Platelets and Neurodegenerative Diseases: Current Knowledge and Future Perspectives.

Platelets have a fundamental role in mediating hemostasis and thrombosis. However, more recently, a new idea is making headway, highlighting the importance of platelets as significant actors in modulating immune and inflammatory responses. In particular, platelets have an important role in the development of vascular amyloid-b-peptide(ab) deposits, known to play a relevant role in Alzheimer's disease (AD) through accumulation and deposition within the frontal cortex and hippocampus in the brain. The involvement of platelets in the pathogenesis of AD opens up the highly attractive possibility of applying antiplatelet therapy for the treatment and/or prevention of AD, but conclusive results are scarce. Even less is known about the potential role of platelets in mild cognitive impairment (MCI). The aim to this brief review is to summarize current knowledge on this topic and to introduce the new perspectives on the possible role of platelet activation as therapeutic target both in AD and MCI.

Prevalence of dyslipidemia and hypercholesterolemia awareness: results from the Lookup 7+ online project.

BACKGROUND: Cardiovascular disease still represents the leading cause of death worldwide. Management of risk factors remains crucial; despite this, hypercholesterolemia, which is one of the most important modifiable cardiovascular risk factor, is still high prevalent in general population. The aim of this study is to determine the prevalence of dyslipidemia and hypercholesterolemia awareness in a very large population. METHODS: More than 65 000 users completed the online, self-administered survey. It was structured like a 'journey' where each stage corresponded to a cardiovascular risk factor: blood pressure, body mass index, cholesterol, diet, physical exercise, smoke and blood sugar. At the end, the user received a final evaluation of his health status. RESULTS: The mean age was 52.5 years (SD 13.9, range 18-98), with 35 402 (53.7%) men. About 56% of all participants believed to have normal cholesterol values, when only 40% of them really showed values <200 mg/dl. Only about 30% of all participants self-predicted to have abnormal cholesterol values whereas we found high cholesterol levels in about 60% of people. CONCLUSIONS: Dyslipidemia is very prevalent and half of the people with high cholesterol is not aware of having high values.

What about the caregiver? A journey into Parkinson's disease following the burden tracks.

OBJECTIVES: To investigate caregivers and patients characteristics related to different dimensions of burden in Parkinson's disease (PD). METHODS: 55 pairs of PD patients and caregivers were recruited. The burden was evaluated with the Caregiver Burden Inventory (CBI). Multivariate analysis was applied to evaluate the impact of caregivers' and patients' characteristics on the varying aspects of burden. RESULTS: ADL score was the dominant predictor for the total score and all dimensions of CBI, except for the social burden, which is strongly predicted by the motor severity of PD. As one can easily imagine, the Total CBI decreases as the ADL score increases. DISCUSSION: An increased appreciation for characteristics of caregiver burden is a fundamental aspect of the patient's global evaluation. Clinicians may need to directly probe for these factors in the caregiver as they may not be elicited routinely.

Prevalence of Obsessive-Compulsive Symptoms in Elderly Parkinson Disease Patients: A Case-Control Study.

BACKGROUND: The clinical picture of obsessive-compulsive disorder encompasses a broad range of symptoms that are related to multiple psychological domains, including perception, cognition, emotion, and social relatedness. As obsessive-compulsive symptoms (OCS) frequently have an early onset, there are limited data about OCS in older populations (≥65 years) and, in particular, in elderly subjects with Parkinson disease (PD). OBJECTIVE: This study aimed to estimate the prevalence of OCS using a self-report measure (Obsessive-Compulsive Inventory-Revised) and to identify associated sociodemographic and clinical factors in a sample of elderly PD patients compared to a comparison group of similarly aged healthy volunteers. RESULTS: The mean age was 74 ± 6 years in the PD patients and 73 ± 7 years in the comparison group. The mean disease duration was 9.6 ± 5.8 years. Among the PD patients, 30.7% reported at least one OCS or a related disorder compared to 21.1% in the comparison group. Hoarding was significantly more common in PD patients than in the comparison group. CONCLUSIONS: Subclinical OCS were present at a high percentage in both PD patients and comparison group. The OCS phenotype in PD may present differently, as hoarding was more common in PD patients.

Use of antidepressant medications among older adults in European long-term care facilities: a cross-sectional analysis from the SHELTER study.

BACKGROUND: Late-life depression is common among older adults living in nursing homes (NHs). Over the last 30 years there has been an increase in the rates of prescription of antidepressant medications across all ages, with the largest rise reported in older adults. This study aimed to describe the pattern of antidepressant medication use among NH residents from 7 European countries and Israel and to examine patient and facilities characteristics that may account for it. METHODS: We conducted a cross-sectional analysis of data from the SHELTER study, an observational longitudinal cohort study that collected comprehensive resident data using the interRAI Long-Term Care Facility instrument in 7 European Countries and Israel. Descriptive statistics were used to examine sample characteristics. Potential correlates of antidepressant medication use were identified using multiple logistic regression modeling. RESULTS: Among 4023 residents entering the study, 32% had depressive symptoms and nearly half of these individuals used antidepressants. Antidepressant medication use varied by country, with a prevalence in the overall sample of 35.6% (n = 1431). Among antidepressant users, 59.9% were receiving selective serotonin reuptake inhibitors (SSRI). The strongest correlates of antidepressant use included reported diagnosis of anxiety, depression, bipolar disorder, pain, falls and high level of social engagement. Age over 85 years, living in facilities located in rural areas and a diagnosis of schizophrenia reduced the likelihood of being prescribed with an antidepressant. CONCLUSIONS: A large proportion of residents in European long-term care facilities receive antidepressant medications. The decision to prescribe antidepressants to NH residents seems to be influenced by both patient and facility characteristics. Future longitudinal studies should evaluate the efficacy and safety of antidepressant use in NHs thus providing evidence for recommendations for clinical practice.

Mild cognitive impairment and microbiota: what is known and future perspectives.

Mild cognitive impairment (MCI) is a heterogeneous condition definable as the intermediate clinical state between normal aging and dementia. As a pre-dementia condition, there is a recent growing interest in the identification of non-invasive markers able to predict the progression from MCI to a more advanced stage of the disease. Previous evidence showed the close link between gut microbiota and neurodegenerative diseases, such as Alzheimer's (AD) and Parkinson's disease (PD). Conversely, the actual relationship between gut microbiota and MCI is yet to be clarified. In this work, we provide an overview about the current knowledge regarding the role of gut microbiota in the context of MCI, also assessing the potential for microbiota-targeted therapies. Through the review of the most recent studies focusing on this topic, we found evidence of an increase of Bacteroidetes at phylum level and Bacteroides at genus level in MCI subjects with respect to healthy controls and patients with AD. Despite such initial evidence, the definitive identification of a typical microbiota profile associated with MCI is still far from being achieved. These preliminary results, however, are growingly encouraging research on the role of gut microbiota modulation in improving the cognitive status of pre-dementia subjects. To date, few studies evaluated the role of probiotics in MCI subjects, and they showed favorable results, although still biased by small sample size, heterogeneity of study design and short follow-up.

Association of Delirium and Depression with Respiratory and Outcome Measures in COVID-19 Inpatients.

Delirium (DEL) and depression (DEP) may impair the course and severity of acute respiratory illness. The impact of such syndromes on respiratory and outcome parameters in inpatients with COVID-19 needs clarification. To clarify the relationship between DEL and DEP and respiratory outcome measures, we enrolled 100 inpatients from COVID-19 units of the Fondazione Policlinico Universitario Agostino Gemelli IRCCS of Rome. Participants were divided into those with DEL, DEP, or absence of either delirium or depression (CONT). Delirium severity was assessed with the Neelson and Champagne Confusion Scale (NEECHAM). Psychopathology was assessed with the Hamilton Rating Scale for Depression (HAM-D), the Hamilton Rating Scale for Anxiety (HAM-A), and the Brief Psychiatric Rating Scale (BPRS). Dependent variables include: (a) respiratory parameters, i.e., partial pressure of oxygen in arterial blood (PaO2), oxygen saturation (SpO2), ratio between arterial partial pressure of oxygen (PaO2), and fraction of inspired oxygen (PaO2/FiO2); (b) outcome parameters, i.e., duration of hospitalization and number of pharmacological treatments used during the hospitalization. We investigated between-group differences and the relationships between severity of delirium/depression and the dependent variables. Duration of hospitalization was longer for DEL than for either DEP or CONT and for DEP compared to CONT. NEECHAM and HAM-D scores predicted lower PaO2 and PaO2/FiO2 levels in the DEL and DEP groups, respectively. In DEP, BPRS scores positively correlated with duration of hospitalization. Delirium impacted the course of COVID-19 more severely than depression. The mechanisms by which delirium and depression worsen respiratory parameters differ.

Association between Older Age and Psychiatric Symptoms in a Population of Hospitalized Patients with COVID-19.

Increased rates of anxiety and depression have been reported for older adults during the COVID-19 pandemic. However, little is known regarding the onset of mental health morbidity during the acute phase of the disease and the role of age as potential independent risk factor for psychiatric symptoms. The cross-sectional association between older age and psychiatric symptoms has been estimated in a sample of 130 patients hospitalized for COVID-19 during the first and second wave of the pandemic. Compared to younger patients, those who were 70 years of age or older resulted at a higher risk of psychiatric symptoms measured on the Brief Psychiatric Symptoms Rating Scale (BPRS) (adjusted (adj.) odds ratio (OR) 2.36, 95% confidence interval (CI) 1.05-5.30) and delirium (adj. OR 5.24, 95% CI 1.63-16.8)). No association was found between older age and depressive symptoms or anxiety. Age was associated with psychiatric symptoms independently of gender, marital status, history of psychiatric illness, severity of disease and cardiovascular morbidity. Older adults appear at high risk of developing psychiatric symptoms related to COVID-19 disease during hospital stay. Multidisciplinary preventive and therapeutic interventions should be implemented to reduce the risk of psychiatric morbidity and related adverse health care outcomes among older hospital inpatients with COVID-19.

Frailty modifies the effect of polypharmacy and multimorbidity on the risk of death among nursing home residents: Results from the SHELTER study.

Background: Frailty, disability, and polypharmacy are prevalent in nursing home (NH) residents, often co-occurring with multimorbidity. There may be a complex interplay among them in terms of outcomes such as mortality. Aims of the study were to (i) assess whether nursing home residents with polypharmacy (5-9 medications) or hyperpolypharmacy (≥10 drugs), have an increased risk of death and (ii) whether any association is modified by the co-presence of frailty or disability. Methods: Cohort study with longitudinal mortality data including 4,023 residents from 50 European and 7 Israeli NH facilities (mean age = 83.6 years, 73.2% female) in The Services and Health for Elderly in Long Term care (SHELTER) cohort study. Participants were evaluated with the interRAI-LongTerm Care assessment tool. Frailty was evaluated with the FRAIL-NH scale. Hazard ratio (HR) of death over 12 months was assessed with stratified Cox proportional hazards models adjusted for demographics, facilities, and cognitive status. Results: 1,042 (25.9%) participants were not on polypharmacy, 49.8% (n = 2,002) were on polypharmacy, and 24.3% (n = 979) on hyperpolypharmacy. Frailty and disability mostly increased risk of death in the study population (frailty: HR = 1.85, 95%CI 1.49-2.28; disability: HR = 2.10, 95%CI 1.86-2.47). Among non-frail participants, multimorbidity (HR = 1.34, 95%CI = 1.01-1.82) and hyperpolypharmacy (HR = 1.61, 95%CI = 1.09-2.40) were associated with higher risk of death. Among frail participants, no other factors were associated with mortality. Polypharmacy and multimorbidity were not associated with mortality after stratification for disability. Conclusions: Frailty and disability are the strongest predictors of death in NH residents. Multimorbidity and hyperpolypharmacy increase mortality only in people without frailty. These findings may be relevant to identify patients who could benefit from tailored deprescription.

Neuropsychiatric Symptoms in Elderly With Dementia During COVID-19 Pandemic: Definition, Treatment, and Future Directions.

BACKGROUND: Neuropsychiatric symptoms (NPS) of dementia, such as anxiety, depression, agitation, and apathy, are complex, stressful, and costly aspects of care, and are associated to poor health outcomes and caregiver burden. A steep worsening of such symptoms has been reported during Coronavirus Disease 2019 (COVID-19) pandemic. However, their causes, their impact on everyday life, and treatment strategies have not been systematically assessed. Therefore, the aim of this review is to provide a detailed description of behavioral and psychopathological alterations in subjects with dementia during COVID-19 pandemic and the associated management challenges. METHODS: A PubMed search was performed focusing on studies reporting alterations in behavior and mood and treatment strategies for elderly patients with dementia, in accordance with PRISMA guidelines. The following search strategy was utilized: (COVID* OR coronavirus OR "corona vir*" OR SARS-CoV-2) AND (dementia OR demented OR dement* OR alzheimer* OR "pick's disease" OR "lewy body" OR "mild cognitive" OR mild cognitive impairment OR MCI). RESULTS: Apathy, anxiety and agitation are the most frequently NPS during the COVID-19 pandemic and are mainly triggered by protracted isolation. Most treatment strategies rely on pharmacotherapy; technology is increasingly utilized with mixed results. CONCLUSIONS: NPS of dementia during COVID-19 appear to arise from social restrictions occurring as a consequence of the pandemic. Implementation of caregiver support and the presence of skilled nursing home staff are required to restore social interaction and adjust technological support to the patients' needs.

The "develOpment of metabolic and functional markers of Dementia IN Older people" (ODINO) Study: Rationale, Design and Methods.

Mild cognitive impairment (MCI), also termed mild neurocognitive disorder, includes a heterogeneous group of conditions characterized by declines in one or more cognitive domains greater than that expected during "normal" aging but not severe enough to impair functional abilities. MCI has been associated with an increased risk of developing dementia and even considered an early stage of it. Therefore, noninvasively accessible biomarkers of MCI are highly sought after for early identification of the condition. Systemic inflammation, metabolic perturbations, and declining physical performance have been described in people with MCI. However, whether biological and functional parameters differ across MCI neuropsychological subtypes is presently debated. Likewise, the predictive value of existing biomarkers toward MCI conversion into dementia is unclear. The "develOpment of metabolic and functional markers of Dementia IN Older people" (ODINO) study was conceived as a multi-dimensional investigation in which multi-marker discovery will be coupled with innovative statistical approaches to characterize patterns of systemic inflammation, metabolic perturbations, and physical performance in older adults with MCI. The ultimate aim of ODINO is to identify potential biomarkers specific for MCI subtypes and predictive of MCI conversion into Alzheimer's disease or other forms of dementia over a three-year follow-up. Here, we describe the rationale, design, and methods of ODINO.

The Geriatrician: The Frontline Specialist in the Treatment of COVID-19 Patients.

On February 20, 2020, a man living in the north of Italy was admitted to the emergency room with an atypical pneumonia that later proved to be COVID-19. This was the trigger of one of the most serious clusters of COVID-19 in the world, outside of China. Despite aggressive restraint and inhibition efforts, COVID-19 continues to increase, and the total number of infected patients in Italy is growing daily. After 6 weeks, the total number of patients reached 128,948 cases (April 5, 2020), with the higher case-fatality rate (15,887 deaths) dominated by old and very old patients. This sudden health emergency severely challenged the Italian Health System, in particular acute care hospitals and intensive care units. In 1 hospital, geriatric observation units were created, the experience of which can be extremely useful for European countries, the United States, and all countries that in the coming days will face a similar situation.

Deprescribing in Nursing Home Residents on Polypharmacy: Incidence and Associated Factors.

OBJECTIVES: To assess 1-year incidence and factors related to deprescribing in nursing home (NH) residents in Europe. DESIGN: Longitudinal multicenter cohort study based on data from the Services and Health for Elderly in Long TERm care (SHELTER) study. SETTING: NHs in Europe and Israel. PARTICIPANTS: 1843 NH residents on polypharmacy. METHODS: Polypharmacy was defined as the concurrent use of 5 or more medications. Deprescribing was defined as a reduction in the number of medications used over the study period. Residents were followed for 12 months. RESULTS: Residents in the study sample were using a mean number of 8.6 (standard deviation 2.9) medications at the baseline assessment. Deprescribing was observed in 658 residents (35.7%). Cognitive impairment (mild/moderate impairment vs intact, odds ratio [OR] 1.41, 95% confidence interval [CI] 1.11-1.79; severe impairment vs intact, OR 1.60, 95% CI 1.23-2.09), presence of the geriatrician within the facility staff (OR 1.41, 95% CI 1.15-1.72), and number of medications used at baseline (OR 1.10, 95% CI 1.06-1.14) were associated with higher probabilities of deprescribing. In contrast, female gender (OR 0.76, 95% CI 0.61-0.96), heart failure (OR 0.69, 95% CI 0.53-0.89), and cancer (OR 0.64, 95% CI 0.45-0.90) were associated with a lower probability of deprescribing. CONCLUSIONS AND IMPLICATIONS: Deprescribing is common in NH residents on polypharmacy, and it is associated with individual and organizational factors. More evidence is needed on deprescribing, and clear strategies on how to withdraw medications should be defined in the future.

Association of Polypharmacy With 1-Year Trajectories of Cognitive and Physical Function in Nursing Home Residents: Results From a Multicenter European Study.

OBJECTIVES: To test the association between polypharmacy and 1-year change in physical and cognitive function among nursing home (NH) residents. DESIGN: Longitudinal multicenter cohort study based on data from the Services and Health for Elderly in Long TERm care (SHELTER) study. SETTING: NH in Europe (n = 50) and Israel (n = 7). PARTICIPANTS: 3234 NH older residents. MEASUREMENTS: Participants were assessed through the interRAI long-term care facility instrument. Polypharmacy was defined as the concurrent use of 5 to 9 drugs and excessive polypharmacy as the use of ≥10 drugs. Cognitive function was assessed through the Cognitive Performance Scale (CPS). Functional status was evaluated through the Activities of Daily Living (ADL) Hierarchy scale. The change in CPS and ADL score, based on repeated assessments, was the outcome, and their association with polypharmacy was modeled via linear mixed models. The interaction between polypharmacy and time was reported [beta and 95% confidence intervals (95% CIs)]. RESULTS: A total of 1630 (50%) residents presented with polypharmacy and 781 (24%) excessive polypharmacy. After adjusting for potential confounders, residents on polypharmacy (beta 0.10, 95% CI 0.01-0.20) and those on excessive polypharmacy (beta 0.13, 95% CI 0.01-0.24) had a significantly higher decline in CPS score compared to those using <5 drugs. No statistically (P > .05) significant change according to polypharmacy status was shown for ADL score. CONCLUSIONS: Polypharmacy is highly prevalent among older NH residents and, over 1 year, it is associated with worsening cognitive function but not functional decline.

Chewing problems and mortality in older adults in home care: results from the Aged in Home Care study.

OBJECTIVES: To assess the association between chewing problems and risk of mortality in an older population receiving home care in Europe. DESIGN: Retrospective cohort study. SETTING: Eleven European countries. PARTICIPANTS: Two thousand seven hundred fifty-five older adults (mean age+/-standard deviation 82.2+/-7.2) in home care. MEASUREMENTS: Data were collected using the Minimum Data Set for Home Care. Study personnel recorded chewing problems (inability to chew food easily and without pain or difficulties, regardless of cause) that presented in the last 3 days before baseline assessment. Data on mortality were collected over a 1-year period. RESULTS: Three hundred ninety-five participants (14.3%) presented with chewing problems. One-year mortality differed significantly according to presence of chewing problems; 303 of 2,361 (12.8%) without chewing problems (crude incident rate per person-year (p-y)=0.15) and 80 of 394 (20.3%) participants with chewing problems (crude incident rate per p-y=0.24) died during follow-up. After adjusting for potential confounders, the risk of death was significantly higher for participants with chewing problems (adjusted hazard ratio (HR)=1.45, 95% confidence intervals (CI)=1.05-1.99). This association remained after exclusion of participants with cognitive impairment (adjusted HR=1.50, 95% CI=1.03-2.20) and those with unintended weight loss (adjusted HR=1.62, 95% CI=1.12-2.34). CONCLUSION: In older adults in home care in Europe, chewing problems are associated with greater risk of mortality.

Depression and risk of nursing home admission among older adults in home care in Europe: results from the Aged in Home Care (AdHOC) study.

OBJECTIVE: Depression is a frequent condition observed among nursing home residents. However, so far, limited data are available on the impact of depression on nursing home admission. The aim of the present study was to assess the effect of depression on the risk of nursing home admission in a group of older adults receiving home care in Europe. METHOD: We conducted a longitudinal analysis using data from the Aged in Home Care (AdHOC) database, which contains information on older adults receiving home care services in 11 European countries. Subjects had been admitted to the home care programs between 2001 and 2003. Depression was diagnosed as a score >or=3 on the Minimum Data Set (MDS) Depression Rating Scale. Information on nursing home admission was collected semiannually for 1 year by trained research personnel. RESULTS: The mean age of 2718 older adults entering the study was 82.4 (SD = 7.3) years, 2047 (75.3%) were women, and 331 (12.2%) were depressed. Overall, 49/331 depressed participants (14.8%) and 252/2387 nondepressed participants (10.6%) were admitted to a nursing home (p = .02). After adjusting for potential confounders, the risk of nursing home admission was significantly higher for depressed participants (hazard ratio = 1.43, 95% CI = 1.02 to 2.02). The risk of nursing home admission progressively and significantly increased as MDS Depression Rating Scale score increased (signifying more severe depression) (p = .001 for linear trend). CONCLUSIONS: In older adults receiving home care in Europe, depression is associated with an increased risk for nursing home admission. This association increases with severity of depression.