Multimorbidity in advanced age and the need for drug treatment may lead to polypharmacy, while pharmacokinetic and pharmacodynamic changes may increase the risk of adverse drug events (ADEs). The aim of this study was to determine the proportion of subjects using potentially inappropriate medication (PIM) in a cohort of older and predominantly healthy adults in relation to polypharmacy and morbidity. Cross-sectional data were available from 1,382 study participants (median age 69 years, IQR 67–71, 51.3% females) of the Berlin Aging Study II (BASE-II). PIM was classified according to the EU(7)-PIM and German PRISCUS (representing a subset of the former) list. Polypharmacy was defined as the concomitant use of at least five drugs. A morbidity index (MI) largely based on the Charlson Index was applied to evaluate the morbidity burden. Overall, 24.1% of the participants were affected by polypharmacy. On average, men used 2 (IQR 1–4) and women 3 drugs (IQR 1–5). According to PRISCUS and EU(7)-PIM, 5.9% and 22.6% of participants received at least one PIM, while use was significantly more prevalent in females (25.5%) compared to males (19.6%) considering EU(7)-PIM (p = 0.01). In addition, morbidity in males receiving PIM according to EU(7)-PIM was higher (median MI 1, IQR 1–3) compared to males without PIM use (median MI 1, IQR 0–2, p<0.001). PIM use occurred more frequently in women than in men, while it was associated with higher morbidity in males. As expected, EU(7)-PIM identifies more subjects as PIM users than the PRISCUS list but further studies are needed to investigate the differential impact of both lists on ADEs and outcome. We found PIM use to be associated with a higher number of regular medications and with increased morbidity. Additionally, we detected a higher prevalence of PIM use in females compared to males, suggesting that women and people needing intensive drug treatment are patient groups, who are particularly affected by PIM use.

Introduction: Medication safety is a vital aim in older adults’ pharmacotherapy. Increased morbidity and vulnerability require particularly careful prescribing. Beneath avoiding unnecessary polypharmacy and prescribing omissions, physicians have to be aware of potentially inappropriate medications (PIMs) and related outcomes to optimize older adults’ drug therapy, and to reduce adverse drug events. Objective: The aim of this study was to identify participants characteristics associated with PIM use and associations of PIM use with functional capacity with a focus on sex differences. Methods: Multivariable logistic regression analyses of cross-sectional Berlin Aging Study II (BASE-II) data (N = 1,382, median age 69 years, interquartile range 67–71, 51.3% women) were performed with PIM classification according to the EU(7)-PIM list. Results: In the overall study population, higher education was associated with lower odds of PIM use (odds ratio [OR] 0.93, confidence interval [CI] 95% 0.87–0.99, p = 0.017). Falls (OR 1.53, CI 95% 1.08–2.17, p = 0.016), frailty/prefrailty (OR 1.68, 1.17–2.41, p = 0.005), and depression (OR 2.12, CI 95% 1.32–3.41, p = 0.002) were associated with increased odds of PIM use. A better nutritional status was associated with lower odds of PIM use (OR 0.88, CI 95% 0.81–0.97, p = 0.008). In the sex-stratified analysis, higher education was associated with lower odds of PIM use in men (OR 0.90, CI 95% 0.82–0.99, p = 0.032). Frailty/prefrailty was associated with increased odds of PIM use in men (OR 2.04, CI 95% 1.18–3.54, p = 0.011) and a better nutritional status was associated with lower odds of PIM use in men (OR 0.83, CI 95% 0.72–0.96, p = 0.011). Falls in the past 12 months were related to an increased prevalence of PIM use in women (OR 1.74, CI 95% 1.10–2.75, p = 0.019). Depression was associated with a higher prevalence of PIM use in both men (OR 2.74, CI 95% 1.20–6.24, p = 0.016) and women (OR 2.06, CI 95% 1.14–3.71, p = 0.017). We did not detect sex differences regarding the overall use of drugs with anticholinergic effects, but more men than women used PIMs referring to the cardiovascular system (p = 0.036), while more women than men used PIMs referring to the genitourinary system and sex hormones (p < 0.001). Conclusion: We found similarities, but also differences between men and women as to the associations between PIM use and participants’ characteristics and functional capacity assessments. The association of lower education with PIM use may suggest that physicians’ prescribing behavior is modified by patient education, a relationship that could evolve from more critical attitudes of educated patients towards medication use. We conclude that sex differences in associations of PIM use with functional capacities might be partly attributable to sex differences in drug classes used, but not with regard to anticholinergics, as these are used to a similar extent in men and women in the cohort studied here.

In genome-wide association studies, genetic variants in the UMOD gene associate with kidney function, blood pressure (BP), and hypertension. Elevated BP is linked to kidney function and impaired cognitive as well as physical performance in later life. We investigated the association between UMOD rs4293393–A > G and kidney function, BP, cognitive and physical function in the Berlin Aging Study II (BASE–II). Data of 1556 older BASE–II participants (mean age 68.2 ± 3.7 years) were analyzed. BP was determined by standardized automated measurements, estimated glomerular filtration rate (eGFR) by CKD Epidemiology Collaboration creatinine equation. Cognitive function was assessed by Mini-Mental State Examination and Digit Symbol Substitution Test, while physical function by Handgrip Strength and Timed Up and Go-Test. Association analyses were performed by covariance and logistic regression models adjusting for sex. G–allele carriers at UMOD rs4293393 exhibited significantly higher eGFR values compared to non–carriers (AA, 76.4 ml/min/1.73 m², CI: 75.7–77.2 vs. AG, 78.4 ml/min/1.73 m², CI: 77.3–79.5 vs. GG, 78.5 ml/min/1.73 m², CI: 75.4–81.7; P = 0.010), and a lower risk of eGFR < 60 mL/min/1.73 m² (AG, OR: 0.63, CI: 0.41–0.97, P = 0.033). However, UMOD rs4293393 genotypes were not associated with BP, diagnosis of hypertension or cognitive and physical function parameters. Our data corroborate previous findings on the association of UMOD rs4293393-G with better kidney function in older adults. However, no association between UMOD and BP or physical and cognitive parameters in these community-dwelling older adults was detected.

The immune system plays a crucial role in the pathogenesis of neurodegenerative diseases. Here, we explored whether blood immune cell profiles are already altered in healthy individuals with a genetic predisposition to amyotrophic lateral sclerosis (ALS) or Alzheimer’s disease (AD). Using multicolor flow cytometry, we analyzed 92 immune cell phenotypes in the blood of 448 healthy participants from the Berlin Aging Study II. We calculated polygenic risk scores (PGSs) using genome-wide significant SNPs from recent large genome-wide association studies on ALS and AD. Linear regression analyses were then performed of the immune cell types on the PGSs in both the overall sample and a subgroup of older participants (>60 years). While we did not find any significant associations between immune cell subtypes and ALS and AD PGSs when controlling for the false discovery rate (FDR = 0.05), we observed several nominally significant results (p < 0.05) with consistent effect directions across strata. The strongest association was observed with CD57+ CD8+ early-memory T cells and ALS risk (p = 0.006). Other immune cell subtypes associated with ALS risk included PD-1+ CD8+ and CD57+ CD4+ early-memory T cells, non-classical monocytes, and myeloid dendritic cells. For AD, naïve CD57+ CD8+ T cells and mature NKG2A+ natural killer cells showed nominally significant associations. We did not observe major immune cell changes in individuals at high genetic risk of ALS or AD, suggesting they may arise later in disease progression. Additional studies are required to validate our nominally significant findings.

While numerous studies have confirmed a causal association between lipoprotein(a) [Lp(a)] and cardiovascular diseases, only a few studies have assessed the relationship between Lp(a) and pulmonary health, with inconsistent findings regarding this topic. This study’s aim was to examine whether levels of serum Lp(a) are associated with lung function in a dataset of relatively healthy older adults. We used longitudinal data collected at two time points 7.4 ± 1.5 years apart from 679 participants (52% women, 68 [65–71] years old) from the Berlin Aging Study II (BASE-II). Multiple linear regression models adjusting for covariates were applied to examine the association between Lp(a) and lung function. The forced expiratory volume in one second (FEV1) and the forced vital capacity (FVC) were higher in both men and women with higher Lp(a) levels. However, since this association between lung function parameters and Lp(a) was not supported by Mendelian randomization analyses using recent genome-wide association study data, these relationships should be investigated in future work, as the observed differences are, in part, considerable and potentially clinically relevant.