Anticholinergic drugs and negative outcomes in the older population: from biological plausibility to clinical evidence.

The use of medication with anticholinergic properties is widespread among older subjects. Many drugs of common use such as antispasmodics, bronchodilators, antiarrhythmics, antihistamines, anti-hypertensive drugs, antiparkinson agents, skeletal muscle relaxants, and psychotropic drugs have been demonstrated to have an anticholinergic activity. The most frequent adverse effects are dry mouth, nausea, vomiting, constipation, abdominal pain, urinary retention, blurred vision, tachycardia and neurologic impairment such as confusion, agitation and coma. A growing evidence from experimental studies and clinical observations suggests that drugs with anticholinergic properties can cause physical and mental impairment in the elderly population. However, the morbidity and management issues associated with unwanted anticholinergic activity are underestimated and frequently overlooked. Moreover, their possible relation with specific negative outcome in the elderly population is still not firmly established. The aim of the present review was to evaluate the relationship between the use of drugs with anticholinergic activity and negative outcomes in older persons. We searched PubMed and Cochrane combining the search terms "anticholinergic", "delirium", "cognitive impairment", "falls", "mortality" and "discontinuation". Medicines with anticholinergic properties may increase the risks of functional and cognitive decline, morbidity, institutionalization and mortality in older people. However, such evidences are still not conclusive probably due to possible confounding factors. In particular, more studies are needed to investigate the effects of discontinuation of drug with anticholinergic properties. Overall, minimizing anticholinergic burden should always be encouraged in clinical practice to improve short-term memory, confusion and delirium, quality of life and daily functioning.

Micronucleus frequency in peripheral blood lymphocytes and frailty status in elderly. A lack of association with clinical features.

Frailty is a condition of vulnerability that carries an increased risk of poor outcome in elder adults. Frail individuals show fatigue, weight loss, muscle weakness, and a reduced physical function, and are known to frequently experience disability, social isolation, and institutionalization. Identifying frail people is a critical step for geriatricians to provide timely geriatric care and, eventually, to improve the quality of life in elderly. The aim of the present study is to investigate the association between frailty status and micronucleus (MN) frequency, a known marker of genomic instability, in a sample of elder adults. Several clinical features were evaluated and their possible association with MN frequency was tested. Criteria proposed by Fried were used to identify frail subjects. Overall, 180 elder adults entered the study, 93 of them (51.7%) frail. No association between MN frequency and frailty status was found under the specific conditions tested in this study (mean ratio=1.06; 95% CI 0.96-1.18). The inclusion of MN frequency in the Fried's frailty scale minimally improved the classification of study subjects according to the multidimensional prognostic index (MPI). The presence of genomic instability in the ageing process and in most chronic diseases, demands further investigation on this issue.

Serum levels of C-terminal agrin fragment (CAF) are associated with sarcopenia in older hip fractured patients.

BACKGROUND: Serum concentrations of the C-terminal fragment of agrin (CAF), a component of the neuromuscular junction (NMJ), are elevated in older community-dwellers with sarcopenia. Whether CAF may be used as a marker for muscle wasting in the presence of NMJ mechanical damage is presently unknown. The present study was undertaken to verify if serum CAF levels were associated with sarcopenia in older hip fractured patients. METHODS: Analyses were conducted in older adults hospitalized for traumatic hip fracture. The presence of sarcopenia was established according to the European Working Group on Sarcopenia in Older People criteria, with bioelectrical impedance analysis used for muscle mass estimation. Serum levels of CAF were determined using a commercial ELISA kit. RESULTS: Among 42 hip fractured patients (age 83.7±8.6 years, 76.2% women), sarcopenia was diagnosed in 7 individuals (16.7%). Serum CAF levels were significantly higher in sarcopenic relative to non-sarcopenic patients (172.2±47.5 pM vs. 93.1±44.0 pM; p<0.001). The association remained significant in both genders after adjustment for several potential confounders. CONCLUSION: Elevated serum CAF concentrations are associated with sarcopenia in older adults with hip fracture. The determination of serum CAF levels could therefore serve to identify a subset of hip fractured patients at especially high risk for adverse health outcomes.

Shorter telomeres in peripheral blood mononuclear cells from older persons with sarcopenia: results from an exploratory study.

BACKGROUND: Telomere shortening in peripheral blood mononuclear cells (PBMCs) has been associated with biological age and several chronic degenerative diseases. However, the relationship between telomere length and sarcopenia, a hallmark of the aging process, is unknown. The aim of the present study was therefore to determine whether PBMC telomeres obtained from sarcopenic older persons were shorter relative to non-sarcopenic peers. We further explored if PBMC telomere length was associated with frailty, a major clinical correlate of sarcopenia. METHODS: Analyses were conducted in 142 persons aged ≥65 years referred to a geriatric outpatient clinic (University Hospital). The presence of sarcopenia was established according to the European Working Group on Sarcopenia in Older People criteria, with bioelectrical impedance analysis used for muscle mass estimation. The frailty status was determined by both the Fried's criteria (physical frailty, PF) and a modified Rockwood's frailty index (FI). Telomere length was measured in PBMCs by quantitative real-time polymerase chain reaction according to the telomere/single-copy gene ratio (T/S) method. RESULTS: Among 142 outpatients (mean age 75.0 ± 6.5 years, 59.2% women), sarcopenia was diagnosed in 23 individuals (19.3%). The PF phenotype was detected in 74 participants (52.1%). The average FI score was 0.46 ± 0.17. PBMC telomeres were shorter in sarcopenic subjects (T/S = 0.21; 95% CI: 0.18-0.24) relative to non-sarcopenic individuals (T/S = 0.26; 95% CI: 0.24-0.28; p = 0.01), independent of age, gender, smoking habit, or comorbidity. No significant associations were determined between telomere length and either PF or the FI. CONCLUSION: PBMC telomere length, expressed as T/S values, is shorter in older outpatients with sarcopenia. The cross-sectional assessment of PBMC telomere length is not sufficient at capturing the complex, multidimensional syndrome of frailty.