Frailty as a Predictor of Mortality in Late-Life Depression: A Prospective Clinical Cohort Study.

OBJECTIVE: Frailty is a clinical phenotype that predicts negative health outcomes, including mortality, and is increasingly used for risk stratification in geriatric medicine. Similar to frailty, late-life depression is also associated with increased mortality rates. Therefore, we examined whether frailty and frailty-related biomarkers predict mortality among depressed older patients. METHODS: In our study of 378 older patients aged ≥ 60 years with a depressive disorder (DSM-IV criteria), we examined whether frailty predicts time-to-death during a 6-year follow-up using Cox proportional hazard regression analyses adjusted for confounders. Baseline data were collected from 2007 to September 2010. Frailty was defined according to the Fried Frailty Phenotype criteria (muscle weakness, slowness, exhaustion, low activity level, unintended weight loss). Similarly, we examined the predictive value of 3 inflammatory markers, vitamin D level, and leukocyte telomere length and whether these effects were independent of the frailty phenotype. RESULTS: During follow-up, 27 (26.2%) of 103 frail depressed patients died compared with 35 (12.7%) of 275 non-frail depressed patients (P < .001). Adjusted for confounders, the number of frailty components was associated with an increased mortality rate (hazard ratio = 1.38 [95% CI, 1.06-1.78], P = .015). All biomarkers except for interleukin 6 were prospectively associated with mortality, but only higher levels of high-sensitivity C-reactive protein and lower levels of vitamin D were independent of frailty associated with mortality. CONCLUSIONS: In late-life depression, frailty identifies older patients at increased risk of adverse negative health outcomes. Therefore, among frail depressed patients, treatment models that include frailty-specific interventions might reduce mortality rates.

Vitamin D deficiency and course of frailty in a depressed older population.

Objective: To study the association between vitamin D levels and frailty, its components and course in a depressed sample.Methods: Baseline and two-year follow-up data from the depressed sample of the Netherlands Study of Depression in Older persons (NESDO), a prospective observational cohort study, were analyzed. The 378 participants (aged 60-93) had a diagnosis of depression according to DSM-IV criteria. Frailty was defined according to Fried's physical phenotype. 25-OH vitamin D measurement was performed by liquid chromatography - tandem mass spectrometry. Linear and logistic regression analyses were performed, adjusted for covariates.Results: Higher vitamin D levels were cross-sectionally associated with lower prevalence of frailty (OR 0.64 [95%-CI 0.45 - 0.90], p = .010), predicted a lower incidence of frailty among non-frail depressed patients (OR 0.51 [95%-CI 0.26 - 1.00], p=.050), and, surprisingly, the persistence of frailty among frail depressed patients (OR 2.82 [95%-CI 1.23 - 6.49], p=.015).Conclusions: In a depressed population, higher vitamin D levels were associated with lower prevalence and incidence of frailty. Future studies should examine whether the favorable effect of low vitamin D levels on the course of frailty can be explained by confounding or whether unknown pathophysiological mechanisms may exert protective effects.

Frailty and Somatic Comorbidity in Older Patients With Medically Unexplained Symptoms.

OBJECTIVES: To examine the level of frailty and somatic comorbidity in older patients with medically unexplained symptoms (MUS) and compare this to patients with medically explained symptoms (MES). DESIGN: Cross-sectional, comparative study. SETTING: Community, primary care, and secondary healthcare to recruit patients with MUS in various developmental and severity stages and primary care to recruit patients with MES. PARTICIPANTS: In total, 118 patients with MUS and 154 patients with MES, all aged ≥60 years. METHODS: Frailty was assessed according to the Fried criteria (gait speed, handgrip strength, unintentional weight loss, exhaustion, and low physical activity), somatic comorbidity according to the self-report Charlson comorbidity index, and the number of prescribed medications. RESULTS: Although patients with MUS had less physical comorbidity compared with patients with MES, they were prescribed the same number of medications. Moreover, patients with MUS were more often frail compared with patients with MES. Among patients with MUS, physical frailty was associated with the severity of unexplained symptoms, the level of hypochondriacal beliefs, and the level of somatisation. CONCLUSIONS AND IMPLICATIONS: Despite a lower prevalence of overt somatic diseases, patients with MUS are more frail compared with older patients with MES. These results suggest that at least in some patients age-related phenomena might be erroneously classified as MUS, which may affect treatment strategy.

Leucocyte telomere length is no molecular marker of physical frailty in late-life depression.

BACKGROUND: Although average life-expectancy is still increasing worldwide, ageing processes markedly differ between individuals, which has stimulated the search for biomarkers of biological ageing. OBJECTIVES: Firstly, to explore the cross-sectional and longitudinal association between leucocyte telomere length (LTL) as molecular marker of ageing and the physical frailty phenotype (PFP) as a clinical marker of ageing and secondly, to examine whether these associations are moderated by the presence of a depressive disorder, as depression can be considered a condition of accelerated ageing. METHODS: Among 378 depressed older patients (according to DSM-IV criteria) and 132 non-depressed older persons participating in the Netherlands Study of Depression in Older persons, we have assessed the physical frailty phenotype and LTL. The PFP was defined according to Fried's criteria and its components were reassessed at two-year follow-up. RESULTS: LTL was neither associated with the PFP at baseline by Spearman rank correlation tests, nor did it predict change in frailty parameters over a two-year follow-up using regression analyses adjusted for potential confounders. CONCLUSION: LTL is not associated with frailty; neither in non-depressed nor in depressed older persons. As LTL and physical frailty appear to represent different aspects of ageing, they may complement each other in future studies.

Physical Frailty and Cognitive Functioning in Depressed Older Adults: Findings From the NESDO Study.

OBJECTIVES: Cognitive frailty has recently been defined as the co-occurrence of physical frailty and cognitive impairment. Late-life depression is associated with both physical frailty and cognitive impairment, especially processing speed and executive functioning. The objective of this study was to investigate the association between physical frailty and cognitive functioning in depressed older persons. DESIGN: Baseline data of a depressed cohort, participating in the Netherlands Study of Depression in Older persons (NESDO). SETTING: Primary care and specialized mental health care. PARTICIPANTS: A total of 378 patients (≥60 years) with depression according to DSM-IV criteria and a MMSE score of 24 points or higher. MEASUREMENTS: The physical frailty phenotype as well as its individual criteria (weight loss, weakness, exhaustion, slowness, low activity). Cognitive functioning was examined in 4 domains: verbal memory, working memory, interference control, and processing speed. RESULTS: Of the 378 depressed patients (range 60-90 years; 66.1% women), 61 were classified as robust (no frailty criteria present), 214 as prefrail (1 or 2 frailty criteria present), and 103 as frail (≥3 criteria). Linear regression analyses, adjusted for confounders, showed that the severity of physical frailty was associated with poorer verbal memory (ß = -0.13, P = .039), slower processing speed (ß = -0.20, P = .001), and decreased working memory (ß = -0.18, P = .004), but not with changes in interference control (ß = 0.04, P = .54). CONCLUSION: In late-life depression, physical frailty is associated with poorer cognitive functioning, although not consistently for executive functioning. Future studies should examine whether cognitive impairment in the presence of physical frailty belongs to cognitive frailty and is indeed an important concept to identify a specific subgroup of depressed older patients, who need multimodal treatment strategies integrating physical, cognitive, and psychological functioning.

Relationship Between Physical Frailty and Low-Grade Inflammation in Late-Life Depression.

OBJECTIVES: To determine whether physical frailty is associated with low-grade inflammation in older adults with depression, because late-life depression is associated with physical frailty and low-grade inflammation. DESIGN: Baseline data of a cohort study. SETTING: Primary care and specialized mental health care. PARTICIPANTS: Individuals aged 60 and older with depression according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria (N = 366). MEASUREMENTS: The physical frailty phenotype, defined as three out of five criteria (weight loss, weakness, exhaustion, slowness, low physical activity level), and three inflammatory markers (C-reactive protein (CRP), interleukin-6 (IL-6), and neutrophil gelatinase-associated lipocalin (NGAL)) were assessed. RESULTS: The physical frailty phenotype was not associated with inflammatory markers in linear regression models adjusted for sociodemographic characteristics, lifestyle characteristics, and somatic morbidity. Of the individual criteria, handgrip strength was associated with CRP (ß = -0.21, P = .002) and IL-6 (ß = -0.25, P < .001), and gait speed was associated with NGAL (ß = 0.15, P = .02). Principal component analysis identified two dimensions within the physical frailty phenotype: performance-based physical frailty (encompassing gait speed, handgrip strength, and low physical activity) and vitality-based physical frailty (encompassing weight loss and exhaustion). Only performance-based physical frailty was associated with higher levels of inflammatory markers (CRP: ß = 0.14, P = .03; IL-6: ß = 0.13, P = .06; NGAL: ß = 0.14, P = .03). CONCLUSION: The physical frailty phenotype is not a unidimensional construct in individuals with depression. Only performance-based physical frailty is associated with low-grade inflammation in late-life depression, which might point to a specific depressive subtype.

The role of frailty in the association between depression and somatic comorbidity: results from baseline data of an ongoing prospective cohort study.

BACKGROUND: Depression and physical frailty in older persons are both associated with somatic diseases, but are hardly examined in concert. OBJECTIVES: To examine whether depression and physical frailty act independently and/or synergistically in their association with somatic diseases. DESIGN: Baseline data of an ongoing observational cohort study including depressed cases and non-depressed comparison subjects. SETTINGS: Netherlands Study of Depression in Older persons (NESDO). PARTICIPANTS: 378 depressed older persons confirmed by the Composite International Diagnostic Interview (CIDI), version 2.1, and 132 non-depressed comparison subjects. METHODS: Multiple linear regression analyses adjusted for socio-demographic and life-style characteristics were conducted with the number of somatic diseases as the dependent variable and depression and physical frailty as independent variables. Physical frailty was defined as ≥3 of the following characteristics, slowness, low physical activity, weight loss, exhaustion, and weakness. RESULTS: Depression and physical frailty did not interact in explaining variance in the number of somatic diseases (p=.57). Physical frailty, however, partly mediated the association between depression and somatic diseases, as the strength of this association decreased by over 10% when frailty was added to the model (B=0.47, p=.003, versus B=0.41, p=.01). The mediation effect was primarily driven by the frailty criterion exhaustion. Of the remaining frailty components, only slowness was associated with the number of somatic diseases; but this association was fully independent of depression. CONCLUSIONS: Our results suggest that depression and physical frailty have common pathways towards somatic diseases, as well as unique pathways. As no high-risk group was identified (no significant interaction), mental health nurses should regularly monitor for physical frailty within their caseload of depressed patients.

Flemish adolescents' perceptions of cigarette plain packaging: a qualitative study with focus group discussions.

OBJECTIVES: To find out whether there is a potential impact of the appearance of a plain cigarette package on the smoking perceptions and behavioural intentions of Flemish adolescents. DESIGN: We performed a cross-sectional study using the qualitative method of focus group discussions. SETTING: Flemish adolescents. PARTICIPANTS: We performed eight focus group discussions, in which 55 adolescents took part, 32 female and 23 male. Inclusion criteria were: Flemish male and female 15-year-olds to 16-year-olds and 17-year-olds to 18-year-olds attending regular high-school education or vocational training who were current or had ever been smokers. OUTCOME MEASURE (PLANNED AS WELL AS MEASURED): The opinions and perceptions of young Flemish smokers regarding the impact of cigarette packaging on their smoking behaviour. RESULTS: Plain packages are perceived as less attractive, cheap and unreliable for young people. Because of the unattractiveness of the plain packaging, the health warnings catch the eye much more strongly. CONCLUSIONS: In this first scientific study in Flanders on this topic, it emerged that plain packaging could be a strong policy tool to reduce the number of adolescents starting smoking. Validation of these findings by conducting a quantitative survey in the same target group is recommended.