Processed meat consumption and the risk of incident late-onset depression: a 12-year follow-up of the Salus in Apulia Study.

BACKGROUND: the possible relationship between dietary habits and the incidence of late-onset depression (LOD), defined as first depression onset at later age, is unclear. OBJECTIVE: to investigate the relationship between consumption of different food groups and incident LOD. DESIGN: longitudinal population-based study with a 12-year follow-up. SETTING: Castellana Grotte, Bari, Italy. SUBJECTS: five hundred and forty-six older subjects from the Salus in Apulia Study. METHODS: baseline data were recorded in 2003-06, and diagnostic data were recorded in 2013-18 at follow-up. Dietary intake was assessed with a food frequency questionnaire. Depressive disorders were assessed with the Structured Clinical Interview for DSM-IV Axis I Disorders. Subjects who already suffered from depression or other psychiatric disorders at baseline were excluded from the analysis. The association between LOD and single dietary determinants was examined by Cox regression analysis and then applying the hazard ratio (HR). RESULTS: subjects with incident LOD (n = 34) had lower global cognition and total cholesterol levels and a higher body mass index (BMI) at baseline. Only processed meat significantly increased the risk of incident LOD of about 10% by 5 g/day intake (HR adjusted for age, sex, education, multimorbidity and BMI: 1.13, 95% confidence intervals: 1.04-1.22). A similar relationship was found for single foods in the processed meat food group such as sausages, salami and mortadella and baked ham, but not for raw ham. CONCLUSIONS: in midlife, a higher intake of processed meat was not only associated with an increased risk of cardiovascular- and metabolic-related chronic diseases in older age but also with an increased risk of developing LOD.

The diagnostic accuracy of late-life depression is influenced by subjective memory complaints and educational level in an older population in Southern Italy.

The prevalence of late-life depression (LLD) depends on the study sample, measurements, and diagnostic approaches. We estimated the 30 item-Geriatric Depression Scale (GDS-30) accuracy against the gold standard LLD diagnosis made with the Semi-structured Clinical Diagnostic Interview for DSM-IV-TR Axis I Disorders, focusing on the prevalence of a late-life major depressive disorder (MDD), in a population-based sample of 843 subjects aged>65 years, subdivided into three groups: normal cognition, subjective memory complaints, and mild cognitive impairment. At the optimal cut-off score (≥4), the GDS-30 showed 65.1% sensitivity and 68.4% specificity for LLD (63% and 66% for late-life MDD, respectively). Using the standard cut-off score (≥10), the GDS-30 specificity reached 91.2%, while sensitivity dropped to 37.7%, indicating a lower screening accuracy [area under the curve(AUC):0.728, 95% confidence interval(CI):0.67-0-78]. The GDS-30 performance was associated with educational level, but not with age, gender, cognition, apathy, and somatic/psychiatric multimorbidity. For subjective memory complaints subjects, at the optimal cut-off score (≥7), the GDS-30 showed better discrimination performances (AUC=0.792,95%CI:0.60-0.98), but again the educational level affected the diagnostic performance. In subjective memory complaints subjects, symptom-based scales like the GDS-30 may feature a better performance for diagnosing depression in older age, but the GDS-30 seems to require adjustment to the patient's educational level.

Late-onset depression is associated to age-related central auditory processing disorder in an older population in Southern Italy.

The association between late-life depression (LLD) and age-related hearing loss (ARHL) was suggested by preliminary studies, but reliance on LLD subtypes may introduce significant bias. We examined the association between ARHL and LLD according to the age of onset (early-onset depression (EOD) and late-onset depression (LOD)). We investigated the association between ARHL and LLD diagnosed according to the Semi-structured Clinical Diagnostic Interview for DSM-IV-TR in 1749 Italian community-dwelling older subjects from the population-based GreatAGE Study, Southern Italy. Peripheral ARHL was assessed as a pure tone average (PTA) threshold > 40 dB hearing level in the better ear- and age-related CAPD as a score of < 50% to the Synthetic Sentences Identification with Ipsilateral Competitive Message (SSI-ICM) test. LLD amounted at 10.29% of the sample, subdivided in LOD (6.21%) and EOD (4.08%). Age-related CAPD tended to be higher in LOD (28.91%) than in EOD (19.05%). After accounting for covariates, LOD was tendentially associated to age-related CAPD, but not to peripheral ARHL. This trend was confirmed by the linear models in which LOD was significantly associated to worsen SSI-ICM percentages (odds ratio 2.38, 95% confidence interval 1.32-4.30, p = 0.004), but not to PTA values. In a fully adjusted model of LOD, the effect of the association between CAPD and LOD was explained by social dysfunction. LLD was not associated to peripheral ARHL. Age-related CAPD was associated to LOD, a form of depression with cognitive dysfunction hallmark. The ARHL assessment may be an important opportunity to prevent depressive disorders in later life, particularly for LOD.

The relationship between epigenetics and microbiota in neuropsychiatric diseases.

Microbiota might be considered as a pool for environmental epigenetic factors. Evidence is accumulating that environmental exposures - including microbes, diet, drugs - play a role in the pathogenesis of many neuropsychiatric disorders. Underlying mechanisms are complex, involving the sensitive interplay of genetics with epigenetics, neuroinflammation and the innate immune system. Modifications of microbiota affect neurogenesis and the maturation of microglia, influencing social behavior, stress-related responses and fear learning mechanisms. The excitatory neurons in the medial prefrontal cortex appear to play a key role. The mechanisms through which antibiotics administration may modulate microbiota and, therefore, behavior and neuropsychiatric disorders, may be influenced by several variables such as pre-existing gastrointestinal inflammation, the baseline microbiota composition, diet and stress perception. Probiotics, individualized diet, antibiotics and fecal transplantation could positively modulate the effects of epigenetic factors on neuropsychiatric disorders.

Anti-amyloid-ß protein agents for the treatment of Alzheimer's disease: an update on emerging drugs.

INTRODUCTION: Currently available Alzheimer's disease (AD) therapeutics are only symptomatic, targeting cholinergic and glutamatergic neurotransmissions. Several putative disease-modifying drugs in late-stage clinical development target amyloid-ß (Aß) peptide and tau protein, the principal neurophatological hallmarks of the disease. AREAS COVERED: Phase III randomized clinical trials of anti-Aß drugs for AD treatment were searched in US and EU clinical trial registries and principal biomedical databases until May 2020. EXPERT OPINION: At present, compounds in Phase III clinical development for AD include four  anti-Ab monoclonal antibodies (solanezumab, gantenerumab, aducanumab, BAN2401), the combination of cromolyn sodium and ibuprofen (ALZT-OP1), and two small molecules (levetiracetam, GV-971). These drugs are mainly being tested in subjects during early AD phases or at preclinical stage of familial AD or even in asymptomatic subjects at high risk of developing AD. The actual results support the hypothesis that elevated Aß represents an early stage in the AD continuum and demonstrate the feasibility of enrolling these high-risk participants in secondary prevention trials to slow cognitive decline during the AD preclinical stages. However, a series of clinical failures may question further development of Aß-targeting drugs and the findings from current ongoing Phase III trials will hopefully give light to this critical issue.

The Challenge of Antidepressant Therapeutics in Alzheimer's Disease.

The link between depression and Alzheimer's disease (AD) is controversial, because it is not clear if depression is an independent risk factor for the disease or a prodromal symptom in the older population. Cerebral amyloid-ß (Aß) peptide deposition is associated with both cognitive symptoms and neuropsychiatric symptoms (NPS), which may be a biological mechanism of compensation. Despite the widespread use of antidepressant therapeutics (30-50% of patients with AD/dementia are on antidepressants), there is mixed evidence regarding the benefits from their use in AD depression. Monoaminergic antidepressant drugs have shown only modest or no clinical benefits. Therefore, it is important to understand the reason of this drug-resistance and the relationship between antidepressant drugs and the Aß peptide. The goal of the present review is to highlight the etiology of depression in patients affected by AD in comparison to depressive disorders without AD, and to speculate on more appropriate and alternative therapeutics.

The Role of Biomarkers in Psychiatry.

Psychiatric illnesses are cognitive and behavioral disorders of the brain. At present, psychiatric diagnosis is based on DSM-5 criteria. Even if endophenotype specificity for psychiatric disorders is discussed, it is difficult to study and identify psychiatric biomarkers to support diagnosis, prognosis, or clinical response to treatment. This chapter investigates the innovative biomarkers of psychiatric diseases for diagnosis and personalized treatment, in particular post-genomic data and proteomic analyses.

Maladaptive Coping Strategies and Neuroticism Mediate the Relationship Between 5HTT-LPR Polymorphisms and Symptoms of Anxiety in Elite Athletes.

OBJECTIVE: Previous studies have suggested that genetic factors, personality traits and coping strategies might play both independent and interacting roles when influencing stress-related anxiety symptoms. The aim of this study was to examine whether Neuroticism and maladaptive coping strategies mediate the association between the serotonin transporter gene-linked polymorphic region (5HTT-LPR) and symptoms of anxiety and depression in elite athletes who experience high levels of competitive stress. METHOD: One hundred and thirty-three participants were genotyped for the 5-HTTLPR polymorphism and then asked to complete the Cope Orientation to Problems Experienced Inventory and the NEO Five-Factor Inventory. A path analysis was used to test this hypothesis. RESULTS: The 5HTT-LPR was significantly associated with Neuroticism, the coping strategy of Focus on and Venting of Emotions' (FVE) and symptoms of anxiety. FVE and Neuroticism mediated the association between the 5HTT-LPR and symptoms of anxiety (i.e., Cognitive Anxiety and Emotional Arousal Control). Also, Neuroticism was a mediator of the association between the 5HTT-LPR and FVE. Finally, FVE also mediated effects on the relationship between Neuroticism and symptoms of anxiety. CONCLUSIONS: The 5HTT-LPR may affect the susceptibility to develop symptoms of anxiety in elite athletes indirectly through mediation by maladaptive coping strategies and Neuroticism.

Social Dysfunction in Older Age and Relationships with Cognition, Depression, and Apathy: The GreatAGE Study.

BACKGROUND: Most studies focused on only one measure of social dysfunction in older age, without proper validation and distinction across different dimensions including subjectivity, structural, and functional aspects. OBJECTIVE: We sought to validate the Social Dysfunction Rating Scale (SDRS) and its factorial structure, also determining the association of SDRS with cognitive functions, global psychopathology, and social deprivation. METHODS: The SDRS was administered to 484 Italian community-dwelling elderly, recruited in the GreatAGE study, a population-based study on aging conducted in Castellana Grotte, Bari, Southern Italy. We determined objective and subjective psychometric properties of SDRS against the gold standard evaluation of social dysfunction according to the Semi-structured Clinical Diagnostic Interview for DSM-IV-TR Axis I Disorders (SCID-I) criterion. RESULTS: The SDRS showed a moderate accuracy with an optimal cut-off of 26 maximized with higher sensitivity (0.74,95% CI:0.63-0.84) than specificity (0.57,95% CI:0.50-0.64). A five-factor structure was carried out and five dimensions of SDRS were identified (loneliness; social isolation; feeling of contribution/uselessness; lack of leisure activities; anxiety for the health). Education and global cognitive functions were inversely correlated to SDRS, while a direct association with global psychopathology, depression, and apathy was found. The prevalence of higher SDRS scores was major in subjects with current psychiatric disorders versus other subjects.∥Conclusion: The SDRS could be a valid instrument to capture both size and quality of social dysfunction, both in subjects with psychiatric disorders and in normal subjects. Several categories of social dysfunction differed only in the degree of health deprivation, not in social or material deprivation.

Pharmacotherapy for the treatment of depression in patients with alzheimer's disease: a treatment-resistant depressive disorder.

INTRODUCTION: Pharmacotherapy for the treatment of depressive disorders in Alzheimer's Disease (AD) represents a clinical challenge. pharmacological options are often attempted after a period of watchful waiting (8-12 weeks). monoaminergic antidepressant drugs have shown only modest or null clinical benefits, maybe because the etiology of depressive symptoms in ad patients is fundamentally different from that of nondemented subjects. AREAS COVERED: The following article looks at the selective serotonin reuptake inhibitor sertraline, which is one of the most frequently studied antidepressant medications in randomized controlled trials (RCTs). It also discusses many other pharmacological approaches that have proven to be inadequate (antipsychotics, acetylcholinesterase inhibitors, anticonvulsants, hormone replacement therapy) and new drug classes (mainly affecting glutamate transmission) that are being studied for treating depression in AD. It also gives discussion to the phase II RCT on the alternative drug S47445 and the potential effect on cognition of the multimodal antidepressant vortioxetine in older depressed patients. Finally, it discusses the N-methyl-D-aspartate antagonist ketamine. EXPERT OPINION: The present RCT methodologies are too disparate to draw firm conclusions. Future studies are required to identify effective and multimodal pharmacological treatments that efficiently treat depression in AD. Genotyping may boost antidepressant treatment success.

Different Cognitive Frailty Models and Health- and Cognitive-related Outcomes in Older Age: From Epidemiology to Prevention.

Frailty, a critical intermediate status of the aging process that is at increased risk for negative health-related events, includes physical, cognitive, and psychosocial domains or phenotypes. Cognitive frailty is a condition recently defined by operationalized criteria describing coexisting physical frailty and mild cognitive impairment (MCI), with two proposed subtypes: potentially reversible cognitive frailty (physical frailty/MCI) and reversible cognitive frailty (physical frailty/pre-MCI subjective cognitive decline). In the present article, we reviewed the framework for the definition, different models, and the current epidemiology of cognitive frailty, also describing neurobiological mechanisms, and exploring the possible prevention of the cognitive frailty progression. Several studies suggested a relevant heterogeneity with prevalence estimates ranging 1.0-22.0% (10.7-22.0% in clinical-based settings and 1.0-4.4% in population-based settings). Cross-sectional and longitudinal population-based studies showed that different cognitive frailty models may be associated with increased risk of functional disability, worsened quality of life, hospitalization, mortality, incidence of dementia, vascular dementia, and neurocognitive disorders. The operationalization of clinical constructs based on cognitive impairment related to physical causes (physical frailty, motor function decline, or other physical factors) appears to be interesting for dementia secondary prevention given the increased risk for progression to dementia of these clinical entities. Multidomain interventions have the potential to be effective in preventing cognitive frailty. In the near future, we need to establish more reliable clinical and research criteria, using different operational definitions for frailty and cognitive impairment, and useful clinical, biological, and imaging markers to implement intervention programs targeted to improve frailty, so preventing also late-life cognitive disorders.

An Old Challenge with New Promises: A Systematic Review on Comprehensive Geriatric Assessment in Long-Term Care Facilities.

Comprehensive geriatric assessment (CGA) is a multidimensional and multidisciplinary diagnostic process focused on determining the clinical profile, pathological risk, residual skills, short- and long-term prognosis, and personalized therapeutic and care plan of the functionally compromised and frail older subjects. Previous evidence suggested that the effectiveness of CGA programs may be influenced by settings where the CGA is performed [i.e., hospital, posthospital discharge/long-term care facilities (LTCFs), or community/home] as well as the specific clinical conditions of older frail individuals. In this scenario, CGA and quality of care in LTCFs have been a challenge for decades. In the present article, we systematically reviewed evidence from the last three decades of clinical research devoted to systematic implementation of CGA programs in LTCFs, that is, nursing homes, care homes, residential homes, and rehabilitation facilities. In the United States, all LTC residents must undergo a CGA on a regular basis on admission to a facility, prompting the development of the Resident Assessment Instrument (RAI) Minimum Data Set, a specific CGA-based assessment tool in this population. In the LTCF setting, the present reviewed evidence suggested that most complex older subjects may benefit from a CGA in terms of improved quality of care and reduced hospitalization events and that CGA must be standardized across healthcare settings to promote greater health system integration and coordination. In the LTCF setting, particularly in nursing homes, other new and promising CGA programs have also been proposed to develop rapid screening CGA-based tools to enhance in the future the ability of primary care physicians to recognize and treat geriatric syndromes in this setting. However, at present, the interRAI suite of instruments represented an integrated health information system that has the potential to provide person-centered information transcending healthcare settings.