neurodegeneration. Clinical Trials Registration Number: NCT00672685 [ABSTRACT FROM AUTHOR]

The etiology for late-onset Alzheimer's disease (LOAD), which accounts for >95% of Alzheimer's disease (AD) cases, is unknown. Emerging evidence suggests that cellular senescence contributes importantly to AD pathophysiology, although the mechanisms underlying brain cell senescence and by which senescent cells promote neuro-pathophysiology remain unclear. In this study we show for the first time that the expression of plasminogen activator inhibitor 1 (PAI-1), a serine protease inhibitor, is increased, in correlation with the increased expression of cell cycle repressors p53 and p21, in the hippocampus/cortex of senescence accelerated mouse prone 8 (SAMP8) mice and LOAD patients. Double immunostaining results show that astrocytes in the brain of LOAD patients and SAMP8 mice express higher levels of senescent markers and PAI-1, compared to astrocytes in the corresponding controls. In vitro studies further show that overexpression of PAI-1 alone, intracellularly or extracellularly, induced senescence, whereas inhibition or silencing PAI-1 attenuated H2O2-induced senescence, in primary mouse and human astrocytes. Treatment with the conditional medium (CM) from senescent astrocytes induced neuron apoptosis. Importantly, the PAI-1 deficient CM from senescent astrocytes that overexpress a secretion deficient PAI-1 (sdPAI-1) has significantly reduced effect on neurons, compared to the PAI-1 containing CM from senescent astrocytes overexpressing wild type PAI-1 (wtPAI-1), although sdPAI-1 and wtPAI-1 induce similar degree of astrocyte senescence. Together, our results suggest that increased PAI-1, intracellularly or extracellularly, may contribute to brain cell senescence in LOAD and that senescent astrocytes can induce neuron apoptosis through secreting pathologically active molecules, including PAI-1. [ABSTRACT FROM AUTHOR]

Background: Non-pharmacological interventions such as Cognitive Stimulation Therapy (CST) have been shown to help persons living with dementia in improving cognitive function and recall. While previous CST interventions have been conducted largely with community populations, none have explored the outcomes of CST in larger healthcare settings. Our study explored differences of cognitive function, mood, and quality-of-life from CST groups both community and residential-based groups. Method: Participants (N = 258) from academic and rural, hospital-based settings in Missouri engaged in 14-session psychosocial groups to aid reminiscence for enhanced cognitive function and recall. Results: Post-intervention cognitive function improvements occurred for community (t = −7.48, p <.001) and residential samples (t = −2.46, p <.05). Community groups showed significant improvement in overall mood related to their dementia (t = 6.37, p <.001). Conclusion: Healthcare providers should consider CST as a supplemental intervention for older patients receiving usual care for dementia-related symptoms. [ABSTRACT FROM AUTHOR]

Falls are a major public health problem for older adults, resulting in injuries and mortality. Screening is recommended to identify the multifactorial fall risks that can be addressed with interventions to prevent future falls. This study examined the utility of using the Rapid Geriatric Assessment (RGA) tool to identify fall risks across multiple settings. RGA data was collected at primary care sites, hospitals, long-term care settings, and community events (n = 8686, 65% female, mean age 77.6). Multinomial logistic regression was used to determine predictors of falls using the RGA. The FRAIL, SARC-F, Rapid Cognitive Screen and SNAQ measures all significantly predicted history of falls. The RGA provides a brief screening that can be used in any setting by multiple providers to identify fall risk. [ABSTRACT FROM AUTHOR]

Objective: We aimed to evaluate the prevalence, clinical determinants, and consequences (falls and hospitalization) of frailty in older adults with mental illness.Design: Retrospective clinical cohort study.Setting: We collected the data in a specialized psychogeriatric ward, in Boston, USA, between July 2018 and June 2019.Participants: Two hundred and fourty-four inpatients aged 65 years old and over.Measurements: Psychiatric diagnosis was based on a multi-professional consensus meeting according to DSM-5 criteria. Frailty was assessed according to two common instruments, that is, the FRAIL questionnaire and the deficit accumulation model (aka Frailty Index [FI]). Multiple linear regression analyses were conducted to evaluate the association between frailty and sample demographics (age, female sex, and non-Caucasian ethnicity) and clinical characteristics (dementia, number of clinical diseases, current infection, number of psychotropic, and non-psychotropic medications in use). Multiple regression between frailty assessments and either falls or number of hospital admissions in the last 6 and 12 months, respectively, were analyzed and adjusted for covariates.Results: Prevalence of frailty was high, that is, 83.6% according to the FI and 55.3% according to the FRAIL questionnaire. Age, the number of clinical (somatic) diseases, and the number of non-psychotropic medications were independently associated with frailty identified by the FRAIL. Dementia, current infection, the number of clinical (somatic) diseases, and the number of non-psychotropic medications were independently associated with frailty according to the FI. Falls were significantly associated with both frailty instruments. However, we found only a significant association for the number of hospital admissions with the FI.Conclusion: Frailty is highly prevalent among geriatric psychiatry inpatients. The FRAIL questionnaire and the FI may capture different forms of frailty dimensions, being the former probably more associated with the phenotype model and the latter more associated with multimorbidity. [ABSTRACT FROM AUTHOR]

Older adults in North America face similar challenges to successful ageing as other adults around the world, including an increased risk of geriatric syndromes and functional decline, limited access to healthcare professionals specialising in geriatrics and constraints on healthcare spending for Long-Term Services and Supports. Geriatrics as a specialty has long been established, along with the creation of a variety of screening tools for early identification of geriatric syndromes. Despite this, workforce shortages in all older adult care service areas have led to significant gaps in care, particularly in community settings. To address these gaps, innovative programs that expand the reach of geriatric specialists and services have been developed. Opportunities exist for further dissemination of these programs and services, as well as for expansion of an ageing capable workforce. [ABSTRACT FROM AUTHOR]

Hospital care of frail older adults is far from optimal. Although some geriatric models of care have been shown to improve outcomes, the effect size is small and models are difficult to fully implement, sustain and replicate. The two root causes for these shortcomings are competing interests (high revenue generating diseases, procedures and surgeries) and current hospital cultures (for example a culture of safety that emphasizes bed alarms and immobility rather than frequent ambulation). Geriatric hospitals would be hospitals completely dedicated to the care of frail older patients, a group which is most vulnerable to the negative consequences of a hospitalization. They would differ from a typical adult hospital because they could implement evidence based principles of successful geriatric models of care on a hospital wide basis, which would make them sustainable and allow for scaling up of proven outcomes. Innovative structural designs, unachievable in a typical adult hospital, would enhance mobility while maintaining safety. Financial viability and stability would be a challenge but should be feasible, likely through affiliation with larger health care systems with other hospitals because of cost savings associated with geriatric models of care (decreased length of stay, increased likelihood of discharge home, without increasing costs). [ABSTRACT FROM AUTHOR]

Physical activity (PA) has been shown to moderate the negative effects of obesity on pro-inflammatory cytokines but its relationship with the adipokine progranulin (PGRN) remains poorly investigated. This study aimed to examine the cross-sectional main and interactive associations of body mass index (BMI) and PA level with circulating PGRN in older adults. Five-hundred and twelve participants aged 70 years and older involved in the Multidomain Alzheimer Preventive Trial (MAPT) study who underwent plasma PGRN measurements (ng/mL) were included. Self-reported PA levels were assessed using questionnaires. People were classified into 3 BMI categories: normal weight, overweight, or obesity. Further categorization using PA tertiles was used to define highly active, moderately active, and low active individuals. Multiple linear regressions were performed in order to test the associations of BMI, PA level, and their interaction with PGRN levels. Multiple linear regressions adjusted by age, sex, diabetes mellitus status, total cholesterol, creatinine level, and MAPT group demonstrated significant interactive associations of BMI status and continuous PA such that in people without obesity, higher PA levels were associated with lower PGRN concentrations, while an opposite pattern was found in individuals with obesity. In addition, continuous BMI was positively associated with circulating PGRN in highly active individuals but not in their less active peers. This cross-sectional study demonstrated reverse patterns in older adults with obesity compared to those without obesity regarding the relationships between PA and PGRN levels. Longitudinal and experimental investigations are required to understand the mechanisms that underlie the present findings. Clinical Trials Registration Number: NCT00672685. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the interaction between weight loss (WL) and plasma amyloid-β 42/40 (Aβ 42/40), neurofilament light chain (NfL), progranulin, and their association with cognitive decline over time among older adults. This 5-year observational approach included 470 participants from the Multidomain Alzheimer Preventive Trial, mean age 76.8 years (SD = 4.5), 59.4% women. WL was defined as ≥5% decrease over the first year. Biomarkers were measured at 12 months. Cognitive function was assessed yearly from 12 months onward by Mini-Mental State Examination (MMSE); Clinical Dementia Rating sum of boxes (CDR-SB); a composite score based on Category Naming Test; Digit Symbol Substitution Test; 10 MMSE orientation items (MMSEO) and free and total recall of the Free and Cued Selective Reminding test; and these tests individually. Twenty-seven participants (5.7%) presented WL. In adjusted analyses, combined WL + lower Aβ 42/40 (≤0.103, lowest quartile) was related with more pronounced 4-year cognitive decline according to CDR-SB (p < .0001) and MMSEO (p = .021), compared with non-WL + higher Aβ 42/40. WL + higher NfL (>94.55 pg/mL, highest quartile) or progranulin (>38.4 ng/mL, 3 higher quartiles) were related with higher cognitive decline according to CDR-SB, MMSE, MMSEO, and composite score (all p < .03), compared with non-WL + lower NfL or higher progranulin. Regrouping progranulin quartiles (Q1-Q3 vs Q4) revealed higher cognitive decline among the WL + lower progranulin group compared with non-WL + lower progranulin. In conclusion, 1-year WL was associated with subsequent higher 4-year cognitive decline among older adults presenting low Aβ 42/40 or high NfL. Future studies combining plasma biomarker assessments and body weight surveillance may be useful for identifying people at risk of cognitive impairment. Clinical trial number: NCT00672685. [ABSTRACT FROM AUTHOR]

We investigated combining a core AD neuropathology measure (plasma amyloid-beta [Aβ] 42/40) with five plasma markers of inflammation, cellular stress, and neurodegeneration to predict cognitive decline. Among 401 participants free of dementia (median [IQR] age, 76 [73–80] years) from the Multidomain Alzheimer Preventive Trial (MAPT), 28 (7.0%) participants developed dementia, and 137 (34.2%) had worsening of clinical dementia rating (CDR) scale over 4 years. In the models utilizing plasma Aβ alone, a tenfold increased risk of incident dementia (nonsignificant) and a fivefold increased risk of worsening CDR were observed as each nature log unit increased in plasma Aβ levels. Models incorporating Aβ plus multiple plasma biomarkers performed similarly to models included Aβ alone in predicting dementia and CDR progression. However, improving Aβ model performance for composite cognitive score (CCS) decline, a proxy of dementia, was observed after including plasma monocyte chemoattractant protein 1 (MCP1) and growth differentiation factor 15 (GDF15) as covariates. Participants with abnormal Aβ, GDF15, and MCP1 presented higher CCS decline (worsening cognitive function) compared to their normal-biomarker counterparts (adjusted β [95% CI], − 0.21 [− 0.35 to − 0.06], p = 0.005). In conclusion, our study found limited added values of multi-biomarkers beyond the basic Aβ models for predicting clinically meaningful cognitive decline among non-demented older adults. However, a combined assessment of inflammatory and cellular stress status with Aβ pathology through measuring plasma biomarkers may improve the evaluation of cognitive performance. [ABSTRACT FROM AUTHOR]

Background: Multiple types of vaccinations are associated with lower risk for dementia, but it is not known if receiving more than one vaccination type is associated with a greater decrease in incident dementia as compared with receiving only one type. We determined if dementia risk is lowest in patients who receive both herpes zoster (HZ) and tetanus, diphtheria, pertussis (Tdap) vaccinations as compared with receipt of only one or the other type of vaccination. Methods: Primary analysis in a Veterans Health Administration (VA) cohort was replicated in private sector medical claims data. Eligible patients were ≥65 years of age and free of dementia for 2 years prior to baseline (VHA n = 80,070; MarketScan n = 129,200). At index, patients either had both HZ and Tdap, only HZ, only Tdap, or neither vaccination. Confounding was controlled with generalized boosted propensity scores and inverse probability of treatment weighting. Competing risk (VHA) and Cox proportional hazard (MarketScan) models estimated the association between vaccination status and incident dementia. Results: VHA patients' mean age was 76.8 ± 7.6 years, 4.4% were female and 90.9% were White, and MarketScan patients' mean age was 70.5 ± 5.9 and 65.4% were female. In both cohorts, having both HZ and Tdap vaccinations compared with no vaccination was significantly associated with lower dementia risk (VHA HR = 0.50; 95% CI: 0.43–0.59; MarketScan HR = 0.58; 95% CI: 0.38–0.89). In both cohorts, compared with neither vaccination, patients with only one or the other vaccination types had a significantly lower risk for dementia. Incident dementia was lower in patients with both vaccinations versus only one vaccination type. Conclusions and Relevance: Receiving two types of vaccinations versus one type was associated with lower dementia risk. Vaccinations may have non‐specific associations with incident dementia. Low cost and accessible, common adult vaccinations may be an overlooked intervention for reducing dementia risk. [ABSTRACT FROM AUTHOR]

Background: In previous studies, plasma neurofilament light chain (NfL) and progranulin (PGRN) levels are associated with cognitive and physical impairment in older individuals. However, evidence of their relationships with frailty is lacking. This study aims to explore the associations of plasma NfL and PGRN levels with frailty in community‐dwelling older adults. Methods: We included 507 older adults (mean [standard deviation] age, 76.7 [4.5] years) with plasma NfL and PGRN measurements from the Multidomain Alzheimer Preventive Trial (MAPT). The timepoint of biomarker measurements, either 12 or 24 months after study enrollment, was defined as the baseline for each participant. Frailty phenotype (robust, pre‐frail, and frail) was assessed at 12, 24, 36, 48, and 60 months by Fried's frailty criteria. The cross‐sectional associations between plasma neurodegenerative biomarkers and frailty severity were examined using logistic regressions. We further used Cox proportional hazard models to evaluate the associations between plasma biomarkers and incident frailty among robust or pre‐frail participants at baseline (n = 403). Results: At baseline, participants with high plasma NfL levels (>93.11 pg/ml [the upper quartile]) had a higher likelihood of pre‐frailty or frailty compared to their normal NfL counterparts (odds ratio = 1.68; 95% confidence interval = 1.10–2.57); however, this association did not remain significant after controlling for covariates. Neither NfL nor PGRN levels showed prospective associations with incident frailty over 4 years. Conclusions: This study failed to find associations of circulating NfL and PGRN levels with frailty among community‐dwelling older adults in adjusted analyses. Whether plasma neurodegenerative markers serve as potential biomarkers of frailty requires further investigation. [ABSTRACT FROM AUTHOR]

Background & Aims: Ageing is a risk factor for diabetes mellitus (DM) and frailty. It is associated with body composition changes including increase in fat mass (FM), central fat distribution, decrease in fat free mass (FFM) and skeletal muscle which are risk factors for DM. This study aims to evaluate gender differences in body composition in pre-frail diabetics and association with physical performance, cognitive function and perceived health. In addition, we aim to explore the association of obesity, sarcopenia, sarcopenic obesity, and body composition in pre-frail older adults to DM status. Methods: Cross-sectional study of 192 pre-frail community dwelling older adults (≥ 65 years). Data was collected on demographics, physical function, cognition, frailty, sarcopenia, perceived health and body composition using the InBody S10. Univariate and multivariate logistic regression were undertaken to explore the association of sarcopenic obesity, obesity, sarcopenia and body composition measures to DM status. Results: There were insignificant within-gender differences for physical function, cognition and body composition, except for a higher prevalence of obesity defined by body mass index (BMI) and body fat percentage (BF%), increased fat mass index(FMI) and fat free mass index(FFMI) in females with DM. There were significant between-gender differences for those with DM where females overall had lower education levels, lower perceived health, higher prevalence of depression and low mental vitality, lower overall physical function (low short physical performance battery scores, low gait speed and hand grip strength), lower cognitive scores, lower muscle mass and muscle quality with higher FMI, FM/FFM and visceral fat area(VFA). BMI, VFA>100 cm2, FMI and FFMI were found to be independently associated with DM status after multivariable adjustment. Conclusion: Within pre-frail DM vs non-DM, there were insignificant differences in body composition, physical function, cognition and perceived health within gender except for FMI, BF% and FFMI in females. There were significant differences between gender in pre-frail DM in muscle mass, quality, functional, cognitive and mental status. Further longitudinal studies are required to understand the pathogenesis, trajectory of DM and protective role of oral hypoglycemics in pre-frail older adults. [ABSTRACT FROM AUTHOR]

Hospital care of frail older adults is far from optimal. Although some geriatric models of care have been shown to improve outcomes, the effect size is small and models are difficult to fully implement, sustain and replicate. The two root causes for these shortcomings are competing interests (high revenue generating diseases, procedures and surgeries) and current hospital cultures (for example a culture of safety that emphasizes bed alarms and immobility rather than frequent ambulation). Geriatric hospitals would be hospitals completely dedicated to the care of frail older patients, a group which is most vulnerable to the negative consequences of a hospitalization. They would differ from a typical adult hospital because they could implement evidence based principles of successful geriatric models of care on a hospital wide basis, which would make them sustainable and allow for scaling up of proven outcomes. Innovative structural designs, unachievable in a typical adult hospital, would enhance mobility while maintaining safety. Financial viability and stability would be a challenge but should be feasible, likely through affiliation with larger health care systems with other hospitals because of cost savings associated with geriatric models of care (decreased length of stay, increased likelihood of discharge home, without increasing costs). [ABSTRACT FROM AUTHOR]

Background: Body mass index (BMI) is an inadequate marker of obesity, and cannot distinguish between fat mass, fat free mass and distribution of adipose tissue. The purpose of this study was twofold. First, to assess cross-sectional relationship of BMI with fat mass index (FMI), fat free mass index (FFMI) and ratio of fat mass to fat free mass (FM/FFM). Second, to study the association of FMI, FFMI and FM/FFM with physical function including sarcopenia, and cognition in pre-frail older adults. Methods: Cross-sectional study of 191 pre-frail participants ≥ 65 years, 57.1% females. Data was collected on demographics, cognition [Montreal Cognitive Assessment (MoCA)], function, frailty, calf circumference, handgrip strength (HGS), short physical performance battery (SPPB) and gait speed. Body composition was measured using InBody S10. FMI, FFMI and FM/FFM were classified into tertiles (T1, T2, T3) with T1 classified as lowest and T3 highest tertile respectively and stratified by BMI. Results: Higher FFMI and lower FM/FFM in the high BMI group were associated with better functional outcomes. Prevalence of low muscle mass was higher in the normal BMI group. FMI and FM/FFM were significantly higher in females and FFMI in males with significant gender differences except for FFMI in ≥ 80 years old. Small calf circumference was significantly less prevalent in the highest tertile of FMI, FM/FMI and FFMI. Prevalence of sarcopenic obesity and low physical function (HGS, gait speed and SPPB scores) were significantly higher in the highest FMI and FM/FFM tertile. Highest FFMI tertile group had higher physical function, higher MoCA scores, lower prevalence of sarcopenic obesity and sarcopenia, After adjustment, highest tertile of FFMI was associated with lower odds of sarcopenia especially in the high BMI group. Highest tertile of FM/FFM was associated with higher odds of sarcopenia. Higher BMI was associated with lower odds of sarcopenia. Conclusion: FFMI and FM/FFM may be a better predictor of functional outcomes in pre-frail older adults than BMI. Cut-off values for healthy BMI values and role of calf circumference as a screening tool for sarcopenia need to be validated in larger population. Health promotion intervention should focus on FFMI increment. [ABSTRACT FROM AUTHOR]

Background: Herpes zoster (HZ) infection increases dementia risk, but it is not known if herpes zoster vaccination is associated with lower risk for dementia. We determined if HZ vaccination, compared to no HZ vaccination, is associated with lower risk for incident dementia. Methods and findings: Data was obtained from Veterans Health Affairs (VHA) medical records (10/1/2008–9/30/2019) with replication in MarketScan® commercial and Medicare claims (1/1/2009-12/31/2018). Eligible patients were ≥65 years of age and free of dementia for two years prior to baseline (VHA n = 136,016; MarketScan n = 172,790). Two index periods (either start of 2011 or 2012) were defined, where patients either had or did not have a HZ vaccination. Confounding was controlled with propensity scores and inverse probability of treatment weighting. Competing risk (VHA) and Cox proportional hazard (MarketScan) models estimated the association between HZ vaccination and incident dementia in all patients and in age (65–69, 70–74, ≥75) and race (White, Black, Other) sub-groups. Sensitivity analysis measured the association between HZ vaccination and incident Alzheimer's dementia (AD). HZ vaccination at index versus no HZ vaccination throughout follow-up. VHA patients mean age was 75.7 (SD±7.4) years, 4.0% were female, 91.2% white and 20.2% had HZ vaccination. MarketScan patients mean age was 69.9 (SD±5.7) years, 65.0% were female and 14.2% had HZ vaccination. In both cohorts, HZ vaccination compared with no vaccination, was significantly associated with lower dementia risk (VHA HR = 0.69; 95%CI: 0.67–0.72; MarketScan HR = 0.65; 95%CI:0.57–0.74). HZ vaccination was not related to dementia risk in MarketScan patients aged 65–69 years. No difference in HZ vaccination to dementia effects were found by race. HZ vaccination was associated with lower risk for AD. Conclusions: HZ vaccination is associated with reduced risk of dementia. Vaccination may provide nonspecific neuroprotection by training the immune system to limit damaging inflammation, or specific neuroprotection that prevents viral cytopathic effects. [ABSTRACT FROM AUTHOR]

Background: Plasma amyloid-beta (Aβ), neurofilament light chain (NfL), and progranulin (PGRN) have been related to multiple neurodegenerative conditions that might affect physical performance. The aim of this study was to explore the relationship between these plasma neurodegenerative markers and physical performance among community-dwelling older adults.Methods: Five hundred and seven older adults (aged 76 ± 5 years) previously recruited in the Multidomain Alzheimer's Preventive Trial, and had received blood and physical performance tests, were included in this study. Plasma Aβ (Aβ 42/Aβ 40 ratio), NfL, and PGRN levels were measured. Physical performance was assessed by handgrip strength and the Short Physical Performance Battery (combining gait speed, chair stands, and balance tests). Physical performance measured at the same time point and after the blood tests were used. Mixed-effect linear models were performed with age, sex, allocation to Multidomain Alzheimer's Preventive Trial group, body mass index, and Mini-Mental State Examination score as covariates.Results: The mean values of Aβ 42/Aβ 40 ratio, NfL, and PGRN were 0.11, 84.06 pg/mL, and 45.43 ng/mL, respectively. At the cross-sectional level, higher plasma NfL was associated with a lower Short Physical Performance Battery score (β = -0.004, 95% CI [-0.007, -0.001]). At the longitudinal level, higher PGRN levels were associated with decreasing handgrip strength over time (β = -0.02, 95% CI [-0.04, -0.007]). All the other associations were statistically nonsignificant.Conclusion: Our findings suggest the possibility of using plasma NfL and PGRN as markers of physical performance in older adults. [ABSTRACT FROM AUTHOR]

Background: Adult vaccinations may reduce risk for dementia. However, it has not been established whether tetanus, diphtheria, pertussis (Tdap) vaccination is associated with incident dementia.Methods: Hypotheses were tested in a Veterans Health Affairs (VHA) cohort and replicated in a MarketScan medical claims cohort. Patients were at least 65 years of age and free of dementia for 2 years prior to index date. Patients either had or did not have a Tdap vaccination by the start of either of the 2 index periods (2011 or 2012). Follow-up continued through 2018. Controls had no Tdap vaccination for the duration of follow-up. Confounding was controlled using entropy balancing. Competing risk (VHA) and Cox proportional hazard (MarketScan) models estimated the association between Tdap vaccination and incident dementia in all patients and age subgroups (65-69, 70-74, and ≥75 years).Results: VHA patients were, on average, 75.6 (SD ± 7.5) years of age, 4% female, and 91.2% were White. MarketScan patients were 69.8 (SD ± 5.6) years of age, on average and 65.4% were female. After controlling for confounding, patients with, compared to without, Tdap vaccination had a significantly lower risk for dementia in both cohorts (VHA: hazard ratio [HR] = 0.58; 95% confidence interval [CI]:0.54-0.63 and MarketScan: HR = 0.58; 95% CI:0.48-0.70).Conclusions: Tdap vaccination was associated with a 42% lower dementia risk in 2 cohorts with different clinical and sociodemographic characteristics. Several vaccine types are linked to decreased dementia risk, suggesting that these associations are due to nonspecific effects on inflammation rather than vaccine-induced pathogen-specific protective effects. [ABSTRACT FROM AUTHOR]

Physical activity (PA) demonstrated benefits on brain health, but its relationship with blood biomarkers of neurodegeneration remains poorly investigated. We explored the cross-sectional associations of PA with blood concentrations of neurofilament light chain (NFL) and beta amyloid (Aβ)42/40. We further examined whether the interaction between PA and these biomarkers was longitudinally related to cognition. Four-hundred and sixty-five nondemented older adults engaged in an interventional study and who had a concomitant assessment of PA levels and blood measurements of NFL (pg/mL) and Aβ 42/40 were analyzed. A composite Z-score combining 4 cognitive tests was used for cognitive assessment up to a 4-year follow-up. Multiple linear regressions demonstrated that people achieving 500-999 and 2000+ MET-min/week of PA had lower (ln)NFL concentrations than their inactive peers. Logistic regressions revealed that achieving at least 90 MET-min/week of PA was associated with a lower probability of having high NFL concentrations (ie, ≥91.961 pg/mL [third quartile]). PA was not associated with (Aβ)42/40. Mixed-model linear regressions demonstrated that the reverse relationship between PA and cognitive decline tended to be more pronounced as Aβ 42/40 increased, while it was dampened with increasing levels of (ln)NFL concentrations. This study demonstrates that PA is associated with blood NFL but not with Aβ 42/40. Furthermore, it suggests that PA may attenuate the negative association between amyloid load and cognition, while having high NFL levels mitigates the favorable relationship between PA and cognition. More investigations on non demented older adults are required for further validation of the present findings. [ABSTRACT FROM AUTHOR]

Neurofilament light chain (NfL) has been associated with cognitive status in multiple neurodegenerative conditions. Studies about plasma NfL and cognitive decline in older adults are still limited. 504 older adults (median age 75 years) who expressed memory complaints were selected from the Multidomain Alzheimer's Preventive Trial (MAPT) and were classified as normal cognition (NC) or mild cognitive impairment (MCI). Cognitive functions were measured as mini mental state examination (MMSE) and composite cognitive score (CCS) over a 4-year period. Plasma NfL was measured at the first or the second year of the MAPT. Mixed-effects linear models were performed to evaluate cross-sectional and longitudinal associations. In the whole population, higher plasma NfL was cross-sectionally associated with lower cognitive functions (MMSE: β = − 0.007, 95% CI [− 0.013, − 0.001]; CCS: β = − 0.003, 95% CI [− 0.006, − 0.001]). In adults with MCI, but not NC, higher plasma NfL was associated with lower CCS at the cross-sectional level (β = − 0.003, 95% CI [− 0.005, − 0.0002]). The upper quartile NfL group further demonstrated more over time decline in CCS (β = − 0.07, 95% CI [− 0.12, − 0.01]) under the MCI status. Plasma NfL can be a promising biomarker of progressive cognition decline in older adults with MCI. [ABSTRACT FROM AUTHOR]

BACKGROUND/OBJECTIVES: To describe a screening and intervention program for geriatric syndromes instituted at a rural healthcare system that utilizes the 4Ms of an age‐friendly health system, and to provide exercise and cognitive stimulation therapy (CST) as part of an age‐friendly health program. DESIGN: Retrospective evaluation of clinical data. SETTING: Rural primary healthcare system. PARTICIPANTS: Older adults aged 65 years and older in Perry County, Missouri. MEASUREMENTS: Screening for geriatric syndromes was done using the Rapid Geriatric Assessment (RGA), which includes the FRAIL, SARC‐F, Simplified Nutritional Appetite Questionnaire (SNAQ), and Rapid Cognitive Screen (RCS). Outcomes for exercise and CST included the Five Times Sit to Stand (FTSS) and Timed Up and Go (TUG) tests, Cornell Scale for Depression in Dementia (CSDD), Saint Louis University Mental Status Examination (SLUMS), and Quality of Life in Alzheimer's Disease (QoL‐AD) measures. RESULTS: The RGA was administered to 1,326 individuals of which 36.5% were frail, 42.1% were sarcopenic, 26.1% were at risk for anorexia, and 20.8% had dementia. Of these receiving exercise therapy, both the FTSS and the TUG were improved at 3 months and 12 to 24 months. In the CST group, SLUMS, QoL‐AD, and CSDD were improved at 7 weeks and 6 to 12 months. CONCLUSION: It is feasible to introduce a screening program for geriatric syndromes and respond to the results with successful exercise and cognitive stimulation therapy programs. [ABSTRACT FROM AUTHOR]

An editorial is presented on the age-friendly health system framework to long term care setting. Topics include American Hospital Association, and Catholic Health Association of the U.S. has established the Age-Friendly Health System (AFHS) initiative to increase quality and effective person-centered healthcare for older adults.

Background: To investigate whether an exercise intervention using the VIVIFRAIL© protocol has benefits for inflammatory and functional parameters in different frailty status.Methods/design: This is a randomized clinical trial in an outpatient geriatrics clinic including older adults ≥60 years. For each frailty state (frail, pre-frail and robust), forty-four volunteers will be randomly allocated to the control group (n = 22) and the intervention group (n = 22) for 12 weeks. In the control group, participants will have meetings of health education while those in the intervention group will be part of a multicomponent exercise program (VIVIFRAIL©) performed five times a week (two times supervised and 3 times of home-based exercises). The primary outcome is a change in the inflammatory profile (a reduction in inflammatory interleukins [IL-6, TNF- α, IL1beta, IL-17, IL-22, CXCL-8, and IL-27] or an increase in anti-inflammatory mediators [IL-10, IL1RA, IL-4]). Secondary outcomes are change in physical performance using the Short Physical Performance Battery, handgrip strength, fatigue, gait speed, dual-task gait speed, depressive symptoms, FRAIL-BR and SARC-F scores, and quality of life at the 12-week period of intervention and after 3 months of follow-up.Discussion: We expect a reduction in inflammatory interleukins or an increase in anti-inflammatory mediators in those who performed the VIVIFRAIL© protocol. The results of the study will imply in a better knowledge about the effect of a low-cost intervention that could be easily replicated in outpatient care for the prevention and treatment of frailty, especially regarding the inflammatory and anti-inflammatory pathways involved in its pathophysiology.Trial Registration: Brazilian Registry of Clinical Trials (RBR-9n5jbw; 01/24/2020). Registred January 2020. http://www.ensaiosclinicos.gov.br/rg/RBR-9n5jbw/ . [ABSTRACT FROM AUTHOR]

Throughout her career, Rosalie Kane made a major impact in her efforts to improve quality of life for persons living in nursing homes. Near the end of her career, she suggested that it was time to "re-imagine long term care and to produce livable age-friendly nursing homes." This brief review focuses on the role of meaningful engagement and person-centered care as the next step in enhancing nursing home care. The importance of activities that strengthen cognitive and/or physical function is stressed, as well as improving socialization to reduce loneliness. [ABSTRACT FROM AUTHOR]

An editorial is presented on the year of the COVID-19 pandemic. Topics include the economy and made politics chaotic, the smallpox was eventually eradicated by 1980, and the epidemics in the 20th century include polio, human immunodeficiency virus infection (HIV/AIDS), Ebola, the Marburg virus and the Zika virus.

OBJECTIVES: To determine the prevalence of fear of falling (FOF) and fear‐related activity restriction (FAR) and their association with frailty, sarcopenia, gait speed and grip strength, cognitive impairment, depression, social isolation, self‐perceived health, and vision. DESIGN: Observational cross‐sectional study. SETTING: Community. PARTICIPANTS: A total of 493 community‐dwelling older adults, 60 years and older. MEASURES: FOF and FAR were assessed using validated single closed‐ended questions. Questionnaire was administered to evaluate frailty (FRAIL scale ‐ Fatigue, Resistance, Aerobic, Illness, and Loss of Weight), sarcopenia (SARC‐F ‐ lifting and carrying 10 pounds, walking across a room, transferring from bed/chair, climbing a flight of 10 stairs, and frequency of falls in the past 1 year), social isolation (six‐item Lubben Social Network Scale), depression (Even Briefer Assessment Scale), cognition (Chinese Mini‐Mental State Examination), and perceived general health and pain (The EuroQol‐5 Dimension (EQ‐5D)and EQ visual analogue scale (EQ VAS)). Binary logistic regression was performed to determine the influence of sociodemographic, medical, functional, and cognitive variables on FOF with/without FAR. RESULTS: Prevalence of FOF was 69.2%, and among them, 38.4% had FAR. Prevalence of FOF with or without FAR in those with sarcopenia was 93.3% and in prefrail/frail was 76.6%. FOF was significantly associated with prefrail/frail (odds ratio (OR) = 2.17; 95% confidence interval (CI) = 1.26–3.73), depression (OR = 4.90; 95% CI = 1.06–22.67), number of medications (OR = 1.28; 95% CI = 1.03–1.59), and female sex (OR = 3.54; 95% CI = 1.82–6.90). FOF + FAR was associated with depression (OR = 5.17; 95% CI = 1.84–14.54) and sarcopenia (OR = 8.13; 95% CI = 1.52–43.41). CONCLUSION: FOF with/without FAR is highly prevalent among community‐dwelling older adults, especially in those with sarcopenia, prefrailty, and frailty, with significant negative impact on function, quality of life, social network, and mental health. Further research is needed to investigate the value of population‐level screening, causal relationship, and efficacy of comprehensive intervention strategies. [ABSTRACT FROM AUTHOR]

Background and objective: A recent study identified progranulin as a candidate biomarker for frailty, based on gene expression databases. In the present study, we investigated associations between serum progranulin levels and frailty in a population-based sample of late middle-age and older adults. Methods: We utilized a cohort study that included 358 African Americans (baseline ages 49–65). Frailty was assessed by three established methods: the interview-based FRAIL scale, the Cardiovascular Health Study (CHS) frailty scale that includes performance-based measurements, and the Frailty Index (FI) that is based on cumulative deficits. Serum levels of the following proteins and metabolites were measured: progranulin, cystatin C, fructosamine, soluble cytokine receptors (interleukin-2 and -6, tumor necrosis factor α-1 and -2), and C-reactive protein. Sarcopenia was assessed using the SARC-F index. Vital status was determined by matching through the National Death Index (NDI). Results: Serum progranulin levels were associated with frailty for all indices (FRAIL, CHS, and FI) but not with sarcopenia. Inflammatory markers indicated by soluble cytokine receptors (sIL-2R, sIL-6R, sTNFR1, sTNFR2) were positively associated serum progranulin. Increased serum progranulin levels at baseline predicted poorer outcomes including future frailty as measured by the FRAIL scale and 15-year all-cause mortality independent of age, gender, and frailty. Conclusions: Our findings suggest that serum progranulin levels may be a candidate biomarker for physical frailty, independent of sarcopenia. Further studies are needed to validate this association and assess the utility of serum progranulin levels as a potential biomarker for prevalent frailty, for risk for developing incident frailty, and for mortality risk over and above the effect of baseline frailty. [ABSTRACT FROM AUTHOR]

The article discusses that the Frailty is a syndrome which increases the risk of an older person to develop disability or to die when exposed either to physical or psychosocial stressors. Topics discussed include suggest practical frailty screening and management strategies in primary care settings; and discuss the characteristics of these instruments and their applicability to primary care.

Introduction: The geriatric syndromes of frailty, sarcopenia, weight loss, and dementia are highly prevalent in elderly individuals across all care continuums. Despite their deleterious impact on quality of life, disability, and mortality in older adults, they are frequently under-recognized. At Saint Louis University, the Rapid Geriatric Assessment (RGA) was developed as a brief screening tool to identify these four geriatric syndromes. Materials and methods: From 2015–2019, the RGA, comprised of the FRAIL, SARC-F, Simplified Nutritional Appetite Questionnaire (SNAQ), and Rapid Cognitive Screen (RCS) tools and a question on Advance Directives, was administered to 11,344 individuals ≥ 65 years of age across Missouri in community, office-based, hospital, Programs of All-Inclusive Care for the Elderly (PACE), and nursing home care settings. Standard statistical methods were used to calculate the prevalence of frailty, sarcopenia, weight loss, and dementia across the sample. Results: Among the 11,344 individuals screened by the RGA, 41.0% and 30.4% met the screening criteria for pre-frailty and frailty respectively, 42.9% met the screening criteria for sarcopenia, 29.3% were anorectic and at risk for weight loss, and 28.1% screened positive for dementia. The prevalence of frailty, risk for weight loss, sarcopenia, and dementia increased with age and decreased when hospitalized patients and those in the PACE program or nursing home were excluded. Conclusions: Using the RGA as a valid screening tool, the prevalence of one or more of the geriatric syndromes of frailty, sarcopenia, weight loss, and dementia in older adults across all care continuums is quite high. Management approaches exist for each of these syndromes that can improve outcomes. It is suggested that the brief RGA screening tool be administered to persons 65 and older yearly as part of the Medicare Annual Wellness Visit. [ABSTRACT FROM AUTHOR]

Purpose Emerging evidence suggests metformin compared with sulfonylurea is associated with an 8% to 10% lower risk for dementia. Guidelines recommend metformin as initial diabetes treatment, but there is still the question of treatment timing. Thus, the risk of dementia associated with initiating metformin compared with not initiating or delaying treatment was examined. Methods: A retrospective cohort study (1996 to 2015) was conducted with electronic health records from Veteran Health Affairs (VHA; n = 112 845) and Kaiser Permanente Washington (KPW; n = 14 333) healthcare systems. Patients were aged ≥50 years, had a hemoglobin A1c (HbA1c) between 6.5 and <9.5 mg/dL, and did not have dementia or fills for antidiabetic medications before cohort entry. Initiators started metformin monotherapy and noninitiators used no antidiabetic medications in the 6 months after the first qualifying HbA1c. The primary outcome was incident dementia. Propensity scores and inverse probability of treatment weighting (IPTW) controlled for confounding in Cox proportional hazards models. Results: During a median follow‐up of 6.2 years in VHA and 6.8 years in KPW, there were 7547 new dementia cases in VHA and 1090 in KPW. After IPTW, there was no association between initiation of metformin (vs no initial treatment) and incident dementia in VHA (HR = 1.04; 95% confidence interval [CI]: 0.95‐1.13) or KPW (HR = 0.81; 95% CI: 0.51‐1.28). Results did not differ by age, baseline HbA1c, or race. Conclusions: Results do not support initiating metformin earlier to prevent cognitive decline and, thus, may dampen enthusiasm for metformin as a potential antidementia drug. Randomized clinical trials could help clarify the relationship between metformin and cognitive decline. [ABSTRACT FROM AUTHOR]

An editorial is presented on sexuality, ageing, and dementia. Topics discussed include engaged in intimate relationships and viewed sexuality as an important part of their lives; sexual development is a lifelong process, and the presence of a degenerative disease associated with dementia; and physician barriers to discussing sexual health include pervasive stereotypes of sexuality and aging.

The article discusses that Cardiac syncope can be due to tachycardia, bradycardia, asystole, prolonged QT, hypertrophic obstructive cardiac myopathy, amyloid cardiac infiltration, or Brugada syndrome. It mentions that persons with autonomic neuropathy are at high risk of having lethal arrythmias; and also mentions the fall in blood pressure is mainly due to carbohydrates in meals.

An editorial is presented on factors that are a geriatrician's life. Topics discussed include the major feature of the recognition of geriatric syndromes; development of screening tests as backbone of geriatrics; and sarcopenia suggested that it should be redefined as loss of function like grip strength or walking speed in the presence of muscle mass.

Aim: To assess the addition of linagliptin as an alternative to insulin uptitration in older people with type 2 diabetes on stable insulin therapy. Materials and Methods: This phase 4, randomized, multicentre, double‐blinded, placebo‐controlled, 24‐week study recruited individuals on stable insulin, with baseline HbA1c 7.0%‐10.0%, aged ≥60 years and body mass index ≤45 kg/m2. HbA1c and fasting plasma glucose were measured at study visits, and participants assessed glycaemic control with a self‐monitoring blood glucose device. Adverse events (AEs) were reported during the study. Results: Three hundred and two participants were randomized 1:1 to linagliptin 5 mg qd and placebo, with one third of patients from Japan. Study population age and HbA1c (baseline mean ± SD) were 72.4 ± 5.4 years and 8.2 ± 0.8%, respectively; ~80% of participants were aged ≥70 years; 80% had macrovascular complications, one third had a baseline estimated glomerular filtration rate <60 mL/min/1.73 m2; and half had been diagnosed with diabetes for >15 years. Linagliptin significantly improved glucose control at 24 weeks (HbA1c‐adjusted mean change vs. placebo: –0.63%; P <0.0001) and the probability of achieving predefined HbA1c targets without hypoglycaemia (HbA1c <8.0%: OR 2.02; P <0.05 and HbA1c <7.0%: OR 2.44; P <0.01). Linagliptin versus placebo was well tolerated, with similar incidences of AEs, including clinically important hypoglycaemia (blood glucose <54 mg/dL) or severe hypoglycaemia. Conclusions: Addition of linagliptin improves glucose control without an excess of hypoglycaemia in older patients with type 2 diabetes on stable insulin therapy. [ABSTRACT FROM AUTHOR]

The term sarcopenia was introduced in 1988. The original definition was a "muscle loss" of the appendicular muscle mass in the older people as measured by dual energy x‐ray absorptiometry (DXA). In 2010, the definition was altered to be low muscle mass together with low muscle function and this was agreed upon as reported in a number of consensus papers. The Society of Sarcopenia, Cachexia and Wasting Disorders supports the recommendations of more recent consensus conferences, i.e. that rapid screening, such as with the SARC‐F questionnaire, should be utilized with a formal diagnosis being made by measuring grip strength or chair stand together with DXA estimation of appendicular muscle mass (indexed for height2). Assessments of the utility of ultrasound and creatine dilution techniques are ongoing. Use of ultrasound may not be easily reproducible. Primary sarcopenia is aging associated (mediated) loss of muscle mass. Secondary sarcopenia (or disease‐related sarcopenia) has predominantly focused on loss of muscle mass without the emphasis on muscle function. Diseases that can cause muscle wasting (i.e. secondary sarcopenia) include malignant cancer, COPD, heart failure, and renal failure and others. Management of sarcopenia should consist of resistance exercise in combination with a protein intake of 1 to 1.5 g/kg/day. There is insufficient evidence that vitamin D and anabolic steroids are beneficial. These recommendations apply to both primary (age‐related) sarcopenia and secondary (disease related) sarcopenia. Secondary sarcopenia also needs appropriate treatment of the underlying disease. It is important that primary care health professionals become aware of and make the diagnosis of age‐related and disease‐related sarcopenia. It is important to address the risk factors for sarcopenia, particularly low physical activity and sedentary behavior in the general population, using a life‐long approach. There is a need for more clinical research into the appropriate measurement for muscle mass and the management of sarcopenia. Accordingly, this position statement provides recommendations on the management of sarcopenia and how to progress the knowledge and recognition of sarcopenia. [ABSTRACT FROM AUTHOR]

Research on intranasal delivery of drugs, peptides, and proteins has grown over the past decade as an alternate way to deliver substrates to the brain. Recent work has shown intranasal (INL) delivery of insulin improves memory and cognition in healthy subjects as well as patients with Alzheimer's disease (AD) and in AD mouse models. However, the molecular mechanism(s) for the beneficial effect of insulin on memory are still unclear. Using the SAMP8 mouse model of AD, we investigated the impact of INL insulin on protein and gene expression in brain regions including the olfactory bulb, hypothalamus, and hippocampus. We found genes and proteins in the insulin receptor signaling pathway were not activated by the doses tested. However, we did find the expression of genes present in the hippocampus involved in other pathways, especially those related to inflammation, were altered due to age and with a dose of INL insulin previously shown to improve cognition. These alternate pathways could be targets of insulin when delivered via the INL route to aid in memory improvement. [ABSTRACT FROM AUTHOR]

Frailty has long been an important concept in the practice of geriatric medicine and in gerontological research, but integration and implementation of frailty concepts into clinical practice in the United States has been slow. The National Institute on Aging (NIA) Intramural Research Program and the Johns Hopkins Older Americans Independence Center sponsored a symposium to identify potential barriers that impede the movement of frailty into clinical practice and to highlight opportunities to facilitate the further integration of frailty into clinical practice. Primary and subspecialty care providers, and investigators working to integrate and translate new biological aging knowledge into more specific preventive and treatment strategies for frailty provided the meeting content. Recommendations included a call for more specific language that clarifies conceptual differences between frailty definitions and measurement tools; the development of randomized controlled trials to test whether specific intervention strategies for a variety of conditions differently affect frail and non‐frail individuals; development of implementation studies and therapeutic trials aimed at tailoring care as a function of pragmatic frailty markers; the use of deep learning and dynamic systems approaches to improve the translatability of findings from epidemiological studies; and the incorporation of advances in aging biology, especially focused on mitochondria, stem cells, and senescent cells, toward the further development of biologically targeted intervention and prevention strategies that can be used to treat or prevent frailty. J Am Geriatr Soc 67:1559–1564, 2019 [ABSTRACT FROM AUTHOR]

An editorial is presented on Population Health and aging. The data collected by the population health approach should lead to policy, regulation, and systems level change focusing on the economic, environmental, and social components that can lead to meaningful change in health outcomes for communities. The concept of "Green Space" is a central feature of the World Health Organization's Aging-Friendly Cities program.

Purpose: African American patients are more likely to experience cognitive decline after type 2 diabetes mellitus onset than white patients. Metformin use has been associated with a lower risk of dementia compared with sulfonylureas. Evidence for whether this association differs by race is sparse.Methods: Veterans Health Administration (VHA) medical record data were obtained for 73,761 African American and white patients aged ≥50 years who used the VHA from fiscal years 2000 to 2015. Patients were free of dementia and diabetes medications during fiscal years 2000 and 2001 and subsequently initiated metformin or sulfonylurea monotherapy. For race and age subgroups, Cox proportional hazards models using propensity scores and inverse probability of treatment weighting to control for confounding were computed to measure the association between metformin vs sulfonylurea initiation and incident dementia.Results: After controlling for confounding, among patients aged ≥50 years, metformin vs sulfonylurea use was associated with a significantly lower risk of dementia in African American patients (hazard ratio [HR] = 0.73; 95% CI, 0.6-0.89) but not white patients (HR = 0.96; 95% CI, 0.9-1.03). The strongest magnitude of association between metformin and dementia was observed among African American patients aged 50 to 64 years (HR = 0.6; 95% CI, 0.45-0.81). Among those aged 65 to 74 years, metformin was significantly associated with lower risk of dementia in both races. Metformin was not associated with dementia in patients aged ≥75 years.Conclusions: Metformin vs sulfonylurea initiation was associated with a substantially lower risk of dementia among younger African American patients. These results may point to a novel approach for reducing the risk of dementia in African Americans with type 2 diabetes mellitus. [ABSTRACT FROM AUTHOR]

The article discusses that thin 1958 the World Health Organization (WHO) defined anemia as a hemoglobin concentration less than 13g/dl in men and 12g/dl in women. It mentions the causes of anemia can be classified as those with an elevated reticulocyte index; and also mentions that testosterone levels decline in males with aging, resulting in a lowering of the hemoglobin and hematocrit.

An editorial is presented on the application of senolytics drug and snake oil in the pharmaceutical industry. Topics include minimal evidence for its use in humans especially in the age of personalized medicine which is dependent on genetic background of different individuals; and negligible research regarding its long-term effects in the development of medicines related to cancer.

Alzheimer’s disease currently lacks treatment options that effectively reverse the biological/anatomical pathology and cognitive deficits associated with the disease. Loss of function of the nuclear receptor REV-ERB is associated with reduced cognitive function in mouse models. The effect of enhanced REV-ERB activity on cognitive function has not been examined. In this study, we tested the hypothesis that enhanced REV-ERB function may enhance cognitive function in a model of Alzheimer’s disease. We utilized the REV-ERB agonist SR9009 to pharmacologically activate the activity of REV-ERB in the SAMP8 mouse model of Alzheimer’s disease. SR9009 reversed cognitive dysfunction of an aged SAMP8 mouse in several behavioral assays including novel object recognition, T-maze foot shock avoidance, and lever press operant conditioning task assessments. SR9009 treatment reduced amyloid-β 1–40 and 1–42 levels in the cortex, which is consistent with improved cognitive function. Furthermore, SR9009 treatment led to increased hippocampal PSD-95, cortical synaptophysin expression and the number of synapses suggesting improvement in synaptic function. We conclude that REV-ERB is a potential target for treatment of Alzheimer’s disease. [ABSTRACT FROM AUTHOR]