The body of evidence of late-life depression: the complex relationship between depressive symptoms, movement, dyspnea and cognition.

BACKGROUND: Physical symptoms play an important role in late-life depression and may contribute to residual symptomatology after antidepressant treatment. In this exploratory study, we examined the role of specific bodily dimensions including movement, respiratory functions, fear of falling, cognition, and physical weakness in older people with depression. METHODS: Clinically stable older patients with major depression within a Psychiatric Consultation-Liaison program for Primary Care underwent comprehensive assessment of depressive symptoms, instrumental movement analysis, dyspnea, weakness, activity limitations, cognitive function, and fear of falling. Network analysis was performed to explore the unique adjusted associations between clinical dimensions. RESULTS: Sadness was associated with worse turning and walking ability and movement transitions from walking to sitting, as well as with worse general cognitive abilities. Sadness was also connected with dyspnea, while neurovegetative depressive burden was connected with activity limitations. DISCUSSION: Limitations of motor and cognitive function, dyspnea, and weakness may contribute to the persistence of residual symptoms of late-life depression.

Correction to: Nutraceutical approach for the management of cardiovascular risk - a combination containing the probiotic Bifidobacterium longum BB536 and red yeast rice extract: results from a randomized, double-blind, placebo-controlled study.

Following publication of the original article [1], the authors reported an error in the affiliation of the third author, Sara Gandini. The correct affiliation should read: Division of Epidemiology and Biostatistics, IEO, European Institute of Oncology IRCCS, Milan, Italy.

Nutraceutical approach for the management of cardiovascular risk - a combination containing the probiotic Bifidobacterium longum BB536 and red yeast rice extract: results from a randomized, double-blind, placebo-controlled study.

BACKGROUND: Probiotics incorporated into dairy products have been shown to reduce total (TC) and LDL cholesterolemia (LDL-C) in subjects with moderate hypercholesterolemia. More specifically, probiotics with high biliary salt hydrolase activity, e.g. Bifidobacterium longum BB536, may decrease TC and LDL-C by lowering intestinal cholesterol reabsorption and, combined with other nutraceuticals, may be useful to manage hypercholesterolemia in subjects with low cardiovascular (CV) risk. This study was conducted to evaluate the efficacy and safety of a nutraceutical combination containing Bifidobacterium longum BB536, red yeast rice (RYR) extract (10 mg/day monacolin K), niacin, coenzyme Q10 (Lactoflorene Colesterolo®). The end-points were changes of lipid CV risk markers (LDL-C, TC, non-HDL-cholesterol (HDL-C), triglycerides (TG), apolipoprotein B (ApoB), HDL-C, apolipoprotein AI (ApoAI), lipoprotein(a) (Lp(a), proprotein convertase subtilisin/kexin type 9 (PCSK9)), and of markers of cholesterol synthesis/absorption. METHODS: A 12-week randomized, parallel, double-blind, placebo-controlled study. Thirty-three subjects (18-70 years) in primary CV prevention and low CV risk (SCORE: 0-1% in 24 and 2-4% in 9 subjects; LDL-C: 130-200 mg/dL) were randomly allocated to either nutraceutical (N = 16) or placebo (N = 17). RESULTS: Twelve-week treatment with the nutraceutical combination, compared to placebo, significantly reduced TC (- 16.7%), LDL-C (- 25.7%), non-HDL-C (- 24%) (all p < 0.0001), apoB (- 17%, p = 0.003). TG, HDL-C, apoAI, Lp(a), PCSK9 were unchanged. Lathosterol:TC ratio was significantly reduced by the nutraceutical combination, while campesterol:TC ratio and sitosterol:TC ratio did not change, suggesting reduction of synthesis without increased absorption of cholesterol. No adverse effects and a 97% compliance were observed. CONCLUSIONS: A 12-week treatment with a nutraceutical combination containing the probiotic Bifidobacterium longum BB536 and RYR extract significantly improved the atherogenic lipid profile and was well tolerated by low CV risk subjects. TRIAL REGISTRATION: NCT02689934 .

Omega-3 Fatty Acids and Neurodegenerative Diseases: New Evidence in Clinical Trials.

A nutritional approach could be a promising strategy to prevent or slow the progression of neurodegenerative diseases such as Parkinson's and Alzheimer's disease, since there is no effective therapy for these diseases so far. The beneficial effects of omega-3 fatty acids are now well established by a plethora of studies through their involvement in multiple biochemical functions, including synthesis of anti-inflammatory mediators, cell membrane fluidity, intracellular signaling, and gene expression. This systematic review will consider epidemiological studies and clinical trials that assessed the impact of supplementation or dietary intake of omega-3 polyunsaturated fatty acids on neurodegenerative diseases such as Parkinson's and Alzheimer's diseases. Indeed, treatment with omega-3 fatty acids, being safe and well tolerated, represents a valuable and biologically plausible tool in the management of neurodegenerative diseases in their early stages.

Physical exercise for late life depression: effects on cognition and disability.

BACKGROUND: Late-life depression is often associated with cognitive impairments and disability, which may persist even after adequate antidepressant drug treatment. Physical exercise is increasingly recognized as an effective antidepressant agent, and may exert positive effects on these features too. However, few studies examined this issue, especially by comparing different types of exercises. METHODS: We performed secondary analyses on data from the Safety and Efficacy of Exercise for Depression in Seniors study, a trial comparing the antidepressant effectiveness of sertraline (S), sertraline plus thrice-weekly non-progressive exercise (S+NPE), and sertraline plus thrice-weekly progressive aerobic exercise (S+PAE). Exercise was conducted in small groups and monitored by heart rate meters. Patients with late-life depression without severe cognitive impairment were recruited from primary care and assessed at baseline and 24 weeks, using the Montreal Cognitive Assessment (MOCA, total and subdomain scores) and Brief Disability Questionnaire. Analyses were based on Generalized Linear Models. RESULTS: In total, 121 patients (mean age 75, 71% females) were randomized to the study interventions. Compared with the S group, patients in the S+PAE group displayed greater improvements of MOCA total scores (p=0.006, effect size=0.37), visuospatial/executive functions (p=0.001, effect size=0.13), and disability (p=0.02, effect size=-0.31). Participants in the S+NPE group did not display significant differences with the control group. CONCLUSIONS: Adding aerobic, progressive exercise to antidepressant drug treatment may offer significant advantages over standard treatment for cognitive abilities and disability. These findings suggest that even among older patients exercise may constitute a valid therapeutic measure to improve patients' outcomes.

Risk of birth defects associated with maternal pregestational diabetes.

Maternal diabetes preceding pregnancy may increase the risk of birth defects in the offspring, but not all studies confirm this association, which has shown considerable variation over time, and the effect of having type 1 versus type 2 diabetes is unclear. We conducted a population-based cohort study in the Northern Italy Emilia-Romagna region linking administrative databases with a Birth Defects Registry. From hospital discharge records we identified all diabetic pregnancies during 1997-2010, and a population of non-diabetic parturients matched for age, residence, year and delivery hospital. We collected available information on education, smoking and drug prescriptions, from which we inferred the type of diabetes. We found 62 malformed infants out of 2,269 births among diabetic women, and 162 out of 10,648 births among non-diabetic women. The age-standardized prevalence ratio (PR) of malformation associated with maternal pregestational diabetes was 1.79 (95 % confidence interval 1.34-2.39), a value that varied little by age. Type of diabetes strongly influenced the PR, with higher values related to type 2 diabetic women. Most major subgroups of anomalies had PRs above 1, including cardiovascular, genitourinary, musculoskeletal, and chromosomal abnormalities. There was an unusually high PR for the rare defect 'extra-ribs', but it was based on only two cases. This study indicates that maternal pregestational type 2 diabetes is associated with a higher prevalence of specific birth defects in offspring, whereas for type 1 diabetic mothers, particularly in recent years, the association was unremarkable.

Intrarenal Venous Doppler as a novel marker for optimal decongestion, patient management, and prognosis in Acute Decompensated Heart Failure.

AIMS: An increase in right atrial pressure is a common feature of acute decompensated heart failure (ADHF). Such increased pressure leads to persistent kidney congestion. A marker to guide optimal diuretic therapy is missing. We aim to correlate intrarenal Doppler (IRD) ultrasound in ADHF patients with clinical outcomes to assess whether renal haemodynamic parameter changes are useful for monitoring kidney congestion. METHODS AND RESULTS: Between December 2018 and January 2020, ADHF patients requiring intravenous diuretic therapy for at least 48 h were considered for study selection. An IRD blinded examination was performed on Days 1, 3, and 5, and clinical and laboratory parameters were recorded. Venous Doppler profiles (VDP) were classified as continuous (C), pulsatile (P), biphasic (B), or monophasic (M) according to the congestion degree; B and M profiles were considered deranged. A VDP improvement (VDPimp) was defined as a change of ≥1 pattern degree or maintenance of C or P patterns. An arterial resistive index (RI) > 0.8 was considered elevated. Outcomes of death and rehospitalization were gathered at 60 days. Data were assessed by regression and Kaplan-Meier analyses. All 177 ADHF patients admitted were screened, and 72 were enrolled [27 females-median age 81 (76-87) years-median ejection fraction 40% (30-52)]. The VDP derangement decreased from 79.2% on Day 1 to 51.4% on Day 5 (P < 0.05). The RI elevation decreased from 60.6% on Day 1 to 43.1% on Day 5 (P < 0.05). At Day 5, VDPimp was registered in over half of the patients (59.7%). At Day 5, signs of congestion (dyspnoea/oedema/rales), fluid accumulation (pleural/peritoneal fluid), haematocrit, and brain natriuretic peptide improved (P > 0.05). After 60 days, 12 (16.7%) patients were readmitted and 9 (12.5%) died. The VDPimp was identified as the unique independent factor associated with readmission [Hazard Ratio (HR) 0.22, 95% (confidence interval) CI 0.05-0.94, P = 0.04] and death (HR 0.07, 95% CI 0.01-0.68, P = 0.02), with significantly better outcomes identified in VDPimp patients (log-rank test, P < 0.05). CONCLUSION: Decongestion may be associated with improvements in many clinical and instrumental parameters, but only VDPimp was associated with better clinical outcomes. The VDPimp should be incorporated in ad hoc ADHF clinical trials to better define its role in everyday practice.

The use of stable and radioactive sterol tracers as a tool to investigate cholesterol degradation to bile acids in humans in vivo.

Alterations of cholesterol homeostasis represent important risk factors for atherosclerosis and cardiovascular disease. Different clinical-experimental approaches have been devised to study the metabolism of cholesterol and particularly the synthesis of bile acids, its main catabolic products. Most evidence in humans has derived from studies utilizing the administration of labeled sterols; these have several advantages over in vitro assay of enzyme activity and expression, requiring an invasive procedure such as a liver biopsy, or the determination of fecal sterols, which is cumbersome and not commonly available. Pioneering evidence with administration of radioactive sterol derivatives has allowed to characterize the alterations of cholesterol metabolism and degradation in different situations, including spontaneous disease conditions, aging, and drug treatment. Along with the classical isotope dilution methodology, other approaches were proposed, among which isotope release following radioactive substrate administration. More recently, stable isotope studies have allowed to overcome radioactivity exposure. Isotope enrichment studies during tracer infusion has allowed to characterize changes in the degradation of cholesterol via the "classical" and the "alternative" pathways of bile acid synthesis. Evidence brought by tracer studies in vivo, summarized here, provides an exceptional tool for the investigation of sterol metabolism, and integrate the studies in vitro on human tissue.

MoCA 7.1: Multicenter Validation of the First Italian Version of Montreal Cognitive Assessment.

Background: The early detection of neurocognitive disorders, especially when mild, is a key issue of health care systems including the Italian Dementia National Plan. The Mini-Mental State Examination (MMSE), i.e., the reference screening tool for dementia in Italian Memory Clinics, has low sensitivity in detecting mild cognitive impairment (MCI) or mild dementia. Objective: Availability of a 10-minute screening test sensitive to MCI and mild dementia, such as the Montreal Cognitive Assessment (MoCA), is relevant in the field. This study presents initial validity and reliability data for the Italian version of MoCA 7.1 that is being collected as part of a large ongoing longitudinal study to evaluate the rate of incident MCI and dementia in older adults. Methods: MoCA 7.1 and MMSE were administered to cognitive impaired patients (n = 469; 214 with MCI, 255 with dementia; mean age: 75.5; 52% females,) and healthy older adults (n = 123, mean age: 69.7, 64 % females). Results: Test-retest (0.945, p < 0.001) and inter-rater (0.999, p < 0.001) reliability of MoCA 7.1, assessed on randomly selected participants with normal cognition, MCI, dementia, were significant. MoCA 7.1 showed adequate sensitivity (95.3%) and specificity (84.5%) in detecting MCI compared to MMSE (sensitivity: 53.8%; specificity: 87.5%). The Area Under the Curve of MoCA 7.1 was significantly greater than that of MMSE (0.963 versus 0.742). MoCA 7.1 showed similar results in detecting both MCI and dementia. Conclusion: MoCA 7.1 is a reliable and useful tool that can aid in the diagnosis of MCI and dementia in the Italian population.

Efficacy of a multiple-component and multifactorial personalized fall prevention program in a mixed population of community-dwelling older adults with stroke, Parkinson's Disease, or frailty compared to usual care: The PRE.C.I.S.A. randomized controlled trial.

Background: Fall risk in the elderly is a major public health issue due to the injury-related consequences and the risk of associated long-term disability. However, delivering preventive interventions in usual clinical practice still represents a challenge. Aim: To evaluate the efficacy of a multiple-component combined with a multifactorial personalized intervention in reducing fall rates in a mixed population of community-dwelling elderly compared to usual care. Design: Randomized Controlled Trial (NCT03592420, clinicalTrials.gov). Setting: Outpatients in two Italian centers. Population: 403 community-dwelling elderly at moderate-to-high fall risk, including subjects with Parkinson's Disease and stroke. Methods: After the randomization, the described interventions were administered to the intervention group (n = 203). The control group (n = 200) received usual care and recommendations to minimize fall risk factors. In addition, each participant received a fall diary, followed by 12 monthly phone calls. The primary endpoint was the total number of falls in each group over 12 months, while the secondary endpoints were other fall-related indicators recorded at one year. In addition, participants' functioning was assessed at baseline (T1) and 3-month (T3). Results: 690 falls were reported at 12 months, 48.8% in the intervention and 51.2% in the control group, with 1.66 (± 3.5) and 1.77 (± 3.2) mean falls per subject, respectively. Subjects with ≥ 1 fall and ≥2 falls were, respectively, 236 (58.6%) and 148 (36.7%). No statistically significant differences were observed between groups regarding the number of falls, the falling probability, and the time to the first fall. According to the subgroup analysis, no significant differences were reported. However, a statistically significant difference was found for the Mini-BESTest (p = 0.004) and the Fullerton Advanced Balance Scale (p = 0.006) for the intervention group, with a small effect size (Cohen's d 0.26 and 0.32, respectively), at T1 and T3 evaluations. Conclusions: The intervention was ineffective in reducing the number of falls, the falling probability, and the time to the first fall at 12 months in a mixed population of community-dwelling elderly. A significant improvement for two balance indicators was recorded in the intervention group. Future studies are needed to explore different effects of the proposed interventions to reduce falls and consequences.

Interactions of Oxysterols with Atherosclerosis Biomarkers in Subjects with Moderate Hypercholesterolemia and Effects of a Nutraceutical Combination (Bifidobacterium longum BB536, Red Yeast Rice Extract) (Randomized, Double-Blind, Placebo-Controlled Study).

BACKGROUND: Oxysterol relationship with cardiovascular (CV) risk factors is poorly explored, especially in moderately hypercholesterolaemic subjects. Moreover, the impact of nutraceuticals controlling hypercholesterolaemia on plasma levels of 24-, 25- and 27-hydroxycholesterol (24-OHC, 25-OHC, 27-OHC) is unknown. METHODS: Subjects (n = 33; 18-70 years) with moderate hypercholesterolaemia (low-density lipoprotein cholesterol (LDL-C:): 130-200 mg/dL), in primary CV prevention as well as low CV risk were studied cross-sectionally. Moreover, they were evaluated after treatment with a nutraceutical combination (Bifidobacterium longum BB536, red yeast rice extract (10 mg/dose monacolin K)), following a double-blind, randomized, placebo-controlled design. We evaluated 24-OHC, 25-OHC and 27-OHC levels by gas chromatography/mass spectrometry analysis. RESULTS: 24-OHC and 25-OHC were significantly correlated, 24-OHC was correlated with apoB. 27-OHC and 27-OHC/total cholesterol (TC) were higher in men (median 209 ng/mL and 77 ng/mg, respectively) vs. women (median 168 ng/mL and 56 ng/mg, respectively); 27-OHC/TC was significantly correlated with abdominal circumference, visceral fat and, negatively, with high-density lipoprotein cholesterol (HDL-C). Triglycerides were significantly correlated with 24-OHC, 25-OHC and 27-OHC and with 24-OHC/TC and 25-OHC/TC. After intervention, 27-OHC levels were significantly reduced by 10.4% in the nutraceutical group Levels of 24-OHC, 24-OHC/TC, 25-OHC, 25-OHC/TC and 27-OHC/TC were unchanged. CONCLUSIONS: In this study, conducted in moderate hypercholesterolemic subjects, we observed novel relationships between 24-OHC, 25-OHC and 27-OHC and CV risk biomarkers. In addition, no adverse changes of OHC levels upon nutraceutical treatment were found.

Use of Lipid-Lowering Drugs and Associated Outcomes According to Health State Profiles in Hospitalized Older Patients.

OBJECTIVE: To assess how lipid-lowering drugs (LLDs) are administered in the hospitalized patients aged 65 and older and their association with clinical outcomes according to their health-related profiles. DESIGN: This is a retrospective study based on data from REPOSI (REgistro POliterapie SIMI - Italian Society of Internal Medicine) register, an Italian network of internal medicine hospital wards. SETTING AND PARTICIPANTS: A total of 4642 patients with a mean age of 79 years enrolled between 2010 and 2018. METHODS: Socio-demographic characteristics, functional abilities, cognitive skills, laboratory parameters and comorbidities were used to investigate the health state profiles by using multiple correspondence analysis and clustering. Logistic regression was used to assess whether LLD prescription was associated with patients' health state profiles and with short-term mortality. RESULTS: Four clusters of patients were identified according to their health state: two of them (Cluster III and IV) were the epitome of frailty conditions with poor short-term outcomes, whereas the others included healthier patients. The average prevalence of LLD use was 27.6%. The lowest prevalence was found among the healthier patients in Cluster I and among the oldest frail patients with severe functional and cognitive impairment in Cluster IV. The highest prevalence was among multimorbid patients in Cluster III (OR=4.50, 95% CI=3.76-5.38) characterized by a high cardiovascular risk. Being prescribed with LLDs was associated with a lower 3-month mortality, even after adjusting for cluster assignment (OR=0.59; 95% CI = 0.44-0.80). CONCLUSION: The prevalence of LLD prescription was low and in overall agreement with guideline recommendations and with respect to patients' health state profiles.

Social engagement in late life may attenuate the burden of depressive symptoms due to financial strain in childhood.

BACKGROUND: It remains poorly understood if childhood financial strain is associated with old-age depression and if active social life may mitigate this relationship. AIMS: To investigate the association between childhood financial strain and depressive symptoms during aging; to examine whether late-life social engagement modifies this association. METHOD: 2884 dementia-free individuals (aged 60+) from the Swedish National study of Aging and Care-Kungsholmen were clinically examined over a 15-year follow-up. Presence of childhood financial strain was ascertained at baseline. Depressive symptoms were repeatedly assessed with the Montgomery-Åsberg Depression Rating Scale. Social engagement comprised information on baseline social network and leisure activities. Linear, logistic and mixed-effect models estimated baseline and longitudinal associations accounting for sociodemographic, clinical, and lifestyle factors. RESULTS: Childhood financial strain was independently associated with a higher baseline level of depressive symptoms (ß = 0.37, 95%CI 0.10-0.65), but not with symptom change over time. Relative to those without financial strain and with active social engagement, depressive burden was increased in those without financial strain but with inactive social engagement (ß = 0.43, 95%CI: 0.15-0.71), and in those with both financial strain and inactive engagement (ß = 0.99, 95%CI: 0.59-1.40). Individuals with financial strain and active social engagement exhibited similar depressive burden as those without financial strain and with active social engagement. LIMITATIONS: Recall bias and reverse causality may affect study results, although sensitivity analyses suggest their limited effect. CONCLUSIONS: Early-life financial strain may be of lasting importance for old-age depressive symptoms. Active social engagement in late-life may mitigate this association.

Instrumental assessment of balance and gait in depression: A systematic review.

Psychomotor symptoms of depression are understudied despite having a severe impact on patient outcomes. This review aims to summarize the evidence on motor features of depression assessed with instrumental procedures, and examine age-related differences. We included studies investigating posture, balance and gait ascertained with instrumental measurements among individuals with depressive symptoms or disorders. Studies on subjects with specific physical illnesses were excluded. Methodological quality was assessed with the Newcastle - Ottawa Scale (NOS) and PRISMA guidelines were followed. 33 studies (13 case-control, five cross-sectional, nine longitudinal and six intervention) with overall low-medium quality were included. Different instruments were employed to assess posture (e.g. digital cameras), balance (balance, stepping platform) or gait (e.g. Six-Minute-Walking Test, instrumented walkways). Results suggest that depression in adults is associated with significant impairments of posture, balance and gait. Motor abnormalities among depressed older adults may depend on the interplay of physical diseases, cognitive impairment and mood. Very few intervention studies measured motor symptoms as outcome. Available evidence suggests, however, that antidepressant drugs and physical exercise may be beneficial for motor abnormalities. Despite the lack of high-quality studies, instrumental assessments confirm the presence and importance of motor abnormalities in depression, with potential age-related differences in their pathophysiology.

Recommendations for Cardiovascular Prevention During the Sars-Cov-2 Pandemic: An Executive Document by the Board of the Italian Society of Cardiovascular Prevention.

In 2020, the Sars-Cov-2 pandemic is causing a huge and dramatic impact on healthcare systems worldwide. During this emergency, fragile patients suffering from other comorbidities, especially patients susceptible to or affected by cardiovascular disease, are the ones most exposed to the poorer outcomes. Therefore, it is still mandatory to continue to strictly adhere to the rules of cardiovascular prevention. This document aims to provide all doctors with simple and clear recommendations in order to spread useful messages to the widest number of subjects in order to continue the battle against cardiovascular diseases even in times of pandemic.