Food allergies in older people: An emerging health problem.

The prevalence of food allergy (FA) is steadily increasing worldwide. Literature about FA in older people is very scarce since this is predominantly considered as a pediatric condition. However, FA can persist and/or develop across the life course. Given the growing increase in prevalence as well as their persistence, it can be expected that FA will soon represent an important issue in older people. Several age-related factors may potentially mask FA symptoms and/or mediate them in older people. These include mechanisms related to immune senescence, inflammation, and changes in gastrointestinal function as well as micronutrient deficiencies and the use of multiple medications. A multidimensional approach, taking into account the complexity in older people, it is thus important in the evaluation and management of FA during aging. The main and safest strategy in the management of FA is the allergen avoidance since their ingestion may lead to reactions ranging from mild to life-threatening. However, food restrictions should be carefully evaluated, especially in older people, for the risk of nutritional deficiencies and undernutrition.

Frailty in Persons with Down Syndrome: Results from the REVIVIS Study.

OBJECTIVES: To determine frailty prevalence and identify possible nonclinical factors associated with this condition in community-dwelling individuals with Down syndrome (DS). DESIGN: Cross-sectional analysis of the registry study REVIVIS, a single-center, prospective study on the geriatric management of persons with DS. SETTING AND PARTICIPANTS: Individuals with DS (n = 139) referred to a geriatric clinic. METHODS: Frailty was assessed through a 38-item Frailty Index (FI). A multivariable linear regression model was performed to assess the relationship between frailty and different variables of interest: age, number of prescribed drugs, and employment status (unemployed vs employed). RESULTS: Among 139 subjects (54.5% male), mean (SD) aged 42.9 (6.9) years, the median (interquartile range) FI was 0.24 (0.16-0.30) with 60 participants (43.2%) classified as frail. The number of prescribed medications was associated with higher FI levels (P < .001), whereas being employed was associated with lower FI levels (P < .001) compared with being unemployed. No association was found between chronological age and FI. CONCLUSIONS AND IMPLICATIONS: Our findings suggest that chronological age is insufficient to encompass the complexity of a subject with DS, underscoring the importance of a standardized evaluation of the FI among this population. Access to geriatric care might become an important opportunity for people with DS, a population characterized by high vulnerability (or frailty).

Temporal progression of sleep electroencephalography features in isolated rapid eye movement sleep behaviour disorder.

Previous studies indicated that patients with isolated rapid eye movement (REM) sleep behaviour disorder (iRBD) exhibit alterations in spectral electroencephalographic (EEG), spindle, and slow-wave features. As it is currently unknown how these EEG features evolve over time, this study aimed to evaluate their temporal progression in patients with iRBD in comparison to controls. We included 23 patients with iRBD and 23 controls. Two polysomnographies (baseline and follow-up) were recorded with a mean (standard deviation) interval of 4.0 (2.5) years and were automatically analysed for sleep stages, spectral bandpower, spindles, and slow waves. We used linear models to evaluate differences at each time point, and linear mixed-effects models to analyse differences in temporal progression between the groups. At baseline, patients with iRBD presented EEG slowing both in REM (expressed as significantly reduced α-bandpower and increased δ-bandpower in frontal channels) and in non-REM (NREM) sleep (significantly increased slow-to-fast ratio in central channels). These differences vanished at follow-up. In both REM and NREM sleep, γ-bandpower was increased at follow-up in patients with iRBD, resulting in significantly different temporal progression between groups (in occipital channels during REM sleep and frontal channels during NREM sleep). Relative power of sleep spindles was significantly higher at baseline in patients with iRBD in frontal channels, but we observed a significant reduction over time in central channels. Finally, slow waves were significantly shorter in patients with iRBD at both time-points. Our results underscore the need of considering longitudinal data when analysing sleep EEG features in patients with iRBD. The observed temporal changes as markers of progression of neurodegeneration require further investigations.

Post-COVID-19 recovery and geriatric rehabilitation care: a European inter-country comparative study.

PURPOSE: There is variation in organization of geriatric rehabilitation across Europe. The purpose of this study was to describe the selection criteria for referral to geriatric rehabilitation, care provided, and recovery trajectories of post-COVID-19 patients referred to geriatric rehabilitation in Europe. METHODS: This observational cohort study included 723 patients in 59 care facilities for geriatric rehabilitation across 10 countries. Patient data were collected from medical records on admission to geriatric rehabilitation (between September 2020 and October 2021), discharge, 6 weeks and 6 months follow-up. The primary and secondary outcomes were recovery in daily functioning (Barthel Index) and Quality of Life (EQ-5D-5L) from admission to discharge. These were examined using linear mixed models with two levels (measurements nested in patients) and country as an independent variable. Random intercept and random linear slope parameters were added when they improved model fit. A survey about organization of geriatric rehabilitation for post-COVID-19 patients was filled out by country coordinators and data were analyzed using descriptive statistics and inductive coding of answers to open questions. RESULTS: Patients had a mean age of 75.7 years old and 52.4% were male. Many countries used various combinations of the selection criteria, such as functional status, age, frailty, Comprehensive Geriatric Assessment, comorbidities, and cognitive impairments. Most patients received physiotherapy (88.8%) and occupational therapy (69.7%), but there was substantial variance between countries in the percentages of patients that received protein or calorie enriched diets, oxygen therapy, and other treatment components. In all countries, patients showed recovery in daily functioning and quality of life, although there was variation in between countries in rate of recovery. Daily functioning seemed to increase most rapidly in the Czech Republic, Germany, and Russia. The steepest increases in quality of life were seen in the Czech Republic, Germany, and Spain. CONCLUSION: Post-COVID-19 patients showed recovery during geriatric rehabilitation, albeit at variable rates. The observed variation may be explained by the heterogeneity in selection criteria and care provided. This study highlights the need for harmonization of measurements in geriatric rehabilitation order to perform explanatory research and optimize geriatric rehabilitation throughout Europe to ensure optimal patient recovery.

Agreement among different fatigue scales in people with extreme longevity and their offsprings: The FACET experience.

Fatigue is a symptom frequently complained about by older people but unfortunately poorly understood given its subjectivity and the lack of a gold standard for its assessment. The purpose of this study was therefore to preliminarily explore agreement among four different fatigue scales in a sample of persons with extreme longevity (PEL), their direct offsprings (DO), and controls (CO) matched for age and sex with DO. κ statistics was used to quantify agreement among four different fatigue scales. The agreement ranged from mild to substantial and almost perfect agreement depending on the group considered. The highest agreement was found between the Multidimensional Assessment of Fatigue scale and the Short Form Health Survey-36-Vitality Subscale in the PEL group (κ 0.820; 95 % CI 0.471-0.947). These preliminary findings may serve as a guide in selecting the most feasible instrument to assess fatigue in future large-scale research and clinical activities involving older people.

Sex-specific clinical and neurobiological correlates of fatigue in older adults.

Fatigue is a common and distressful symptom in older people and has been associated with adverse health outcomes. Nevertheless, its sex-specific pathophysiological underpinnings and clinical correlates have been scarcely investigated. We aimed to comprehensively explore the clinical and neurobiological determinants of fatigue in cognitively unimpaired older adults. A sex-stratified analysis was conducted to look for differences in the clinical expression of fatigue among women and men. Data on cognitively normal individuals were gathered from the Alzheimer's Disease Neuroimaging Initiative (ADNI) 2 study. Fatigue was defined based on self-report at baseline. For each participant, information on sociodemographics, comorbidities, mood, cognitive performance, frailty, and biomarkers of brain pathology was collected. Logistic regression models, stratified by sex, were conducted to explore the factors associated with fatigue. Among the 291 participants selected, 44 subjects (15.1% of the total sample) self-reported fatigue at baseline. Subjects reporting fatigue were more likely women, had higher frailty degrees, and more severe depressive symptoms than those without fatigue. Moreover, they tended to have lower MRI hippocampus volumes. Among women, those reporting fatigue exhibited higher frailty levels, worse depression, and lower MRI hippocampus volumes relative to those without fatigue. Higher frailty degrees were also observed in men reporting vs. non-reporting fatigue. In the adjusted logistic regression model, more severe depression (OR 1.64, 95% CI 1.18-2.28; p < 0.01) and lower MRI hippocampus volumes (OR 0.41, 95% CI 0.19-0.90; p = 0.03) resulted independently associated with fatigue in women, while higher frailty degrees (OR 3.10, 95% CI 1.27-7.54 per 0.1 increase in a 39-item Frailty index; p = 0.01) in men. Fatigue is a complex symptom with a sex-specific pattern of clinical and neurobiological correlates. A better understanding of the underlying mechanisms of these associations is warranted to develop sex-informed approaches for personalized treatments.

Frailty Is Associated with Malnutrition-Inflammation Syndrome in Older CKD Patients.

Patients affected by chronic kidney disease (CKD) are generally considered to be frailer than those with preserved renal function. We cross-sectionally evaluated the associations between frailty, malnutrition-inflammation syndrome and circulating inflammatory cytokines in 115 older individuals with advanced CKD. As for frailty definition, we adopted Fried's frailty phenotype (FP), while malnutrition-inflammation syndrome was assessed using the Malnutrition-Inflammation Score (MIS) and circulating inflammatory cytokines (IL-6; TNFα; MCP-1). A total of 48 patients were frail, and mean eGFR was comparable in both frail and non-frail patients (24 ± 10 vs. 25 ± 11 mL/min/1.73 m2; p = 0.63). Frail patients had higher MIS (6 [4-11] vs. 4 [3-5]; p < 0.0001) but cytokine concentrations were comparable in both groups. At multivariate regression, FP was independently associated with MIS, age, gender and pre-albumin but not with cytokines. However, we found some associations between inflammatory cytokines and some specific frailty criteria: weight loss and slowness were associated with MCP-1 (respectively p = 0.049 and p < 0.0001) and weakness with IL-6 (p = 0.005); in conclusion, in older patients with advanced CKD, frailty is strictly associated with malnutrition-inflammation syndrome but not with circulating inflammatory cytokines.

Interventions to prevent the onset of frailty in adults aged 60 and older (PRAE-Frail): a systematic review and network meta-analysis.

PURPOSE: Frailty in older adults is associated with multiple adverse health outcomes, while evidence on its successful prevention has been scarce. Therefore, we analyzed the effectiveness of different interventions for the prevention of frailty onset. METHODS: In this systematic review, eight databases were searched for randomized controlled trials of interventions in non-frail (i.e., robust or pre-frail) adults aged ≥ 60 years that assessed frailty incidence at follow-up. Additive component network meta-analysis (CNMA) was conducted to isolate the effect of different intervention types on the main outcome of frailty incidence, reporting relative risk (RR) with 95% confidence intervals (CI). The effect on gait speed was analyzed as an additional outcome using a classic network meta-analysis and the standardized mean difference (SMD) with 95% CI. RESULTS: We screened 24,263 records and identified 11 eligible trials. Nine trials (842 participants, all categorized according to the physical phenotype) in pre-frail (seven RCTs) and robust/pre-frail (two RCTs) older adults were included in the CNMA. Physical exercise significantly reduced frailty incidence at follow-up (RR 0.26, 95% CI 0.08; 0.83), while this was not found for nutritional interventions (RR 1.16, 95% CI 0.33; 4.10). Interventions based on physical exercise also improved gait speed (SMD 1.55, 95% CI 1.16; 1.95). In addition, 22 eligible trial protocols without published results were identified. CONCLUSION: Interventions based on physical exercise appear to be effective in preventing the onset of frailty in older adults. Although the available data are still limited, results from ongoing trials may add to the body of evidence in the foreseeable future.

Relationship of Suboptimal and Disordered Sleep with Cardiovascular Disease and Its Risk Factors - A Narrative Review.

BACKGROUND: Cardiovascular disease (CVD), including coronary heart disease and cerebrovascular disease, is already amongst the leading causes of morbidity and mortality worldwide, but its burden continues to rise. Over time, relevant risk factors for CVD have been identified, many of which are modifiable. More recently, the relationship of sleep and CVD has been of interest, specifically increased rates of disrupted and disordered sleep, which have been found to be associated with CVD. Longitudinal studies have linked sleep difficulties to a predisposition of vascular risk factors, suggesting a potential role for sleep improvement in primary and secondary CVD. SUMMARY: In the present narrative review article, we summarize the current body of research linking suboptimal sleep (e.g., short/long sleep, fragmented sleep) as well as nonbreathing-related sleep disorders (i.e., insomnia, restless legs syndrome/peripheral leg movements of sleep, narcolepsy) to modifiable CVD risk factors and CVD outcomes (morbidity and mortality).

Effect of positive airway pressure treatment on excessive fragmentary myoclonus in 100 sleep-related breathing disorder patients.

STUDY OBJECTIVES: Excessive fragmentary myoclonus (EFM) is a frequent finding in patients undergoing video-polysomnography (VPSG). We aimed to evaluate the potential effect of sleep-related breathing disorder's treatment with positive airway pressure (PAP) therapy on EFM. METHODS: One hundred consecutive patients with EFM and sleep-related breathing disorder subsequently treated with PAP at the sleep lab of the Medical University of Innsbruck, Department of Neurology, Austria, were included. Each patient underwent two nights of VPSG: the first night without and the second night with PAP therapy. Fragmentary myoclonus was automatically scored with validated software, and fragmentary myoclonus index (FMI) and minutes of non-rapid eye movement (NREM) sleep with EFM (minNREM+EFM) were calculated. RESULTS: Under PAP therapy there was a significant decrease in the minNREM+EFM - 60.5 (9.5-161.8) at baseline vs. 37.5 (6.3-168.8) minutes under PAP, p = 0.025. No significant differences were observed for FMI between the two nights. Sleep variables, sleep diagnoses, comorbidities, and medication did not influence FMI or the minNREM+EFM. CONCLUSIONS: The initiation of PAP treatment led to a significant reduction of minNREM+EFM, but not of FMI. The results suggest that PAP therapy might influence the distribution of FM potentials.

Post-COVID-19 patients in geriatric rehabilitation substantially recover in daily functioning and quality of life.

BACKGROUND: After an acute infection, older persons may benefit from geriatric rehabilitation (GR). OBJECTIVES: This study describes the recovery trajectories of post-COVID-19 patients undergoing GR and explores whether frailty is associated with recovery. DESIGN: Multicentre prospective cohort study. SETTING: 59 GR facilities in 10 European countries. PARTICIPANTS: Post-COVID-19 patients admitted to GR between October 2020 and October 2021. METHODS: Patients' characteristics, daily functioning (Barthel index; BI), quality of life (QoL; EQ-5D-5L) and frailty (Clinical Frailty Scale; CFS) were collected at admission, discharge, 6 weeks and 6 months after discharge. We used linear mixed models to examine the trajectories of daily functioning and QoL. RESULTS: 723 participants were included with a mean age of 75 (SD: 9.91) years. Most participants were pre-frail to frail (median [interquartile range] CFS 6.0 [5.0-7.0]) at admission. After admission, the BI first steeply increased from 11.31 with 2.51 (SE 0.15, P < 0.001) points per month and stabilised around 17.0 (quadratic slope: -0.26, SE 0.02, P < 0.001). Similarly, EQ-5D-5L first steeply increased from 0.569 with 0.126 points per month (SE 0.008, P < 0.001) and stabilised around 0.8 (quadratic slope: -0.014, SE 0.001, P < 0.001). Functional recovery rates were independent of frailty level at admission. QoL was lower at admission for frailer participants, but increased faster, stabilising at almost equal QoL values for frail, pre-frail and fit patients. CONCLUSIONS: Post-COVID-19 patients admitted to GR showed substantial recovery in daily functioning and QoL. Frailty at GR admission was not associated with recovery and should not be a reason to exclude patients from GR.

Automatic Spontaneous Speech Analysis for the Detection of Cognitive Functional Decline in Older Adults: Multilanguage Cross-Sectional Study.

BACKGROUND: The rise in life expectancy is associated with an increase in long-term and gradual cognitive decline. Treatment effectiveness is enhanced at the early stage of the disease. Therefore, there is a need to find low-cost and ecological solutions for mass screening of community-dwelling older adults. OBJECTIVE: This work aims to exploit automatic analysis of free speech to identify signs of cognitive function decline. METHODS: A sample of 266 participants older than 65 years were recruited in Italy and Spain and were divided into 3 groups according to their Mini-Mental Status Examination (MMSE) scores. People were asked to tell a story and describe a picture, and voice recordings were used to extract high-level features on different time scales automatically. Based on these features, machine learning algorithms were trained to solve binary and multiclass classification problems by using both mono- and cross-lingual approaches. The algorithms were enriched using Shapley Additive Explanations for model explainability. RESULTS: In the Italian data set, healthy participants (MMSE score≥27) were automatically discriminated from participants with mildly impaired cognitive function (20≤MMSE score≤26) and from those with moderate to severe impairment of cognitive function (11≤MMSE score≤19) with accuracy of 80% and 86%, respectively. Slightly lower performance was achieved in the Spanish and multilanguage data sets. CONCLUSIONS: This work proposes a transparent and unobtrusive assessment method, which might be included in a mobile app for large-scale monitoring of cognitive functionality in older adults. Voice is confirmed to be an important biomarker of cognitive decline due to its noninvasive and easily accessible nature.

Core requirements of frailty screening in the emergency department: an international Delphi consensus study.

INTRODUCTION: Frailty is associated with adverse outcomes among patients attending emergency departments (EDs). While multiple frailty screens are available, little is known about which variables are important to incorporate and how best to facilitate accurate, yet prompt ED screening. To understand the core requirements of frailty screening in ED, we conducted an international, modified, electronic two-round Delphi consensus study. METHODS: A two-round electronic Delphi involving 37 participants from 10 countries was undertaken. Statements were generated from a prior systematic review examining frailty screening instruments in ED (logistic, psychometric and clinimetric properties). Reflexive thematic analysis generated a list of 56 statements for Round 1 (August-September 2021). Four main themes identified were: (i) principles of frailty screening, (ii) practicalities and logistics, (iii) frailty domains and (iv) frailty risk factors. RESULTS: In Round 1, 13/56 statements (23%) were accepted. Following feedback, 22 new statements were created and 35 were re-circulated in Round 2 (October 2021). Of these, 19 (54%) were finally accepted. It was agreed that ideal frailty screens should be short (<5 min), multidimensional and well-calibrated across the spectrum of frailty, reflecting baseline status 2-4 weeks before presentation. Screening should ideally be routine, prompt (<4 h after arrival) and completed at first contact in ED. Functional ability, mobility, cognition, medication use and social factors were identified as the most important variables to include. CONCLUSIONS: Although a clear consensus was reached on important requirements of frailty screening in ED, and variables to include in an ideal screen, more research is required to operationalise screening in clinical practice.

Effects of periodic breathing on sleep at high altitude: a randomized, placebo-controlled, crossover study using inspiratory CO2.

Hypoxia at high altitude facilitates changes in ventilatory control that can lead to nocturnal periodic breathing (nPB). Here, we introduce a placebo-controlled approach to prevent nPB by increasing inspiratory CO2 and used it to assess whether nPB contributes to the adverse effects of hypoxia on sleep architecture. In a randomized, single-blinded, crossover design, 12 men underwent two sojourns (three days/nights each, separated by 4 weeks) in hypobaric hypoxia corresponding to 4000 m altitude, with polysomnography during the first and third night of each sojourn. During all nights, subjects' heads were encompassed by a canopy retaining exhaled CO2 , and CO2 concentration in the canopy (i.e. inspiratory CO2 concentration) was controlled by adjustment of fresh air inflow. Throughout the placebo sojourn inspiratory CO2 was ≤0.2%, whereas throughout the other sojourn it was increased to 1.76% (IQR, 1.07%-2.44%). During the placebo sojourn, total sleep time (TST) with nPB was 54.3% (37.4%-80.8%) and 45.0% (24.5%-56.5%) during the first and the third night, respectively (P = 0.042). Increased inspiratory CO2 reduced TST with nPB by an absolute 38.1% (28.1%-48.1%), the apnoea-hypopnoea index by 58.1/h (40.1-76.1/h), and oxygen desaturation index ≥3% by 56.0/h (38.9.1-73.2/h) (all P < 0.001), whereas it increased the mean arterial oxygen saturation in TST by 2.0% (0.4%-3.5%, P = 0.035). Increased inspiratory CO2 slightly increased the percentage of N3 sleep during the third night (P = 0.045), without other effects on sleep architecture. Increasing inspiratory CO2 effectively prevented hypoxia-induced nPB without affecting sleep macro-architecture, indicating that nPB does not explain the sleep deterioration commonly observed at high altitudes. KEY POINTS: Periodic breathing is common during sleep at high altitude, and it is unclear how this affects sleep architecture. We developed a placebo-controlled approach to prevent nocturnal periodic breathing (nPB) with inspiratory CO2 administration and used it to assess the effects of nPB on sleep in hypobaric hypoxia. Nocturnal periodic breathing was effectively mitigated by an increased inspiratory CO2 fraction in a blinded manner. Prevention of nPB did not lead to relevant changes in sleep architecture in hypobaric hypoxia. We conclude that nPB does not explain the deterioration in sleep architecture commonly observed at high altitude.

Sleep features and long-term incident neurodegeneration: a polysomnographic study.

STUDY OBJECTIVES: Sleep is altered early in neurodegenerative diseases (NDDs) and may contribute to neurodegeneration. Long-term, large sample-size studies assessing NDDs association with objective sleep measures are scant. We aimed to investigate whether video-polysomnography (v-PSG)-based sleep features are associated with long-term NDDs incidence. METHODS: Retrospective cohort study of patients referred 2004-2007 to the Sleep Disorders Unit, Neurology, Medical University Innsbruck, Austria. All patients ≥ 18 years undergoing v-PSG and without NDDs at baseline or within 5 years were included. Main outcome was NDDs diagnosis ≥5 years after v-PSG. RESULTS: Of 1454 patients assessed for eligibility, 999 (68.7%) met inclusion criteria (68.3% men; median age 54.9 (IQR 33.9-62.7) years). Seventy-five patients (7.5%) developed NDDs and 924 (92.5%) remained disease-free after a median of 12.8 (IQR 9.9-14.6) years. After adjusting for demographic, sleep, and clinical covariates, a one-percentage decrease in sleep efficiency, N3-, or rapid-eye-movement (REM)-sleep was associated with 1.9%, 6.5%, or 5.2% increased risk of incident NDDs (HR 1.019, 1.065, and 1.052). One-percentage decrease in wake within sleep period time represented a 2.2% reduced risk of incident NDDs (HR 0.978). Random-forest analysis identified wake, followed by N3 and REM-sleep percentages, as the most important feature associated with NDDs diagnosis. Additionally, multiple sleep features combination improved discrimination of incident NDDs compared to individual sleep stages (concordance-index 0.72). CONCLUSIONS: These findings support contribution of sleep changes to NDDs pathogenesis and provide insights into the temporal window during which these differences are detectable, pointing to sleep as early NDDs marker and potential target of neuroprotective strategies.

Ageism: the -ism affecting the lives of older people living with HIV.

WHO defines ageism as stereotypes, prejudice, and discrimination based on age. Ageism is a multidimensional concept that encompasses multiple components related to the individual, the social group, and the institution in different cultural and environmental settings. In people ageing with HIV these elements include self-stigma, discrimination in society, and experiences in care, many of which are unique to older people. In this Position Paper, we use experience of people with HIV and clinicians taking care of them to explore these issues in high-income countries. The intersectionality of multiple -isms, which affect the lives of older people living with HIV, and ageism enhance several HIV-related issues, including self-inflicted stigma, and loneliness. Research is needed to explore how ageism contributes to worse physical, mental, and social wellbeing outcomes for people with HIV. The model of care for older people living with HIV needs to go beyond virological success by adopting a geriatric mindset, which is attentive to the challenge of ageism and is proactive in promoting a comprehensive approach for the ageing population. All stakeholders and the community should work together to co-create institutional strategies and educational programmes and enable respectful intergenerational dialogue to foster a stigma-free future for older people living with HIV.

Clinical research on extreme longevity: The FACET experience.

People with extreme longevity represent a unique model to study the biology of aging. Unfortunately, their inclusion in research projects is challenging with the consequent lack of evidence and the need to rely on small convenience samples. Given the growing global aging population, especially in the segment of the oldest old (i.e., aged 90 and older), research in this population has become crucial. Furthermore, by studying the characteristics of extremely longeval persons, it might be possible to 1) better understand the mechanisms of aging, and 2) identify endogenous or exogenous factors contributing to a long life. The design and implementation of research activities in the oldest people need special consideration and a pragmatic approach. Possible implementable solutions and suggestions are provided from experience gained during the conduction of the FAtigue in CEnTenarians (FACET) study.

Frailty is associated with the clinical expression of neuropsychological deficits in older adults.

BACKGROUND AND PURPOSE: The aim was to determine whether frailty is associated with the relationship between neuropsychological markers and global cognition in older adults. METHODS: Cross-sectional analyzes were conducted of baseline data from three large cohort studies: National Alzheimer's Coordinating Center (NACC), Rush Memory and Aging Project (MAP) and Alzheimer's Disease Neuroimaging Initiative (ADNI). Studies recruited North American participants along the spectrum of cognitive functioning (44% no cognitive impairment at baseline). A frailty index was computed in each dataset. Frailty indices, neuropsychological tests (including measures of processing speed, episodic, semantic and working memory) and Mini-Mental State Examination (MMSE) scores were the variables of interest, with age, sex, education and apolipoprotein E ε4 evaluated as confounders. RESULTS: Across all studies, 23,819 participants aged 55-104 (57% female) were included in analyzes. Frailty index scores were significantly and inversely associated with MMSE scores and significantly moderated relationships between neuropsychological test scores and MMSE scores. In participants with higher frailty index scores, lower neuropsychological test scores were more strongly associated with lower MMSE scores (standardized interaction coefficients ranged from -0.19 to -1.17 in NACC, -0.03 to -2.27 in MAP and -0.04 to -0.38 in ADNI, depending on the neuropsychological test). These associations were consistent across the different databases and were mostly independent of the composition of frailty indices (i.e., after excluding possible symptoms of dementia). CONCLUSIONS: Amongst older Americans, frailty is associated with the cognitive expression of neuropsychological deficits. Implementation of frailty assessment in routine neurological and neuropsychological practice should be considered to optimize care outcomes for older adults.