The association between physical frailty and cognitive performance in older adults aged 60-96 years. Data from the "Good Aging in Skåne" (GÅS) Swedish population study.

Background: The association between physical frailty and performance in different cognitive domains in the absence of cognitive disorders is poorly understood. Hence, we aimed to explore the associations between frailty levels based on the Fried Physical Frailty Phenotype and performance of different cognitive domains. We also aimed to examine the associations between cognitive function and each criterion in the Fried Frailty Scale using the same cognitive domains in a non-dementia population aged 60-96 years. Methods: This cross-sectional study included 4,329 participants aged 60-93 years, drawn from the "Good Aging in Skåne" population study. Frailty indices included handgrip strength, physical endurance, body mass index (BMI), physical activity, and walking speed. Cognitive function was assessed across eight domains: episodic memory, processing speed, semantic memory, verbal fluency, working memory, attention, executive function, and visual perception. We constructed adjusted multiple linear regression models for each cognitive domain, with the frailty levels as the independent variable. Likewise, we constructed linear regression models with each cognitive domain as the dependent variable and frailty criteria as independent variables. Results: Physical frailty was associated with poor performance in episodic memory, processing speed, semantic memory, verbal fluency, working memory, attention, and executive functions (p < 0.001 for all associations). Weaker hand grip strength was independently associated with poorer performance in all cognitive domains (p < 0.001-0.015). Conclusions: Higher levels of frailty were associated with poorer performance in all cognitive domains except visual perception. Describing frailty by considering cognitive functioning may provide a better understanding of frailty.

Mortality risk relationship using standard categorized BMI or knee-height based BMI - does the overweight/lower mortality paradox hold true?

BACKGROUND: The body mass index (BMI) is prone to misclassification of obesity due to age-related height loss and resulting measurement errors. Knee-height based BMI (KH-BMI) has not been previously studied in relation to mortality risk in older adults. AIM: To evaluate the age- and sex-specific mortality risk relationship using classic BMI and knee height predicted BMI (KH-BMI) overweight and obesity in a 15-year follow-up study including older Swedish adults aged 60-93 years. METHODS: A 15-year follow-up study among 2,786 individuals aged ≥ 60 years. Height, weight and KH were measured. KH-predicted height was estimated using formulated gender-specific equations. Classic BMI and KH-BMI (kg/m2) were calculated. Mortality data was obtained from the Swedish death registry. Questionnaires were used to collect data on obesity-related lifestyle factors and comorbidities. RESULTS: Cox regression revealed that using the classic BMI, when comparing with the normal/underweight reference group, there was a mortality risk among overweight men (HR = 0.67, 0.52-0.87), overweight women (HR = 0.79, 0.65-0.97), and obese men (HR = 0.60, 0.41-0.89) aged ≥ 80 years old. Using the KH-BMI, only overweight men and overweight women aged ≥ 80 years had a lower mortality risk, men (HR = 0.71, 0.55-0.92); women (HR = 0.77, 0.62-0.95) after adjusting for obesity-related lifestyle factors and comorbidities. DISCUSSION: There is evidence that obesity is overestimated by the BMI, in comparison with the KH-BMI classification. In terms of mortality risk and after adjusting for height, there remains a paradoxical protective association between overweight and mortality. CONCLUSION: Regardless of classic BMI or KH-BMI estimation, overweight men and women aged ≥ 80 years had a lower mortality risk compared to normal/underweight men and women ≥ 80 years.

The Association between Untreated and Treated Hearing Loss and Cognitive Performance in Men and Women Aged 60-96 Years: Data from the Swedish "Good Aging in Skåne" Population Study.

Background/Objectives: Recent decades have witnessed a sharp increase in research investigating the association between hearing loss and cognitive impairment. Few previous studies have stratified for sex when investigating this issue, where results were inconsistent and require further clarification. Thus, the objective was to investigate the association between self-reported hearing loss and levels of cognitive impairment, stratified for sex. Methods: In this cross-sectional study, data were collected from 2001 to 2016. The study sample consisted of 5075 individuals, 2325 (45.8%) men, mean age 68.3 years, and 2750 (54.2%) women, mean age 70.0 years. Multiple variate ordinal regression models were constructed and adjusted for age, marital status, education, physical activity, depressive mood, hypertension, stroke, diabetes, and use of sedatives to investigate associations between groups of self-reported untreated and treated hearing loss and those reporting no hearing loss in relation to levels of cognitive impairment assessed by the Mini-Mental State Examination scale. Results: In men, treated hearing loss was associated with levels of cognitive impairment, odds ratio (OR) = 1.64, 95% confidence interval (CI) = 1.14-2.36. In women, both untreated hearing loss, (OR = 1.45, CI 1.07-1.98) and treated hearing loss (OR= 1.46, CI 1.06-2.04) were associated with levels of cognitive impairment. Conclusions: Hearing loss was found to be associated with cognitive impairment despite hearing aid use as well as awareness amongst physicians. The introduction of screening programs for hearing loss in older adults could be a crucial step for earlier identification of individuals at higher risk of developing cognitive impairment and dementia.

Effectiveness of integrated person-centered interventions for older people's care: Review of Swedish experiences and experts' perspective.

Older adults have multiple medical and social care needs, requiring a shift toward an integrated person-centered model of care. Our objective was to describe and summarize Swedish experiences of integrated person-centered care by reviewing studies published between 2000 and 2023, and to identify the main challenges and scientific gaps through expert discussions. Seventy-three publications were identified by searching MEDLINE and contacting experts. Interventions were categorized using two World Health Organization frameworks: (1) Integrated Care for Older People (ICOPE), and (2) Integrated People-Centered Health Services (IPCHS). The included 73 publications were derived from 31 unique and heterogeneous interventions pertaining mainly to the micro- and meso-levels. Among publications measuring mortality, 15% were effective. Subjective health outcomes showed improvement in 24% of publications, morbidity outcomes in 42%, disability outcomes in 48%, and service utilization outcomes in 58%. Workshop discussions in Stockholm (Sweden), March 2023, were recorded, transcribed, and summarized. Experts emphasized: (1) lack of rigorous evaluation methods, (2) need for participatory designs, (3) scarcity of macro-level interventions, and (4) importance of transitioning from person- to people-centered integrated care. These challenges could explain the unexpected weak beneficial effects of the interventions on health outcomes, whereas service utilization outcomes were more positively impacted. Finally, we derived a list of recommendations, including the need to engage care organizations in interventions from their inception and to leverage researchers' scientific expertise. Although this review provides a comprehensive snapshot of interventions in the context of Sweden, the findings offer transferable perspectives on the real-world challenges encountered in this field.

Longitudinal trajectories of cognitive decline and cerebral blood flow abnormalities in octogenarian men with normal global cognition.

Aims: Cognitive and perfusion changes have been previously observed in older men with Mini Mental State Examination scores>24 points. We aimed to investigate time change in cognitive domains in a cohort of non-demented men between age 68 and 82, and how they are expressed in regional defects estimated by Cerebral Blood Flow (rCBF). Methods: 103 men at age 81 with MMSE scores >24 (mean 28.4 ± 1.7), no dementia or stroke, were examined with the same cognitive test battery at age 68 and age 81: Synonyms (SRB-1), Block design (SRB-3), Paired Associates, Digit Symbol Substitution and Benton Visual Retention test. rCBF was estimated using 99mTc-HMPAO SPECT at age 82. Results: Between ages 68 and 82 we observed a relative decline (Δ%) of cognitive test scores: SRB-3 and Benton tests, -33.7 % (SD 16,8) and -25.8 % (SD 23.9) respectively, followed by Digit Symbol test: -22,6 % (SD 15,6). The cluster of men (46 %) could be detected, grouped on the largest test score decline and highest overall test predictors' importance in decreasing order: Δ% SRB-3, Δ% Paired Associates, Δ% Digit Symbol, Δ% Benton VR and Δ% SRB-1. Compared to the cluster with stable cognitive functions, it expressed lower rCBF in frontal and parietal lobes, and in subcortical areas. Conclusion: Nearly half of the studied, community-dwelling cohort of non-demented, octogenarian men with MMSE > 24, had a combination of decreasing visuospatial ability and episodic memory during preceding years, expressed by widespread rCBF changes in fronto-subcortical areas.

Chronic kidney disease and its association with cerebral small vessel disease in the general older hypertensive population.

BACKGROUND: Cerebral small vessel disease can be identified using magnetic resonance imaging, and includes white matter hyperintensities, lacunar infarcts, cerebral microbleeds, and brain atrophy. Cerebral small vessel disease and chronic kidney disease share many risk factors, including hypertension. This study aims to explore an association between chronic kidney disease and cerebral small vessel disease, and also to explore the role of hypertension in this relationship. METHODS: With a cross sectional study design, data from 390 older adults was retrieved from the general population study Good Aging in Skåne. Chronic kidney disease was defined as glomerular filtration rate < 60 ml/min/1,73m2. Associations between chronic kidney disease and magnetic resonance imaging markers of cerebral small vessel disease were explored using logistic regression models adjusted for age and sex. In a secondary analysis, the same calculations were performed with the study sample stratified based on hypertension status. RESULTS: In the whole group, adjusted for age and sex, chronic kidney disease was not associated with any markers of cerebral small vessel disease. After stratification by hypertension status and adjusted for age and sex, we observed that chronic kidney disease was associated with cerebral microbleeds (OR 1.93, CI 1.04-3.59, p-value 0.037), as well as with cortical atrophy (OR 2.45, CI 1.34-4.48, p-value 0.004) only in the hypertensive group. In the non-hypertensive group, no associations were observed. CONCLUSIONS: In this exploratory cross-sectional study, we observed that chronic kidney disease was associated with markers of cerebral small vessel disease only in the hypertensive subgroup of a general population of older adults. This might indicate that hypertension is an important link between chronic kidney disease and cerebral small vessel disease. Further studies investigating the relationship between CKD, CSVD, and hypertension are warranted.

Association of systemic anticholinergic medication use and accelerated decrease in lung function in older adults.

Older adults are frequently exposed to medicines with systemic anticholinergic properties, which are linked to increased risk of negative health outcomes. The association between systemic anticholinergics and lung function has not been reported. The aim of this study was to investigate if exposure to systemic anticholinergics influences lung function in older adults. Participants of the southernmost centres of the Swedish National study on Aging and Care (SNAC) were followed from 2001 to 2021. In total, 2936 subjects (2253 from Good Aging in Skåne and 683 from SNAC-B) were included. An extensive medical examination including spirometry assessments was performed during the study visits. The systemic anticholinergic burden was described using the anticholinergic cognitive burden scale. The effect of new use of systemic anticholinergics on the annual change in forced expiratory volume (FEV1s) was estimated using mixed models. During follow-up, 802 (27.3%) participants were exposed to at least one systemic anticholinergic medicine. On average, the FEV1s of participants without systemic anticholinergic exposure decreased 37.2 ml/year (95% CI [33.8; 40.6]) while participants with low and high exposure lose 47.2 ml/year (95% CI [42.4; 52.0]) and 43.7 ml/year (95% CI [25.4; 62.0]). A novel association between new use of medicines with systemic anticholinergic properties and accelerated decrease in lung function in older adults was found. The accelerated decrease is comparable to that observed in smokers. Studies are needed to further explore this potential side effect of systemic anticholinergics.

The association between loneliness, social isolation, and sleep disturbances in older adults: A follow-up study from the Swedish good aging in Skåne project.

Objectives: The aim of this follow-up study was to investigate whether loneliness and social isolation in a sample of older adults, mean age of 67.4 years at baseline examination, were associated with sleep disturbances at re-examination at a mean age of 76.4 years. Methods: The study sample consisted of 2897 participants. Data on loneliness, social isolation, and sleep disturbances were collected through questionnaires and medical examinations. Logistic regression models were constructed to identify associations between levels of loneliness and social isolation at baseline and sleep disturbances at follow-up. Sociodemographic and health-related confounding factors were controlled for in the models. Results: Sleep disturbances were reported by 25.6% (95% CI: 24.0%-27.2%) at baseline and 23.7% (95% CI: 22.1%-25.3%) at re-examination. Odds ratios for sleep disturbances at re-examination in relation to not being lonely or socially isolated were as follows: single occasions of loneliness (OR: 1.37, 95% CI: 1.05-1.78), recurring periods/constant loneliness (OR: 1.92, 95% CI: 1.01-1.99), less severe social isolation (OR: 1.18, 95% CI: 0.78-1.79), and severe social isolation (OR: 1.88, 95% CI: 1.01-3.49). Discussion: Sleep disturbances are common among older adults and are associated with loneliness and social isolation. Healthcare professionals should be aware of the potential effects of loneliness and social isolation when investigating sleep disturbances in older adults.

Epidemiology and Functional Impact of Early Peripheral Neuropathy Signs in Older Adults from a General Population.

INTRODUCTION: Peripheral neuropathy (PN) becomes more common with increasing life expectancy, but general population prevalence estimates are lacking. We investigated an epidemiological distribution of signs of PN among 2,996 community-dwelling participants in Good Aging in Skåne Study, age 60-97, and their impact on physical and autonomic function. METHODS: Signs of PN were measured with Utah Early Neuropathy Scale (UENS). Associations between UENS and physical tests, pain, and dysautonomic phenomena were calculated for each sex, adjusted for age, with estimated marginal means (EMM) and odds ratios (ORs) in four UENS quantiles (Q1-Q4). RESULTS: Participants in Q4 had worse EMM for: time to complete Timed Up and Go test (Q4-Q1: male 10.8-9.6 s; female 11.7-10.2 s), 15 m Walk test (Q4-Q1: male 11.1-9.9 s; female 11.2-10.4 s), and fewer repetitions in Step test (Q4-Q1: male 15.2-17.0 steps; female 14.5-15.8 steps). Higher OR of failing one-leg balance 60 s test {male 2.5 (confidence interval [CI] 95%: 1.7-3.8); female 2.1 (1.1-3.2)}, Foam Pad Balance test (male 4.6 [CI 95%: 3.2-6.7]; female 1.8 [1.3-2.6]), and lower physical quality of life were seen in Q4 compared to Q1. Participants in Q4 had higher OR for walking aid usage, falls, fear of falling, pain, and urinary incontinence, while in males, higher OR for orthostatic intolerance, fecal incontinence, and constipation. CONCLUSIONS: In a general population, 20-25% of older adults who have highest UENS scores, a sensitive measure of early PN, express slower gait, worse balance, lower quality of life, pain, falls and fear of falling, and autonomic symptoms.

Plasma Protein Profiling of Incident Cardiovascular Diseases: A Multisample Evaluation.

BACKGROUND: Proteomic profiling could potentially disclose new pathophysiological pathways for cardiovascular diseases (CVD) and improve prediction at the individual level. We therefore aimed to study the plasma protein profile associated with the incidence of different CVDs. METHODS: Plasma levels of 245 proteins suspected to be linked to CVD or metabolism were measured in 4 Swedish prospective population-based cohorts (SIMPLER [Swedish Infrastructure for Medical Population-Based Life-Course and Environmental Research], ULSAM (Uppsala Longitudinal Study of Adult Men), EpiHealth, and POEM [Prospective Investigation of Obesity, Energy Production, and Metabolism]) comprising 11 869 individuals, free of CVD diagnoses at baseline. Our primary CVD outcome was defined by a combined end point that included either incident myocardial infarction, stroke, or heart failure. RESULTS: Using a discovery/validation approach, 42 proteins were associated with our primary composite end point occurring in 1163 subjects. In separate meta-analyses for each of the 3 CVD outcomes, 49 proteins were related to myocardial infarction, 34 to ischemic stroke, and 109 to heart failure. Thirteen proteins were related to all 3 outcomes. Of those, urokinase plasminogen activator surface receptor, adrenomedullin, and KIM-1 (kidney injury molecule 1) were also related to several markers of subclinical CVD in Prospective Investigation of Obesity, Energy production and Metabolism, reflecting myocardial or arterial pathologies. In prediction analysis, a lasso selection of 11 proteins in ULSAM improved the discrimination of CVD by 3.3% (P<0.0001) in SIMPLER when added to traditional risk factors. CONCLUSIONS: Protein profiling in multiple samples disclosed several new proteins to be associated with subsequent myocardial infarction, stroke, and heart failure, suggesting common pathophysiological pathways for these diseases. KIM-1, urokinase plasminogen activator surface receptor, and adrenomedullin were novel early markers of CVD. A selection of 11 proteins improved the discrimination of CVD.

Plasma levels of per- and polyfluoroalkyl substances (PFAS) and cardiovascular disease - Results from two independent population-based cohorts and a meta-analysis.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are persistent chemicals that have been linked to increased cholesterol levels and thus may have a role in the development of cardiovascular disease (CVD). OBJECTIVES: To investigate associations between PFAS exposure and incident CVD (a combined CVD end-point consisting of myocardial infarction, ischemic stroke, or heart failure) in two independent population-based cohorts in Sweden. In addition, we performed a meta-analysis also including results from previous studies. METHODS: In 2,278 subjects aged 45-75 years from the EpiHealth study, the risk of incident CVD in relation to relative plasma levels of perfluorohexanesulfonic acid (PFHxS), perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) was investigated. Associations between plasma levels of six PFAS and incident CVD were also examined in the PIVUS-study (n = 1,016, all aged 70 years). In addition, a meta-analysis was performed including three previous prospective studies, together with the results from the present study. RESULTS: There were no overall statistically significant associations between levels of the different PFAS and incident CVD, neither in EpiHealth nor in PIVUS. However, there was a significant sex interaction for PFOS in EpiHealth (p = 0.008), and an inverse association could be seen only in men (Men, HR: 0.68, 95 % CI: 0.52, 0.89) (Women, HR: 1.13, 95 % CI: 0.82, 1.55). A meta-analysis of five independent studies regarding PFOA and incident CVD showed a risk ratio (RR) of 0.80 (CI: 0.66, 0.94) when high levels were compared to low levels. CONCLUSIONS: This longitudinal study using data from two population-based cohort studies in Sweden did not indicate any increased risk of incident CVD for moderately elevated PFAS levels. A meta-analysis of five independent cohort studies rather indicated a modest inverse association between PFOA levels and incident CVD, further supporting that increasing PFAS levels are not linked to an increased risk of CVD.

Short-term association between outdoor temperature and the hydration-marker copeptin: a pooled analysis in five cohorts.

BACKGROUND: Whereas outdoor temperature is linked to both mortality and hydration status, the hormone vasopressin, measured through the surrogate copeptin, is a marker of cardiometabolic risk and hydration. We recently showed that copeptin has a seasonal pattern with higher plasma concentration in winter. Here, we aimed to investigate the association between outdoor temperature and copeptin. METHODS: Copeptin was analysed in fasting plasma from five cohorts in Malmö, Sweden (n = 26,753, 49.7% men, age 18-86 years). We utilized a multivariable adjusted non-linear spline model with four knots to investigate the association between short-term temperature (24 h mean apparent) and log copeptin z-score. FINDINGS: We found a distinct non-linear association between temperature and log copeptin z-score, with both moderately low and high temperatures linked to higher copeptin concentration (p < 0.0001). Between 0 °C and nadir at the 75th temperature percentile (corresponding to 14.3 °C), log copeptin decreased 0.13 z-scores (95% CI 0.096; 0.16), which also inversely corresponded to the increase in z-score log copeptin between the nadir and 21.3 °C. INTERPRETATION: The J-shaped association between short-term temperature and copeptin resembles the J-shaped association between temperature and mortality. Whereas the untangling of temperature from other seasonal effects on hydration warrants further study, moderately increased water intake constitutes a feasible intervention to lower vasopressin and might mitigate adverse health effects of both moderately cold and hot outdoor temperatures. FUNDING: Swedish Research Council, Å Wiberg, M Stephen, A Påhlsson, Crafoord and Swedish Heart-Lung Foundations, Swedish Society for Medical Research and Swedish Society of Medicine.

Health and work-related factors as predictors of still being active in working life at age 66 and 72 in a Swedish population: A longitudinal study.

BACKGROUND: Health and work environment are known factors in being active in working life beyond legal retirement. OBJECTIVE: To investigate sociodemographic, health and work environment factors as possible predictors of being active in working life at ages 66 and 72. Secondly, investigate eventual changes over time, shortly after a major reform in the Swedish pension system, and predictors of still being active in working life at age 66. METHODS: We used a longitudinal design with two separate cohorts of people at age 60. One baseline assessment was made in 2001-2003 with two 6 years follow-ups, and one in 2007-2009 with one 6 years follow-up. Data were accessed through a Swedish national population-based study and analysed using logistic regression. To examine possible differences between the two cohorts, interaction terms with each independent variable were analysed. RESULTS: Being a man and working in a profession that requires at least three years of university education predicted that the person would still be active in working life at age 66 and 72. Additionally, having a light level of physical activity at work and being diagnosed with fewer than two diseases, also predicted still being active in working life at age 66. Only physical activity at work showed significant changes over time. CONCLUSION: Shortly after a major reform of the public pension system, there was an increase in participation in working life after age 66 and 72. However, gender, profession, and health factors are still important considerations regarding older people's participation in working life.

The metabolomic profiling of total fat and fat distribution in a multi-cohort study of women and men.

Currently studies aiming for the comprehensive metabolomics profiling of measured total fat (%) as well as fat distribution in both sexes are lacking. In this work, bioimpedance analysis was applied to measure total fat (%) and fat distribution (trunk to leg ratio). Liquid chromatography-mass spectrometry-based untargeted metabolomics was employed to profile the metabolic signatures of total fat (%) and fat distribution in 3447 participants from three Swedish cohorts (EpiHealth, POEM and PIVUS) using a discovery-replication cross-sectional study design. Total fat (%) and fat distribution were associated with 387 and 120 metabolites in the replication cohort, respectively. Enriched metabolic pathways for both total fat (%) and fat distribution included protein synthesis, branched-chain amino acids biosynthesis and metabolism, glycerophospholipid metabolism and sphingolipid metabolism. Four metabolites were mainly related to fat distribution: glutarylcarnitine (C5-DC), 6-bromotryptophan, 1-stearoyl-2-oleoyl-GPI (18:0/18:1) and pseudouridine. Five metabolites showed different associations with fat distribution in men and women: quinolinate, (12Z)-9,10-dihydroxyoctadec-12-enoate (9,10-DiHOME), two sphingomyelins and metabolonic lactone sulfate. To conclude, total fat (%) and fat distribution were associated with a large number of metabolites, but only a few were exclusively associated with fat distribution and of those metabolites some were associated with sex*fat distribution. Whether these metabolites mediate the undesirable effects of obesity on health outcomes remains to be further investigated.

Plasma levels of per- and polyfluoroalkyl substances (PFAS) are associated with altered levels of proteins previously linked to inflammation, metabolism and cardiovascular disease.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) have been linked to immunotoxic and cardiometabolic effects in both experimental and epidemiological studies, but with conflicting results. AIM: The aim of the present study was to investigate potential associations between plasma PFAS levels and plasma levels of preselected proteomic biomarkers previously linked to inflammation, metabolism and cardiovascular disease. METHODS: Three PFAS (perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA) and perfluorohexane sulfonic acid (PFHxS)) were measured by non-targeted metabolomics and 249 proteomic biomarkers were measured by the proximity extension assay (PEA) in plasma from 2,342 individuals within the Epidemiology for Health (EpiHealth) study from Sweden (45-75 years old, 50.6 % men). RESULTS: After adjustment for age and sex, 92% of the significant associations between PFOS concentrations and proteins were inverse (p < 0.0002, Bonferroni-adjusted). The results were not as clear for PFOA and PFHxS, but still with 80% and 64 % of the significant associations with proteins being inverse. After adjustment for age, sex, smoking, education, exercise habits and alcohol consumption, levels of epidermal growth factor receptor (EGFR), and paraoxonase type 3 (PON3) remained positively associated with all three PFAS, while resistin (RETN) and urokinase plasminogen activator surface receptor (uPAR) showed inverse associations with all three PFAS. CONCLUSIONS: Our findings imply that PFAS exposure is cross-sectionally linked to altered levels of proteins previously linked to inflammation, metabolism and cardiovascular disease in middle-aged humans.

Prevalence and functional impact of parkinsonian signs in older adults from the Good Aging in Skåne study.

INTRODUCTION: Mild parkinsonian signs (MPS) have been characterized by several definitions, using the motor part of the Unified Parkinson's Disease Rating Scale (UPDRS). We aimed to investigate the prevalence of MPS and their association with functional level and comorbidities in the oldest old. METHOD: Community-dwelling older adults (n = 559, median age 85, range 80-102 years) were examined regarding MPS, possible parkinsonism (PP) and subthreshold parkinsonism (SP) according to four previously used definitions and concerning the impact of parkinsonian signs on cognitive, physical, and autonomic function. MPS, PP and SP are different terms describing a very similar phenomenon and there is no gradation between these. In two of the four definitions more advanced symptoms were categorized as parkinsonism. RESULTS: Median UPDRS score in the whole study group was 10 points (range: 0-58) and was predominated by bradykinesia. MPS/PP/SP were present in 17-85%, and parkinsonism in 33-71% of the cohort. Independently of age and gender, MPS/PP/SP and especially parkinsonism, were associated with a higher risk of fear of falling and accomplished falls, with lower: cognition, ADL, physical activity and quality of life, and with urinary incontinence, obstipation and orthostatic intolerance. CONCLUSIONS: In a population of older adults above 80 years, MPS are highly prevalent as well as more advanced symptoms defined as parkinsonism, and only 9-17% of the cohort is symptom-free. Predominance of bradykinesia in the oldest old might indicate a need for revision of MPS definitions to improve their sensibility.

Cognitive decline and risk of dementia in older adults after diagnosis of chronic obstructive pulmonary disease.

Cognitive screening has been proposed for older adults diagnosed with chronic obstructive pulmonary disease (COPD). Therefore, we examined the change over time in cognitive function and the risk of incident dementia in older adults after COPD diagnosis. A sample of 3,982 participants from the population-based cohort study Good Aging in Skåne was followed for 19 years, and 317 incident COPD cases were identified. The cognitive domains of episodic memory, executive function, and language were assessed using neuropsychological tests. Mixed models for repeated measures and a Cox model were implemented. Participants performed, on average, worse over time on all neuropsychological tests after COPD diagnosis in comparison to those without COPD, although statistical significance differences were only observed for episodic memory and language. The groups had a comparable risk of developing dementia. In conclusion, our results indicate that cognitive screening in the early stages of COPD may be of limited clinical relevance.

Cardiovascular disease-linked plasma proteins are mainly associated with lung volume.

Background: Epidemiological studies have shown that impaired lung function is common and associated with increased risk of cardiovascular disease. Increased levels of several inflammatory and cardiovascular disease-related plasma proteins have been associated with impaired lung function. The aim was to study the association between plasma proteomics and forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC ratio. Methods: We used a discovery and replication approach in two community-based cohorts, EpiHealth and the Malmö Offspring Study (total n=2874), to cross-sectionally study 242 cardiovascular disease- and metabolism-linked proteins in relation to FEV1, FVC (both % predicted) and FEV1/FVC ratio. A false discovery rate of 5% was used as the significance threshold in the discovery cohort. Results: Plasma fatty acid-binding protein 4, interleukin-1 receptor antagonist, interleukin-6 and leptin were negatively associated with FEV1 and paraoxonase 3 was positively associated therewith. Fatty acid-binding protein 4, fibroblast growth factor 21, interleukin-1 receptor antagonist, interleukin-6 and leptin were negatively associated with FVC and agouti-related protein, insulin-like growth factor-binding protein 2, paraoxonase 3 and receptor for advanced glycation end products were positively associated therewith. No proteins were associated with FEV1/FVC ratio. A sensitivity analysis in EpiHealth revealed only minor changes after excluding individuals with known cardiovascular disease, diabetes or obesity. Conclusions: Five proteins were associated with both FEV1 and FVC. Four proteins associated with only FVC and none with FEV1/FVC ratio, suggesting associations mainly through lung volume, not airway obstruction. However, additional studies are needed to investigate underlying mechanisms for these findings.

Associations between per- and polyfluoroalkyl substances (PFAS) and diabetes in two population-based cohort studies from Sweden.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) have been suggested to contribute to the development of metabolic diseases such as obesity, diabetes and non-alcoholic fatty liver disease (NAFLD). However, evidence from epidemiological studies remain divergent. The aim of the present study was to evaluate associations between PFAS exposure and prevalent diabetes in a cross-sectional analysis and fasting glucose in a longitudinal analysis. METHODS: In 2373 subjects aged 45-75 years from the EpiHealth study, three PFAS; perfluorohexanesulfonic acid (PFHxS), perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) were analyzed in plasma together with information on prevalent diabetes. Participants in the PIVUS study (n = 1016 at baseline, all aged 70 years) were followed over 10 years regarding changes in plasma levels of six PFAS; PFHxS, PFOA, PFOS, perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA), and changes in plasma levels of fasting glucose. RESULTS: In the EpiHealth study, no overall associations could be observed between the levels of PFOA, PFOS or PFHxS and prevalent diabetes. However, there was a significant sex-interaction for PFOA (p = 0.02), and an inverse association could be seen between PFOA (on a SD-scale) and prevalent diabetes in women only (OR: 0.71, 95% CI: 0.52, 0.96, p-value: 0.02). This association showed a non-monotonic dose-response curve. In the PIVUS study, inverse relationships could be observed between the changes in levels (ln-transformed) of PFOA and PFUnDA vs the change in fasting glucose levels (ln-transformed) over 10 years (p = 0.04 and p = 0.02, respectively). As in EpiHealth, these inverse associations were significant only in women (PFOA: ß: -0.03, p = 0.02, PFUnDA: ß: -0.03, p = 0.03). IMPACT: Exposure to per- and polyfluoroalkyl substances (PFAS) has been linked to unfavorable human health, including metabolic disorders such as obesity, diabetes and non-alcoholic fatty liver disease. However, results from in vivo, in vitro and epidemiological studies are incoherent. The aim of the present study was therefore to investigate associations between PFAS and diabetes in a cross-sectional study and glucose levels in a longitudinal study. Results show inverse associations in women only. Results also display non-monotonic dose response curves (i.e., that only low levels of PFOA are related to higher probability of prevalent diabetes). This suggests that sex differences and complex molecular mechanisms may underlie the observed findings. A better understanding of the factors and molecular mechanisms contributing to such differences is recognized as an important direction for future research. CONCLUSIONS: PFOA was found to be inversely related to both prevalent diabetes and changes in plasma glucose levels among women only. Thus, our findings suggest there are sex differences in the inverse relationship of PFOA and type 2 diabetes and glucose levels.