New horizons in cognitive and functional impairment as a consequence of cerebral small vessel disease

Cerebral small vessel disease (cSVD) is a frequent finding in imaging of the brain in older adults, especially in the concomitance of cardiovascular disease risk factors. Despite the well-established link between cSVD and (vascular) cognitive impairment (VCI), it remains uncertain how and when these vascular alterations lead to cognitive decline. The extent of acknowledged markers of cSVD is at best modestly associated with the severity of clinical symptoms, but technological advances increasingly allow to identify and quantify the extent and perhaps also the functional impact of cSVD more accurately. This will facilitate a more accurate diagnosis of VCI, against the backdrop of concomitant other neurodegenerative pathology, and help to identify persons with the greatest risk of cognitive and functional deterioration. In this study, we discuss how better assessment of cSVD using refined neuropsychological and comprehensive geriatric assessment as well as modern image analysis techniques may improve diagnosis and possibly the prognosis of VCI. Finally, we discuss new avenues in the treatment of cSVD and outline how these contemporary insights into cSVD can contribute to optimise screening and treatment strategies in older adults with cognitive impairment and multimorbidity.</p

Validation of the ADFICE_IT Models for Predicting Falls and Recurrent Falls in Geriatric Outpatients

Objectives: Before being used in clinical practice, a prediction model should be tested in patients whose data were not used in model development. Previously, we developed the ADFICE_IT models for predicting any fall and recurrent falls, referred as Any_fall and Recur_fall. In this study, we externally validated the models and compared their clinical value to a practical screening strategy where patients are screened for falls history alone. Design: Retrospective, combined analysis of 2 prospective cohorts. Setting and Participants: Data were included of 1125 patients (aged ≥65 years) who visited the geriatrics department or the emergency department. Methods: We evaluated the models' discrimination using the C-statistic. Models were updated using logistic regression if calibration intercept or slope values deviated significantly from their ideal values. Decision curve analysis was applied to compare the models’ clinical value (ie, net benefit) against that of falls history for different decision thresholds. Results: During the 1-year follow-up, 428 participants (42.7%) endured 1 or more falls, and 224 participants (23.1%) endured a recurrent fall (≥2 falls). C-statistic values were 0.66 (95% CI 0.63-0.69) and 0.69 (95% CI 0.65-0.72) for the Any_fall and Recur_fall models, respectively. Any_fall overestimated the fall risk and we therefore updated only its intercept whereas Recur_fall showed good calibration and required no update. Compared with falls history, Any_fall and Recur_fall showed greater net benefit for decision thresholds of 35% to 60% and 15% to 45%, respectively.Conclusions and Implications: The models performed similarly in this data set of geriatric outpatients as in the development sample. This suggests that fall-risk assessment tools that were developed in community-dwelling older adults may perform well in geriatric outpatients. We found that in geriatric outpatients the models have greater clinical value across a wide range of decision thresholds compared with screening for falls history alone.</p

Effectiveness of medication withdrawal in older fallers: Results from the improving medication prescribing to reduce risk of falls (IMPROveFALL) trial

Objectives: to investigate the effect of withdrawal of fall-risk-increasing-drugs (FRIDs) versus 'care as usual' on reducing falls in community-dwelling older fallers. Design: randomised multicentre trial. Participants: six hundred and twelve older adults who visited an Emergency Department (ED) because of a fall. Interventions: withdrawal of FRIDs. Main Outcomes and Measures: primary outcome was time to the first self-reported fall. Secondary outcomes were time to the second self-reported fall and to falls requiring a general practitioner (GP)-consultation or ED-visit. Intention-to-treat (primary) and a per-protocol (secondary) analysis were conducted. The hazard ratios (HRs) for time-to-fall were calculated using a Cox-regression model. Differences in cumulative incidence of falls were analysed using Poisson regression. Results: during 12 months follow-up, 91 (34%) control and 115 (37%) intervention

Quality of life and kidney function in older adults: prospective data of the SCOPE study

Abstract: A longitudinal alteration in health-related quality of life (HRQoL) over a two-year period and its association with early-stage chronic kidney disease (CKD) progression was investigated among 1748 older adults (>75 years). HRQoL was measured by the Euro-Quality of Life Visual Analog Scale (EQ-VAS) at baseline and at one and two years after recruitment. A full comprehensive geriatric assessment was performed, including sociodemographic and clinical characteristics, the Geriatric Depression Scale-Short Form (GDS-SF), Short Physical Performance Baery (SPPB), and estimated glomerular filtration rate (eGFR). The association between EQ-VAS decline and covariates was investigated by multivariable analyses. A total of 41% of the participants showed EQ-VAS decline, and 16.3% showed kidney function decline over the two-year follow-up period. Participants with EQ-VAS decline showed an increase in GDS-SF scores and a greater decline in SPPB scores. The logistic regression analyses showed no contribution of a decrease in kidney function on EQVAS decline in the early stages of CKD. However, older adults with a greater GDS-SF score were more likely to present EQ-VAS decline over time, whereas an increase in the SPPB scores was associated with less EQ-VAS decline. This finding should be considered in clinical practice and when HRQoL is used to evaluate health interventions among older adults

Inflammaging and blood pressure profiles in late life: the screening for CKD among older people across Europe (SCOPE) study

The neutrophil-to-lymphocyte ratio (NLR) is a marker for systemic inflammation. Since inflammation plays a relevant role in vascular aging, the aim of this study was to investigate whether NLR is associated with blood pressure profiles in older adults. This study was performed within the framework of the SCOPE study including 2461 outpatients aged 75 years and over. Mean blood pressure values, namely systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse pressure (PP) were investigated across tertiles of NLR. Change in blood pressure levels in 2 years of follow-up were compared across categories of baseline NLR. Data of 2397 individuals were used, of which 1854 individuals had hypertension. Mean values of blood pressure did not differ across categories of baseline NLR in individuals without hypertension. Individuals with hypertension with a high-range NLR had lower SBP and PP when compared to those in low-range NLR (mean difference SBP −2.94 mmHg, p = 0.032 and PP −2.55 mmHg, p = 0.030). Mean change in blood pressure in 2 years did only slightly differ in non-clinically relevant ranges, when compared across tertiles of baseline NLR. NLR as a marker of inflammaging was not associated with unfavorable blood pressure profiles in older individuals with or without hypertension

Association of genetic variation with systolic and diastolic blood pressure among African Americans: the Candidate Gene Association Resource study

The prevalence of hypertension in African Americans (AAs) is higher than in other US groups; yet, few have performed genome-wide association studies (GWASs) in AA. Among people of European descent, GWASs have identified genetic variants at 13 loci that are associated with blood pressure. It is unknown if these variants confer susceptibility in people of African ancestry. Here, we examined genome-wide and candidate gene associations with systolic blood pressure (SBP) and diastolic blood pressure (DBP) using the Candidate Gene Association Resource (CARe) consortium consisting of 8591 AAs. Genotypes included genome-wide single-nucleotide polymorphism (SNP) data utilizing the Affymetrix 6.0 array with imputation to 2.5 million HapMap SNPs and candidate gene SNP data utilizing a 50K cardiovascular gene-centric array (ITMAT-Broad-CARe [IBC] array). For Affymetrix data, the strongest signal for DBP was rs10474346 (P= 3.6 × 10−8) located near GPR98 and ARRDC3. For SBP, the strongest signal was rs2258119 in C21orf91 (P= 4.7 × 10−8). The top IBC association for SBP was rs2012318 (P= 6.4 × 10−6) near SLC25A42 and for DBP was rs2523586 (P= 1.3 × 10−6) near HLA-B. None of the top variants replicated in additional AA (n = 11 882) or European-American (n = 69 899) cohorts. We replicated previously reported European-American blood pressure SNPs in our AA samples (SH2B3, P= 0.009; TBX3-TBX5, P= 0.03; and CSK-ULK3, P= 0.0004). These genetic loci represent the best evidence of genetic influences on SBP and DBP in AAs to date. More broadly, this work supports that notion that blood pressure among AAs is a trait with genetic underpinnings but also with significant complexit

Association of genetic variation with systolic and diastolic blood pressure among African Americans: the Candidate Gene Association Resource study.

The prevalence of hypertension in African Americans (AAs) is higher than in other US groups; yet, few have performed genome-wide association studies (GWASs) in AA. Among people of European descent, GWASs have identified genetic variants at 13 loci that are associated with blood pressure. It is unknown if these variants confer susceptibility in people of African ancestry. Here, we examined genome-wide and candidate gene associations with systolic blood pressure (SBP) and diastolic blood pressure (DBP) using the Candidate Gene Association Resource (CARe) consortium consisting of 8591 AAs. Genotypes included genome-wide single-nucleotide polymorphism (SNP) data utilizing the Affymetrix 6.0 array with imputation to 2.5 million HapMap SNPs and candidate gene SNP data utilizing a 50K cardiovascular gene-centric array (ITMAT-Broad-CARe [IBC] array). For Affymetrix data, the strongest signal for DBP was rs10474346 (P= 3.6 × 10(-8)) located near GPR98 and ARRDC3. For SBP, the strongest signal was rs2258119 in C21orf91 (P= 4.7 × 10(-8)). The top IBC association for SBP was rs2012318 (P= 6.4 × 10(-6)) near SLC25A42 and for DBP was rs2523586 (P= 1.3 × 10(-6)) near HLA-B. None of the top variants replicated in additional AA (n = 11 882) or European-American (n = 69 899) cohorts. We replicated previously reported European-American blood pressure SNPs in our AA samples (SH2B3, P= 0.009; TBX3-TBX5, P= 0.03; and CSK-ULK3, P= 0.0004). These genetic loci represent the best evidence of genetic influences on SBP and DBP in AAs to date. More broadly, this work supports that notion that blood pressure among AAs is a trait with genetic underpinnings but also with significant complexity

Gender differences in arterial structure and function: Are men really from Mars and women from Venus?

Gender difference of cardiovascular disease is one of the most investigated and still unsolved items. Finding an answer to this, may have important implications for understanding the differences between men and women in atherosclerosis and possibly lead to the development of gender-specific treatment for cardiovascular disease

Anticholinergic Drug Use on Admission and the Risk of In-Hospital Falls in Older Hospitalized Patients

PURPOSE: In-hospital falls, especially among older patients, are a major and underestimated problem. Several studies have suggested a possible association between anticholinergic drug use and falls, but the results are inconclusive and studies focusing on in-hospital falls are scarce. The aim of the present study was to investigate whether anticholinergic drug exposure on admission is associated with in-hospital falls. PATIENTS AND METHODS: This retrospective chart review study was conducted in the Erasmus MC University Medical Center, Rotterdam, the Netherlands. Patients aged 65 years and older, who were acutely admitted to the geriatric ward between 2012 and 2015, were included. Anticholinergic drug exposure was determined with the Anticholinergic Risk Scale (ARS), the Anticholinergic Cognitive Burden scale (ACB) and the list of Chew. Logistic regression was used to investigate the possible association between anticholinergic drug exposure and in-hospital falls. Analyses were adjusted for age, sex, fall history, fall as reason for admission, number of drugs on admission, use of a mobility aid and delirium. RESULTS: A total of 905 patients were included, of which 94 patients experienced one or more in-hospital falls. Each additional anticholinergic drug in use, according to the ARS, was associated with an increased odd of experiencing a fall (OR = 1.49, 95% CI: 1.06–2.10). Other measures, ie anticholinergic drug use (yes/no) and different categories of anticholinergic drug burden, measured with the ARS, ACB and list of Chew, were all not associated with in-hospital falls. CONCLUSION: Anticholinergic drug exposure on admission is possibly not a main risk factor for in-hospital falls among older patients