Search

Background: We investigated prospectively among community-dwelling older adults aged 65 years and older whether a larger kyphosis angle is associated with poorer physical performance (balance, muscle strength, or both), and whether this association is unidirectional.Methods: Male and female participants performed a multicomponent physical performance test with subscores for gait, muscle strength, and balance at baseline and after 2 years. Hand grip strength was also measured at baseline and at follow-up. The Cobb angle was measured on DXA-based Vertebral Fracture Assessments, made at the baseline and follow-up visit. Through linear and logistic regression analysis, we investigated the association between the kyphosis angle and physical performance and vice versa. We stratified for sex, and tested for effect modification by age and study center.Results: The mean kyphosis angle was 37° and 15% of the participants (n = 1 220, mean age 72.9 ± 5.7 years) had hyperkyphosis (Cobb angle ≥50°). A larger kyphosis angle at baseline was independently associated with a poorer total physical performance score in women of the oldest quartile (≥77 years) in both the cross-sectional and longitudinal analyses (baseline B -0.32, 95% confidence interval [CI] -0.56-0.08; follow-up B 0.32, 95% CI -0.55-0.10). There was no association between physical performance at baseline and kyphosis progression.Conclusion: A larger kyphosis angle is independently associated with a poorer physical performance at baseline and over time, and the direction of this association is unidirectional. These results emphasize the importance of early detection and treatment of hyperkyphosis to prevent further worsening of the kyphosis angle, thereby potentially preserving physical performance. [ABSTRACT FROM AUTHOR]

Studying the genome of centenarians may give insights into the molecular mechanisms underlying extreme human longevity and the escape of age-related diseases. Here, we set out to construct polygenic risk scores (PRSs) for longevity and to investigate the functions of longevityassociated variants. Using a cohort of centenarians with maintained cognitive health (N = 343), a population-matched cohort of older adults from 5 cohorts (N = 2905), and summary statistics data from genome-wide association studies on parental longevity, we constructed a PRS including 330 variants that significantly discriminated between centenarians and older adults. This PRS was also associated with longer survival in an independent sample of younger individuals (p = .02), leading up to a 4-year difference in survival based on common genetic factors only. We show that this PRS was, in part, able to compensate for the deleterious effect of the APOE-ε4 allele. Using an integrative framework, we annotated the 330 variants included in this PRS by the genes they associate with. We find that they are enriched with genes associated with cellular differentiation, developmental processes, and cellular response to stress. Together, our results indicate that an extended human life span is, in part, the result of a constellation of variants each exerting small advantageous effects on aging-related biological mechanisms that maintain overall health and decrease the risk of age-related diseases. [ABSTRACT FROM AUTHOR]

Background: Age-related cognitive decline has large-scale functional and economic consequences and understanding its' pathophysiological mechanisms is therefore essential. Previous research has suggested associations between hormones adiponectin, ghrelin and leptin and neurodegenerative disease. However, their association with age-related cognitive decline has not been fully described. We examine the association between serum high-molecular-weight (HMW) adiponectin, ghrelin and leptin and age-related cognitive decline in older adults.Methods: The associations between HMW adiponectin, ghrelin and leptin and the Mini-Mental-State-Examination, Coding task (Coding), 15 Words Test (15WT) and composite Z-score (general cognitive function) were analyzed by means of a sex-stratified multivariable linear regression analysis in a population-based cohort of 898 older adults at baseline and after 3 years of follow-up.Results: In women, we found a positive association between HMW adiponectin and general cognitive function at baseline (fully adjusted model composite Z-score standardized regression co-efficient beta [β] = .089, p = .025). After 3 years of follow-up, HMW adiponectin was associated with more decline in general cognitive function and information processing speed (fully adjusted model composite Z-score β = -.123, p = .018; Coding β = -.116, p = .027). Ghrelin and leptin were significantly associated with memory in a baseline subgroup analysis of older women. For men, we found no significant associations at baseline or follow-up.Conclusion: Our results show variable associations between hormones HMW adiponectin, ghrelin and leptin and age-related cognitive decline in women but not in men. As there was no clear trend, all our results should be interpreted with caution. [ABSTRACT FROM AUTHOR]

Background: Physical performance is an important factor for successful aging. This study aimed to identify distinct trajectories of multiple physical performance measures over 9 years in individuals aged 60-70 years and to evaluate their characteristics and the overlap between measures.Methods: Four physical performance measures were assessed in 440 participants of the Longitudinal Aging Study Amsterdam: tandem stand, gait speed, chair stand, and handgrip strength. Gender-specific latent class models were conducted to obtain distinct trajectories and their degree of overlap.Results: Mean age at baseline was 67.9 (SD 1.7) years for males and 68.0 (SD 1.7) years for females. The optimal number of trajectories differed across measures. For tandem stand, no distinct trajectories were found (all 179 males, 198 females). For gait speed, three trajectories were identified, dependent on baseline speed: high-stable (47 males, 27 females), intermediate-stable (132 males, 130 females), and low-declining performance (6 males, 48 females). Two trajectories were identified for the chair stand: a stable (168 males, 150 females) and declining trajectory (10 males, 38 females). For handgrip strength, three declining trajectories were identified differing in baseline performance: high (55 males, 75 females), intermediate (111 males, 118 females), and low (17 males, 10 females). Overall, 11.9% of males and 5.7% of females were classified in similar trajectories across measures.Conclusions: Trajectories of physical performance were heterogeneous, but showed similar patterns for males and females. Little overlap between measures was shown, suggesting different mechanisms for decline. This study emphasizes the use of multiple domains to assess physical performance. [ABSTRACT FROM AUTHOR]

Background: Previous studies have suggested that the association between APOE ɛ 4 and dementia is moderated by physical activity (PA), but the results remain inconclusive and longitudinal data on cognitive decline are missing. In this study, we examine whether there is a gene-environment interaction between APOE and PA on cognitive decline in older adults using 9-year follow-up data of three cohort studies.Methods: We followed 7,176 participants from three longitudinal cohort studies: Longitudinal Aging Study Amsterdam (LASA), InCHIANTI, and Rotterdam Study for 9 years. PA was assessed with self-reported questionnaires and was categorized in low, moderate, and high PA. Cognitive function was assessed with the Mini-Mental State Examination (MMSE) and cognitive decline was defined as a decrease of three points or more on the MMSE during 3 years follow-up. We fitted logistic regression models using generalized estimating equations adjusting for age, sex, education, depressive symptoms, and number of chronic disease. Interaction between APOE and PA was tested on multiplicative and additive scale.Results: Cohorts were similar in most aspects but InCHIANTI participants were on average older and had lower education. APOE ɛ 4 carriers had higher odds of cognitive decline (odds ratio [OR] = 1.46, 95% confidence interval [CI]: 1.29-1.64) while PA was not significantly associated with cognitive decline overall (moderate PA: OR = 0.87, 0.67-1.13; high PA: OR = 0.71, 0.36-1.40). There was no evidence for an interaction effect between PA and APOE ɛ 4 in cognitive decline in older adults (APOE × moderate PA: p = .83; APOE × high PA: p = .90).Conclusions: Previous claims of a gene-environment interaction between APOE ɛ 4 and PA in cognitive decline are not supported by our results. [ABSTRACT FROM AUTHOR]

Objective: Previous prospective studies on the association between vitamin D status and depression used a single 25-hydroxyvitamin D (25(OH)D) measurement. We investigated the association between change in serum 25(OH)D and parallel change in depressive symptoms over time in Dutch older adults. Design: A population-based, prospective study in two cohorts of older men and women from the Longitudinal Aging Study Amsterdam. Methods: Serum 25(OH)D concentrations were determined at two time points: in 1995/1996 and 13 years later in the older cohort (aged 65-88y, n = 173) and in 2002/2003 and 6 years later in the younger cohort (55-65 years, n = 450). At these time points, depressive symptoms were measured with the Center for Epidemiologic Studies Depression scale (CES-D). Associations were tested by multiple linear regression analyses. Results: During follow-up, serum 25(OH)D concentrations increased in 32.4% of the older cohort and in 69.8% of the younger cohort. In the older cohort, change in 25(OH)D was not associated with change in CES-D score. In the younger cohort, no associations were observed in participants with higher baseline 25(OH)D concentrations (>58.6 nmol/L), but in those with lower baseline 25(OH)D concentrations, an increase in 25(OH)D was associated with a decrease in CES-D score (adjusted B per 10 nmol/L 25(OH)D increase: -0.62 (95% CI: -1.17, -0.07)). Conclusions: Our study suggests that over 6 years, an increase in serum 25(OH)D is associated with a small decrease in depressive symptoms in young older adults with lower baseline 25(OH)D. Well-designed intervention trials are required to determine causality. [ABSTRACT FROM AUTHOR]

Background: The aim was to investigate the associations of sarcopenia as defined by European Working Group on Sarcopenia in Older People (EWGSOP) and Foundation for the National Institutes of Health (FNIH) Sarcopenia Project, and their underlying components, with the incidence of recurrent falling and fractures.Methods: In 498 older men and women (mean age = 75.2 [SD = 6.4]) from the Longitudinal Aging Study Amsterdam (LASA), the sarcopenia components lean mass (DXA), handgrip strength (handheld dynamometer), and gait speed were measured. Data on falls (3-year follow-up) and fractures (10-year follow-up) were collected. Cox regression analyses were performed, adjusting for age, sex, and total body fat.Results: Recurrent falling occurred in 130 persons and 60 persons experienced a fracture during follow-up. Participants who were identified as sarcopenic based on the FNIH definitions had a more than 2-fold increased risk to become a recurrent faller. There was no association between sarcopenia based on the EWGSOP definition and incidence of recurrent falling. When the sarcopenia components were examined individually, only a low grip strength was associated with incidence of recurrent falling, independent of a low lean mass or a slow gait speed. Sarcopenia according to both definitions was not associated with incident fractures, which may be caused by low statistical power.Conclusion: Sarcopenia according to the FNIH definitions, but not according to the EWGSOP definition was associated with recurrent falling. When examining the individual components, only a low grip strength was independently associated with recurrent falling. No associations between sarcopenia with incidence of fractures were found. [ABSTRACT FROM AUTHOR]

Background: Unhealthy lifestyle factors, such as obesity, smoking, excessive alcohol consumption and physical inactivity, are associated with increased morbidity and mortality risk, even in older age. We investigated trends in lifestyle among three cohorts of adults aged 55-64 years from the Netherlands. Methods: Data from the Longitudinal Aging Study Amsterdam were used. This study consisted of three randomly selected samples of men and women. Lifestyle data were collected in 1992/1993 (cohort 1, n = 988), in 2002/2003 (cohort 2, n = 1002) and in 2012/2013 (cohort 3, n = 1023). Trends in lifestyle across cohorts were tested using multivariable regression analyses. Results: Complete lifestyle data were available for 834 participants from cohort 1, 861 from cohort 2 and 845 from cohort 3. Among men, but not in women, mean BMI and prevalence of obesity increased over time. The mean minutes per day spent being physically active decreased among both men and women, from 130-107 and 230-122 (1992/1993) to 114-100 and 192-109 (2002/2003), and 126-98 and 187-112 (2012/ 2013), respectively. The percentage of men and women defined as excessive drinkers (>7 alcoholic consumptions per week) increased from 54.9%, 62.3% to 65.4% (men) and 22.7%, 36.1% to 37.4% (women), in 1992/1993, 2002/ 2003 and 2012/2013, respectively. The percentage of non-smoking men and women increased over time. Conclusion: The lifestyle of Dutch adults aged 55-64 years was less healthy in 2012/2013 compared with 2002/ 2003 and 1992/1993. Political attention regarding healthy ageing should target the prevention of overweight, physical inactivity and excessive alcohol consumption in middle-aged persons. [ABSTRACT FROM AUTHOR]

Background: several studies have been pointing towards a non-linear relationship between serum 25(OH)D and cardiovascular disease. Next to vitamin D deficiency, also higher levels of 25(OH)D have been reported to be associated with increased cardiovascular risk. We aimed to investigate the nature of the relationship between serum 25(OH)D and measures of arterial stiffness and arteriosclerosis in an elderly population.Design: cross-sectional.Setting/subjects: a subgroup of the B-PROOF study was included to determine associations between serum 25(OH)D and arterial stiffness and atherosclerosis (n = 567, 57% male, age 72.6 ± 5.6 years, mean serum 25(OH)D 54.6 ± 24.1 nmol/l).Methods: carotid intima media thickness (IMT) was assessed using ultrasonography and pulse wave velocity (PWV) was determined with applanation tonometry. Associations were tested using multivariable restricted cubic spline functions and stratified linear regression analysis.Results: the associations between serum 25(OH)D and carotid IMT or PWV were non-linear. Spline functions demonstrated a difference between 25(OH)D deficient and sufficient individuals. In serum 25(OH)D sufficient participants (≥50 nmol/l; n = 287), a positive association with IMT and serum 25(OH)D was present (β 1.24; 95%CI [0.002; 2.473]). PWV levels were slightly lower in vitamin D deficient individuals, but the association with 25(OH)D was not significant.Conclusion: our study demonstrates that associations of serum 25(OH)D and PWV and IMT in an elderly population are not linear. In particular from serum 25(OH)D levels of 50 nmol/l and up, there is a slight increase of IMT with increasing 25(OH)D levels. [ABSTRACT FROM AUTHOR]

Background: poor physical performance (PP) is known to be associated with disability, lower quality of life and higher mortality rates. Knee and hip osteoarthritis (OA) might be expected to contribute to poor PP, through joint pain and restricted range of movement. Both clinical and self-reported OA are often used for large-scale community and epidemiological studies.Objective: to examine the relationships between hip and knee OA and PP in a large data set comprising cohorts from six European countries.Methods: a total of 2,942 men and women aged 65–85 years from the Germany, Italy, Netherlands, Spain, Sweden and the UK were recruited. Assessment included an interview and clinical assessment for OA. PP was determined from walking speed, chair rises and balance (range 0–12); low PP was defined as a score of ≤9.Results: the mean (SD) age was 74.2 (5.1) years. Rates of self-reported OA were much higher than clinical OA. Advanced age, female gender, lower educational attainment, abstinence from alcohol and higher body mass index were independently associated with low PP. Clinical knee OA, hip OA or both were associated with a higher risk of low PP; OR (95% CI) 2.93 (2.36, 3.64), 3.79 (2.49, 5.76) and 7.22 (3.63, 14.38), respectively, with relationships robust to adjustment for the confounders above as well as pain.Conclusion: lower limb OA at the hip and knee is associated with low PP, and for clinical diagnosis relationships are robust to adjustment for pain. Those at highest risk have clinical OA at both sites. [ABSTRACT FROM AUTHOR]

Objective: The role of osteocalcin (OC) in cardiovascular disease (CVD) is unresolved. We aimed to study the association between plasma OC concentrations and the risk of non-fatal and fatal CVDs. We also aimed to investigate whether such an association, if present, would be mediated by established metabolic risk factors. Design: A population-based longitudinal cohort study. Methods: In 1995/1996, OC was determined in blood samples drawn from 1319 subjects aged 65-88 years participating in the Longitudinal Aging Study Amsterdam in 1995/1996. The self-reported CVD events were collected every 3 years until 2005/2006, and CVD deaths until 1st January 2007. Cox proportional hazards regression was performed, considering potential confounders (smoking, physical activity, and BMI) and mediators (blood pressure, plasma triglycerides, total and HDL cholesterol, fructosamine, and aortic calcification). Results: During the median 4.1 years follow-up, 709 subjects (53.8%) suffered a CVD event. There was no overall association betweenOCandCVD: hazard ratio (HR)was 0.97 (95%CI 0.90-1.04) per nmol/l higherplasmaOC, adjusted for age and sex. There was a statistical interaction between plasmaOC, age, and sex on CVD (PZ0.014). In those subjects agedR≥75 years, age-adjusted HRs (95%CI)were 0.86 (0.75-0.99) inmen and 1.16 (1.03-1.31) inwomen pernmol/l higher plasmaOC.Adjustment for covariates only slightly attenuated the association in older-old men, but did not affect the association in older-old women. Conclusion: A higher plasma OC concentration was associated with a reduced risk of CVD in older-old men and with an increased risk of CVD in older-old women. We found no evidence that this was mediated by arterial calcification or metabolic risk factors. [ABSTRACT FROM AUTHOR]

Objective: High as well as low levels of IGF1 have been associated with cardiovascular diseases (CVD). The relationship of IGF1 with (components of) the metabolic syndrome could help to clarify this controversy. The aims of this studywere: i) to investigate the association of IGF1 concentration with prevalent (components of) the metabolic syndrome; and ii) to examine the role of (components of) the metabolic syndrome in the relationship between IGF1 and incident CVD during 11 years of follow-up. Methods: Data were used from the Longitudinal Aging Study Amsterdam, a cohort study in a representative sample of the Dutch older population (⩾65 years). Datawere available in 1258 subjects. Metabolic syndrome was determined using the definition of the US National Cholesterol Education Program Adult Treatment Panel III. CVD were ascertained by self-reports and mortality data. Results: Levels of IGF1 in the fourth quintile were associated with prevalent metabolic syndrome compared with the lowest quintile (odds ratio: 1.59, 95% confidence interval (CI) 1.09-2.33). The middle up to the highest quintile of IGF1 was positively associated with high triglycerides in women. Metabolic syndrome was not a mediator in the U-shaped relationship of IGF1 with CVD. Both subjects without the metabolic syndrome and low IGF1 levels (hazard ratio (HR) 1.75, 95% CI 1.12-2.71) and subjects with the metabolic syndrome and high IGF1 levels (HR 2.28, 95% CI 1.21-4.28) demonstrated increased risks of CVD. Conclusions: In older people, high-normal IGF1 levels are associated with prevalent metabolic syndrome and high triglycerides. Furthermore, this study suggests the presence of different pathomechanisms for both low and high IGF1 levels and incident CVD [ABSTRACT FROM AUTHOR]

Background: Studies suggest an association between a high TSH and (individual components of) the metabolic syndrome. Only a few studies have been performed in the general older population. Objective: This study investigates the association between serum TSH and the metabolic syndrome in a representative sample of older persons in The Netherlands. Design and patients: Data of the Longitudinal Aging Study Amsterdam were used, which is an ongoing cohort study in a representative sample of Dutch older persons. A total of 1187 subjects (590 men and 597 women) between the ages of 65 and 88 years participated in the study. Measurements: Metabolic syndrome (US National Cholesterol Education Program definition) and its individual components were assessed, as well as serum TSH levels. Results: Among the participants, the prevalence of the metabolic syndrome was 34.2%. The mean serum TSH was 1.9 mU/l. Subjects in the upper quartile with a serum TSH level above 2.28 mU/l (odds ratio (OR)Z1.68; 95% confidence interval (CI) 1.19-2.37) had a significantly increased prevalence of metabolic syndrome compared with subjects in the lowest quartile with a serum TSH below 1.04 mU/l. After adjustment for confounders, age, sex, alcohol use, total physical activity, and smoking, the OR was 1.62 (95% CI 1.15-2.32). Conclusions: Subjects with a serum TSH in the upper quartile have a higher prevalence of metabolic syndrome as compared with subjects with a serum TSH in the lowest quartile. [ABSTRACT FROM AUTHOR]

There is increasing evidence that frontotemporal dementia and amyotrophic lateral sclerosis are part of a disease continuum. Recently, a hexanucleotide repeat expansion in C9orf72 was identified as a major cause of both sporadic and familial frontotemporal dementia and amyotrophic lateral sclerosis. The aim of this study was to investigate clinical and neuropathological characteristics of hexanucleotide repeat expansions in C9orf72 in a large cohort of Dutch patients with frontotemporal dementia. Repeat expansions were successfully determined in a cohort of 353 patients with sporadic or familial frontotemporal dementia with or without amyotrophic lateral sclerosis, and 522 neurologically normal controls. Immunohistochemistry was performed in a series of 10 brains from patients carrying expanded repeats using a panel of antibodies. In addition, the presence of RNA containing GGGGCC repeats in paraffin-embedded sections of post-mortem brain tissue was investigated using fluorescence in situ hybridization with a locked nucleic acid probe targeting the GGGGCC repeat. Hexanucleotide repeat expansions in C9orf72 were found in 37 patients with familial (28.7%) and five with sporadic frontotemporal dementia (2.2%). The mean age at onset was 56.9 ± 8.3 years (range 39–76), and disease duration 7.6 ± 4.6 years (range 1–22). The clinical phenotype of these patients varied between the behavioural variant of frontotemporal dementia (n = 34) and primary progressive aphasia (n = 8), with concomitant amyotrophic lateral sclerosis in seven patients. Predominant temporal atrophy on neuroimaging was present in 13 of 32 patients. Pathological examination of the 10 brains from patients carrying expanded repeats revealed frontotemporal lobar degeneration with neuronal transactive response DNA binding protein-positive inclusions of variable type, size and morphology in all brains. Fluorescence in situ hybridization analysis of brain material from patients with the repeat expansion, a microtubule-associated protein tau or a progranulin mutation, and controls did not show RNA-positive inclusions specific for brains with the GGGGCC repeat expansion. The hexanucleotide repeat expansion in C9orf72 is an important cause of frontotemporal dementia with and without amyotrophic lateral sclerosis, and is sometimes associated with primary progressive aphasia. Neuropathological hallmarks include neuronal and glial inclusions, and dystrophic neurites containing transactive response DNA binding protein. Future studies are needed to explain the wide variation in clinical presentation. [ABSTRACT FROM PUBLISHER]

Objective: To what extent endogenous subclinical thyroid disorders contribute to impaired physical and cognitive function, depression, and mortality in older individuals remains a matter of debate. Design: A population-based, prospective cohort of the Longitudinal Aging Study Amsterdam. Methods: TSH and, if necessary, thyroxine and triiodothyronine levels were measured in individuals aged 65 years or older. Participants were classified according to clinical categories of thyroid function. Participants with overt thyroid disease or use of thyroid medication were excluded, leaving 1219 participants for analyses. Outcome measures were physical and cognitive function, depressive symptoms (cross-sectional), and mortality (longitudinal) Results: Sixty-four (5.3%) individuals had subclinical hypothyroidism and 34 (2.8%) individuals had subclinical hyperthyroidism. Compared with euthyroidism (n=1121), subclinical hypo-, and hyperthyroidism were not significantly associated with impairment of physical or cognitive function, or depression. On the contrary, participants with subclinical hypothyroidism did less often report more than one activity limitation (odds ratio 0.44, 95% confidence interval (CI) 0.22-0.86). After a median follow-up of 10.7 years, 601 participants were deceased. Subclinical hypo- and hyper-thyroidism were not associated with increased overall mortality risk (hazard ratio 0.89, 95% CI 0.59-1.35 and 0.69, 95% CI 0.40-1.20 respectively). Conclusions: This study does not support disadvantageous effects of subclinical thyroid disorders on physical or cognitive function, depression, or mortality in an older population. [ABSTRACT FROM AUTHOR]

Background. This study explored the associations between various types of activities, their underlying physical components, and recurrent falling in community-dwelling older persons. Methods. This study included 1,329 community-dwelling persons (≥65 years) of the Longitudinal Aging Study Amsterdam (LASA). The time spent in walking, cycling, light and heavy household activities, and two sports was measured using the LASA Physical Activity Questionnaire (LAPAQ). Physical activity components included strength, intensity, mechanical strain, and turning. Time to second fall in a 6-month period was measured during 3 years with fall calendars. Cox proportional hazards models were adjusted for confounders and stratified for physical performance and sex in case of significant (p < .10) interaction. Results. During 3 years, 325 (24.5%) persons became recurrent fallers. In women, doing light (hazard ratios [HRs] = 0.40, 95% confidence intervals [CIs] = 0.20–0.79) or heavy household activities (HR = 0.63, CI = 0.44–0.79) was associated with a decreased risk of recurrent falling. In persons with good physical performance, doing sports (HR = 1.56, CI = 1.07–2.28), high intensity (HR > 1.75, CI = 1.09–3.16), and high mechanical strain (HR = 1.70, CI = 1.01–2.83) activities was associated with an increased risk of recurrent falling. Conclusions. The results suggest that the relationship between physical activity and recurrent falling differs per type of activity and is modified by physical performance. Doing household activities was associated with a decreased risk of recurrent falling in women. In physically fit older persons, doing sports or activities with high intensity or mechanical strain demands was associated with an increased risk of recurrent falling. [ABSTRACT FROM PUBLISHER]

Long-term gender-affirming hormone therapy (GHT) in older transgender individuals could have beneficial effects on cognitive functioning. Cardiovascular risk factors and psychological factors are known determinants of cognition. Despite the rising number of older transgender individuals, only few studies have examined cognitive functioning in this population. We aimed to assess differences in cognitive functioning between transgender women, and non-transgender (cisgender) women and men, and investigated the contribution of cardiovascular risk factors and psychological factors on these differences. In this study, 37 transgender women (age range 55 to 69) receiving GHT for at least ten years (range 10.2 to 41.6) were examined, and their cognitive functioning was compared to an age and education level matched cohort consisting of 222 cisgender women and men from the Longitudinal Aging Study Amsterdam. Linear regression analyses were performed. Cognitive functioning was assessed by neuropsychological tests including Mini-Mental State Examination (MMSE), Category Fluency animals, Letter Fluency D, 15-Word test (15WT) immediate and delayed recall. Additionally, cardiovascular risk factors and psychological factors such as cardiovascular disease, hypertension, antihypertensive use, statin use, diabetes mellitus, overweight, smoking, alcohol consumption, psychopharmaceutical use, anxiety and depression symptoms were collected. Transgender women had higher MMSE scores compared with cisgender women (+0.9, 95% CI 0.4 to 1.5), and cisgender men (+1.1, 95% CI 0.4 to 1.8). On all other tests transgender women performed similar to cisgender men. Transgender women performed at a lower level than cisgender women on 15WT immediate recall, -5.5, 95% CI -7.6 to -3.4, and 15WT delayed recall, -2.7, 95% CI -3.7 to -1.7, and equal to cisgender women on Fluency animals and Fluency D. Cardiovascular and psychological factors (i.e., cardiovascular disease and depression symptoms) partly explained differences on MMSE score between transgender women and cisgender-control groups. The results of this study do not indicate a need for tailored hormone treatment strategies for older transgender women, based on cognitive aspects after long-term GHT. As one of the first studies, this study compared older transgender women to a large cohort of cisgender men and women regarding cognitive functioning and took into account numerous potential influencing factors. Limitations include difference in test procedures and the cross-sectional design of the study. Cognitive differences between transgender women and cisgender women and men were small, albeit significant. This may suggest that long-term GHT effects on cognitive functioning in older transgender women are minimal. van Heesewijk JO, Dreijerink KMA, Wiepjes CM, et al. Long-Term Gender-Affirming Hormone Therapy and Cognitive Functioning in Older Transgender Women Compared With Cisgender Women and Men. J Sex Med 2021;18:1434–1443. [ABSTRACT FROM AUTHOR]