The 'Vascular Depression' hypothesis posits that cerebrovascular disease may predispose, precipitate or perpetuate some geriatric depressive syndromes. This hypothesis stimulated much research that has improved our understanding of the complex relationships between late-life depression (LLD), vascular risk factors, and cognition. Succinctly, there are well-established relationships between LLD, vascular risk factors and cerebral hyperintensities, the radiological hallmark of vascular depression. Cognitive dysfunction is common in LLD, particularly executive dysfunction, a finding predictive of poor antidepressant response. Over time, progression of hyperintensities and cognitive deficits predicts a poor course of depression and may reflect underlying worsening of vascular disease. This work laid the foundation for examining the mechanisms by which vascular disease influences brain circuits and influences the development and course of depression. We review data testing the vascular depression hypothesis with a focus on identifying potential underlying vascular mechanisms. We propose a disconnection hypothesis, wherein focal vascular damage and white matter lesion location is a crucial factor, influencing neural connectivity that contributes to clinical symptomatology. We also propose inflammatory and hypoperfusion hypotheses, concepts that link underlying vascular processes with adverse effects on brain function that influence the development of depression. Testing such hypotheses will not only inform the relationship between vascular disease and depression, but also provide guidance on the potential repurposing of pharmacological agents that may improve LLD outcomes.

The vascular depression hypothesis: mechanisms linking vascular disease with depression.

Objective 
The purpose of this study was to perform a systematic review to assess the short-, middle- and long-term consequences of sarcopenia.


Methods 
Prospective studies assessing the consequences of sarcopenia were searched across different electronic databases (MEDLINE, EMBASE, EBM Reviews, Cochrane Database of Systematic Reviews, EBM Reviews ACP Journal Club, EBM Reviews DARE and AMED). Only studies that used the definition of the European Working Group on Sarcopenia in Older People to diagnose sarcopenia were included. Study selection and data extraction were performed by two independent reviewers. For outcomes reported by three or more studies, a meta-analysis was performed. The study results are expressed as odds ratios (OR) with 95% CI.


Results 
Of the 772 references identified through the database search, 17 were included in this systematic review. The number of participants in the included studies ranged from 99 to 6658, and the duration of follow-up varied from 3 months to 9.8 years. Eleven out of 12 studies assessed the impact of sarcopenia on mortality. The results showed a higher rate of mortality among sarcopenic subjects (pooled OR of 3.596 (95% CI 2.96–4.37)). The effect was higher in people aged 79 years or older compared with younger subjects (p = 0.02). Sarcopenia is also associated with functional decline (pooled OR of 6 studies 3.03 (95% CI 1.80–5.12)), a higher rate of falls (2/2 studies found a significant association) and a higher incidence of hospitalizations (1/1 study). The impact of sarcopenia on the incidence of fractures and the length of hospital stay was less clear (only 1/2 studies showed an association for both outcomes).


Conclusion 
Sarcopenia is associated with several harmful outcomes, making this geriatric syndrome a real public health burden.

/pdf/health-outcomes-of-sarcopenia-a-systematic-review-and-meta-3ce12km1iq.pdf

Health Outcomes of Sarcopenia: A Systematic Review and Meta-Analysis.

Sarcopenia, defined as an age-associated loss of skeletal muscle function and muscle mass, occurs in approximately 6 - 22 % of older adults. This paper presents evidence-based clinical practice guidelines for screening, diagnosis and management of sarcopenia from the task force of the International Conference on Sarcopenia and Frailty Research (ICSFR). To develop the guidelines, we drew upon the best available evidence from two systematic reviews paired with consensus statements by international working groups on sarcopenia. Eight topics were selected for the recommendations: (i) defining sarcopenia; (ii) screening and diagnosis; (iii) physical activity prescription; (iv) protein supplementation; (v) vitamin D supplementation; (vi) anabolic hormone prescription; (vii) medications under development; and (viii) research. The ICSFR task force evaluated the evidence behind each topic including the quality of evidence, the benefitharm balance of treatment, patient preferences/values, and cost-effectiveness. Recommendations were graded as either strong or conditional (weak) as per the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Consensus was achieved via one face-to-face workshop and a modified Delphi process. We make a conditional recommendation for the use of an internationally accepted measurement tool for the diagnosis of sarcopenia including the EWGSOP and FNIH definitions, and advocate for rapid screening using gait speed or the SARC-F. To treat sarcopenia, we strongly recommend the prescription of resistance-based physical activity, and conditionally recommend protein supplementation/a protein-rich diet. No recommendation is given for Vitamin D supplementation or for anabolic hormone prescription. There is a lack of robust evidence to assess the strength of other treatment options.

International Clinical Practice Guidelines for Sarcopenia (ICFSR): Screening, Diagnosis and Management

Selective serotonin and serotonin norepinephrine reuptake inhibitors (SSRI; SNRI) are the first choice pharmacological treatment options for major depression. It has long been assumed that the primary therapeutic mechanism of action of these drugs involves the modulation of monoaminergic systems. However, contemporary investigations have revealed that depression is linked with inflammation, and that SSRI/SNRIs possess significant anti-inflammatory actions. While these anti-inflammatory properties initially only related to work undertaken on cells of the peripheral immune system, it has recently become apparent that these drugs also exert anti-inflammatory effects on microglia, the principal cells within the CNS that regulate and respond to inflammatory factors. The aim of the current study was to compare SSRI/SNRIs in terms of their anti-inflammatory potency, and to determine the specific mechanisms through which these effects are mediated. Accordingly, the current study evaluated the ability of five different SSRIs (fluoxetine, sertraline, paroxetine, fluvoxamine and citalopram) and one SNRI (venlafaxine) to suppress microglial responses to an inflammatory stimulus. Specifically, we examined their ability to alter tumour necrosis factor-α (TNF-α) and nitric oxide (NO) production after 4 and 24 h stimulation with lipopolysaccharide. Our results indicated that the SSRIs potently inhibited microglial TNF-α and NO production. We then investigated whether these effects might involve either β-adrenoceptor or cAMP signalling. Using the protein kinase A inhibitor Rp-CAMPs, we found evidence to suggest that cAMP signalling is involved in regulating the anti-inflammatory response. These findings suggest that antidepressants may owe at least some of their therapeutic effectiveness to their anti-inflammatory properties.

A comparative examination of the anti-inflammatory effects of SSRI and SNRI antidepressants on LPS stimulated microglia

Objective The purpose of this study was to perform a systematic review to assess the short-, middle- and long-term consequences of sarcopenia. Methods Prospective studies assessing the consequences of sarcopenia were searched across different electronic databases (MEDLINE, EMBASE, EBM Reviews, Cochrane Database of Systematic Reviews, EBM Reviews ACP Journal Club, EBM Reviews DARE and AMED). Only studies that used the definition of the European Working Group on Sarcopenia in Older People to diagnose sarcopenia were included. Study selection and data extraction were performed by two independent reviewers. For outcomes reported by three or more studies, a meta-analysis was performed. The study results are expressed as odds ratios (OR) with 95% CI. Results Of the 772 references identified through the database search, 17 were included in this systematic review. The number of participants in the included studies ranged from 99 to 6658, and the duration of follow-up varied from 3 months to 9.8 years. Eleven out of 12 studies assessed the impact of sarcopenia on mortality. The results showed a higher rate of mortality among sarcopenic subjects (pooled OR of 3.596 (95% CI 2.96–4.37)). The effect was higher in people aged 79 years or older compared with younger subjects (p = 0.02). Sarcopenia is also associated with functional decline (pooled OR of 6 studies 3.03 (95% CI 1.80–5.12)), a higher rate of falls (2/2 studies found a significant association) and a higher incidence of hospitalizations (1/1 study). The impact of sarcopenia on the incidence of fractures and the length of hospital stay was less clear (only 1/2 studies showed an association for both outcomes). Conclusion Sarcopenia is associated with several harmful outcomes, making this geriatric syndrome a real public health burden.

Health outcomes of sarcopenia: a systematic review and meta-analysis.

Sarcopenia and malnutrition in acutely ill hospitalized elderly: Prevalence and outcomes.

Objective

The immune system (IS) plays a key role in the mechanisms underlying major depression (MD) and pro-inflammatory cytokines seem to be particularly involved in the pathogenesis of the disease. There is growing evidence of a relationship between commonly studied single nucleotide polymorphisms (SNPs) in cytokine genes and an increased risk of MD.



The aim of our study was to investigate the association between the −308(G/A) SNP in the tumour necrosis factor-α (TNF-α) gene and late-life MD in elderly people without dementia.



Methods

Blood samples were obtained from 50 subjects enrolled at the Geriatric Department of the San Gerardo Hospital in Monza, Italy, after screening with the geriatric depression scale (GDS ≥ 15) and mini-mental state evaluation (MMSE ≥ 24). The −308 (G/A) SNP was genotyped by SSP-PCR amplification. Two hundred and forty age-matched healthy volunteers were taken as the control group.



Results

Genotype and allele distributions in patients with MD were significantly different from those of the controls. In subjects affected by MD we found a higher percentage of the GG genotype (84 vs. 68,3%; p = 0.007) and thus of the G allele (92 vs. 81,9%; p = 0.05).



The GG genotype was associated with a greater risk of developing the disease (OR 2.433, CI 1.09–5.43).



Conclusions

Our study suggests that the −308 (G/A) polymorphism in the TNF-α gene could play a role in determining susceptibility to MD. An activation of the TNF-α system could contribute to the development of MD in the elderly. Copyright © 2009 John Wiley & Sons, Ltd.

The -308 (G/A) single nucleotide polymorphism in the TNF-α gene and the risk of major depression in the elderly

-308(G/A) TNF-α GENE POLYMORPHISM AND RISK OF DEPRESSION LATE IN THE LIFE

Takotsubo cardiomyopathy in an elderly patient with severe Alzheimer's disease: a case report.

Early diagnosis of infections is often a challenge in older patients, since this age group may have atypical presentation. We report here the cases of 3 old patients, in whom a sudden decline in mobility status occurred shortly before the onset of the classically recognized features of infection. The decline was interpreted as an anticipatory marker of imminent infection. We discuss the possible implications of our findings and the opportunity that they offer to improve routine clinical practice in older patients.

Anna Paola Cerri

Papers

Sarcopenia and malnutrition in acutely ill hospitalized elderly: Prevalence and outcomes.

The -308 (G/A) single nucleotide polymorphism in the TNF-α gene and the risk of major depression in the elderly

-308(G/A) TNF-α GENE POLYMORPHISM AND RISK OF DEPRESSION LATE IN THE LIFE

Takotsubo cardiomyopathy in an elderly patient with severe Alzheimer's disease: a case report.

A sudden decline in mobility status as an early sign of acute infection in elderly patients: evidence from three case reports.