Frailty trajectories in community-dwelling older adults during COVID-19 pandemic: The PRESTIGE study.

BACKGROUND: Frailty has been recognized as potential surrogate of biological age and relevant risk factor for COVID-19 severity. Thus, it is important to explore the frailty trajectories during COVID-19 pandemic and understand how COVID-19 directly and indirectly impacts on frailty condition. METHODS: We enrolled 217 community-dwelling older adults with available information on frailty condition as assessed by multidimensional frailty model both at baseline and at one-year follow-up using Multidimensional Prognostic Index (MPI) tools. Pre-frail/frail subjects were identified at baseline as those with MPI score >0.33 (MPI grades 2-3). Frailty worsening was defined by MPI difference between 12 months follow-up and baseline ≥0.1. Multivariable logistic regression was modelled to identify predictors of worsening of frailty condition. RESULTS: Frailer subjects at baseline (MPI grades 2-3 = 48.4%) were older, more frequently female and had higher rates of hospitalization and Sars-CoV-2 infection compared to robust ones (MPI grade 1). Having MPI grades 2-3 at baseline was associated with higher risk of further worsening of frailty condition (adjusted odd ratio (aOR): 13.60, 95% confidence interval (CI): 4.01-46.09), independently by age, gender and Sars-CoV-2 infection. Specifically, frail subjects without COVID-19 (aOR: 14.84, 95% CI: 4.26-51.74) as well as those with COVID-19 (aOR: 12.77, 95% CI: 2.66-61.40, p = 0.001) had significantly higher risk of worsening of frailty condition. CONCLUSIONS: Effects of COVID-19 pandemic among community-dwelling frailer individuals are far beyond the mere infection and disease, determining a significant deterioration of frailty status both in infected and non-infected subjects.

Multidimensional Frailty Predicts Mortality Better than Physical Frailty in Community-Dwelling Older People: A Five-Year Longitudinal Cohort Study.

Frailty is a common syndrome in older people that carries an increased risk of mortality. Two main models describe frailty, either as a loss of physical functions or as an accumulation of multiple deficits. The aim of our study was to compare the physical frailty index developed in the Cardiovascular Health Study (CHS) with a multidimensional frailty tool, the Multidimensional Prognostic Index (MPI), in predicting death in community-dwelling older subjects. Four hundred and seven community-dwelling older subjects were enrolled. Each subject underwent a comprehensive geriatric assessment (CGA) with calculation of the MPI and CHS index. Mortality was recorded over the following 5 years. In the overall sample (mean age of 77.9 ± 4.5 years; 51.6% female), 53 subjects (13%) died during the 5-year follow-up period. Both the MPI and CHS index were able to predict mortality; however, the MPI was significantly more accurate than the CHS index in predicting mortality (C-index = 0.69 and 0.59, respectively; p < 0.001), with a statistically significant difference of 10%. In conclusion, multidimensional frailty, assessed by the MPI, predicts five-year mortality in community-dwelling older people better than physical frailty, as assessed by the CHS index. These findings suggest the usefulness of assessing frailty by means of CGA-based tools to predict relevant health-negative outcomes in older people.

Validation and implementation of telephone-administered version of the Multidimensional Prognostic Index (TELE-MPI) for remote monitoring of community-dwelling older adults.

BACKGROUND: During the recent lockdown measures adopted by national authorities to contain the COVID-19 pandemic, many vulnerable older patients with chronic conditions, normally followed in ambulatory setting, needed to be monitored and managed in alternative ways, including telemedicine. AIMS: In the framework of a telemedicine program, we aimed to validate and implement a telephone-administered version of the Multidimensional Prognostic Index (TELE-MPI) among community-dwelling older outpatients. METHOD: From March 9 to May 11, 2020, 131 older patients (82.1 years; 74% females) were interviewed using a telephone-based survey to calculate the TELE-MPI. The standard MPI was performed face-to-face three months apart. The Bland-Altman methodology measured the agreement between the two tools. Multivariate logistic regression models were built to ascertain the prognostic value of TELE-MPI and TELE-MPI classes (low, moderate, or severe risk) on negative outcomes occurring during the lockdown period. RESULTS: Mean MPI and TELE-MPI values were 0.523 and 0.522, respectively. Lower and upper 95% limits of agreement were - 0.122 and + 0.124, respectively, with only 4.6% of observations outside the limits. Each 0.1 increase of TELE-MPI score was significantly correlated with higher incidence of psychiatric disorders [odd ratio (OR): 1.57; 95% confidence interval (CI) 1.27, 1.95] and falls (OR: 1.41; 95% CI 1.08, 1.82) in community-dwelling-older adults. DISCUSSION: TELE-MPI showed a strong agreement with the standard MPI and was able to predict psychiatric disorders and falls during lockdown period. CONCLUSION: TELE-MPI may represent a useful way to follow by remote the health status of older adults.

Multidimensional prognostic index (MPI) predicts successful application for disability social benefits in older people.

AIM: The economic recognition of disability is of importance in daily practice, but the tools used in older people are still limited. Therefore, we aimed to investigate the effectiveness of the multidimensional prognostic index (MPI) to identify frail older subjects to be submitted to civil invalidity application for disability benefits including Attendance Allowance (AA) indemnity, Carer's Leave (Law 104) and/or Parking Card for people with disabilities. METHODS: From March 2018 to January 2019, 80 older people were included. The MPI was calculated from comprehensive geriatric assessment information including eight different domains. Civil benefits included attendance allowance (AA) indemnity by the Local Medico-Legal Committee (MLC-NHS) and by the National Institute of Social Security Committee (INPS), Carer's Leave (Law 104), and Parking Card for people with disabilities. RESULTS: MPI values were associated with an increased probability to obtain a 100% civil disability, AA indemnity, Carer's Leave and a parking card for people with disabilities. MPI score showed a very good accuracy in predicting the civil invalidity benefits with a area-under-curve (AUC) of 87.3 (95% CI 80.6-97.4) to predict the release of AA indemnity, 81.3 (95% CI 68.5-91.1) to predict Care's leave and 70.7 (95% CI 59.4-84.7) to predict the Parking Card release. Moreover, data showed that a cut-off score of MPI ≥ 0.75 could identify the 100% of older subjects who successfully obtained the indemnity release. CONCLUSION: MPI is an excellent predictor of social benefits' release by local and national agencies.

Association of Antidementia Drugs and Mortality in Community-Dwelling Frail Older Patients With Dementia: The Role of Mortality Risk Assessment.

OBJECTIVE: To evaluate whether treatment with antidementia drugs is associated with reduced mortality in older patients with different mortality risk at baseline. DESIGN: Retrospective. SETTING: Community-dwelling. PARTICIPANTS: A total of 6818 older people who underwent a Standardized Multidimensional Assessment Schedule for Adults and Aged Persons (SVaMA) evaluation to determine accessibility to homecare services or nursing home admission from 2005 to 2013 in the Padova Health District, Italy were included. MEASUREMENTS: Mortality risk at baseline was calculated by the Multidimensional Prognostic Index (MPI), based on information collected with the SVaMA. Participants were categorized to have mild (MPI-SVaMA-1), moderate (MPI-SVaMA-2), and high (MPI-SVaMA-3) mortality risk. Propensity score-adjusted hazard ratios (HR) of 2-year mortality were calculated according to antidementia drug treatment. RESULTS: Patients treated with antidementia drugs had a significant lower risk of death than untreated patients (HR 0.82; 95% confidence interval [CI] 0.73-0.92 and 0.56; 95% CI 0.49-0.65 for patients treated less than 2 years and more than 2 years treatment, respectively). After dividing patients according to their MPI-SVaMA grade, antidementia treatment was significantly associated with reduced mortality in the MPI-SVaMA-1 mild (HR 0.71; 95% CI 0.54-0.92) and MPI-SVaMA-2 moderate risk (HR 0.61; 95% CI 0.40-0.91, matched sample), but not in the MPI-SVaMA-3 high risk of death. CONCLUSIONS: This large community-dwelling patient study suggests that antidementia drugs might contribute to increased survival in older adults with dementia with lower mortality risk.

Three Decades of Comprehensive Geriatric Assessment: Evidence Coming From Different Healthcare Settings and Specific Clinical Conditions.

Comprehensive geriatric assessment (CGA) is a multidisciplinary diagnostic and treatment process that identifies medical, psychosocial, and functional capabilities of older adults to develop a coordinated plan to maximize overall health with aging. Specific criteria used by CGA programs to evaluate patients include age, medical comorbidities, psychosocial problems, previous or predicted high healthcare utilization, change in living situation, and specific geriatric conditions. However, no universal criteria have been agreed upon to readily identify patients who are likely to benefit from CGA. Evidence from randomized controlled trials and large systematic reviews and meta-analyses suggested that the healthcare setting may modify the effectiveness of CGA programs. Home CGA programs and CGA performed in the hospital were shown to be consistently beneficial for several health outcomes. In contrast, the data are conflicting for posthospital discharge CGA programs, outpatient CGA consultation, and CGA-based inpatient geriatric consultation services. The effectiveness of CGA programs may be modified also by particular settings or specific clinical conditions, with tailored CGA programs in older frail patients evaluated for preoperative assessment, admitted or discharged from emergency departments and orthogeriatric units or with cancer and cognitive impairment. CGA is capable of effectively exploring multiple domains in older age, being the multidimensional and multidisciplinary tool of choice to determine the clinical profile, the pathologic risk and the residual skills as well as the short- and long-term prognosis to facilitate the clinical decision making on the personalized care plan of older persons.

Tau-based therapeutics for Alzheimer's disease: active and passive immunotherapy.

Pharmacological manipulation of tau protein in Alzheimer's disease included microtubule-stabilizing agents, tau protein kinase inhibitors, tau aggregation inhibitors, active and passive immunotherapies and, more recently, inhibitors of tau acetylation. Animal studies have shown that both active and passive approaches can remove tau pathology and, in some cases, improve cognitive function. Two active vaccines targeting either nonphosphorylated (AAD-vac1) and phosphorylated tau (ACI-35) have entered Phase I testing. Notwithstanding, the recent discontinuation of the monoclonal antibody RG7345 for Alzheimer's disease, two other antitau antibodies, BMS-986168 and C2N-8E12, are also currently in Phase I testing for progressive supranuclear palsy. After the recent impressive results in animal studies obtained by salsalate, the dimer of salicylic acid, inhibitors of tau acetylation are being actively pursued.

Progresses in treating agitation: a major clinical challenge in Alzheimer's disease.

INTRODUCTION: Treatment of neuropsychiatric symptoms (NPS) represents a major clinical challenge in Alzheimer's disease (AD). Agitation and aggression are frequently seen during institutionalization and increase patient morbidity and mortality and caregiver burden. Off-label use of atypical antipsychotics for treating agitation in AD showed only modest clinical benefits, with high side-effect burden and risk of mortality. Non-pharmacological treatment approaches have become the preferred first-line option. When such treatment fails, pharmacological options are often used. Therefore, there is an urgent need to identify effective and safe pharmacological treatments for efficiently treating agitation and aggression in AD and dementia. AREAS COVERED: Emerging evidence on the neurobiological substrates of agitation in AD has led to several recent clinical trials of repositioned and novel therapeutics for these NPS in dementia as an alternative to antipsychotics. We operated a comprehensive literature search for published articles evaluating pharmacological interventions for agitation in AD, with a review of recent clinical trials on mibampator, dextromethorphan/quinidine, cannabinoids, and citalopram. EXPERT OPINION: Notwithstanding the renewed interest for the pharmacological treatment of agitation in AD, progresses have been limited. A small number and, sometimes methodologically questionable, randomized controlled trials (RCTs) have produced disappointing results. However, recently completed RCTs on novel or repositioned drugs (mibampator, dextromethorphan/quinidine, cannabinoids, and citalopram) showed some promise in treating agitation in AD, but still with safety concerns. Further evidence will come from ongoing Phase II and III trials on promising novel drugs for treating these distressing symptoms in patients with AD and dementia.

Clinically non-functioning pituitary macroadenomas in the elderly.

BACKGROUND AND AIMS: The aim of the present study was to evaluate the clinical presentation, characteristics and post-surgical outcome of non-functioning pituitary macroadenomas (NFPM) in elderly patients. METHODS: 27 patients (65-81 years; 13 Males, 14 Females) with NFPM (20-45 mm in diameter) were studied. The symptoms prompting neuroradiological studies were vision alterations in 52%, and dizziness, loss of memory, confusion, headache and depression in 29%; in 19% of patients, the disease was incidentally discovered during computed tomography (CT) or magnetic resonance imaging (MRI) for head trauma or cerebral ischemic attacks. RESULTS: Endocrinological evaluation on diagnosis showed global anterior hypopituitarism in 33% and partial hypopituitarism in 37% of patients. Immunohistochemistry showed signs of neurosecretion in most NFPM (chromogranin-A in 55%, gonadotropins in 19%, ACTH in 3.7%). Ki-67 antigen expression was indicative of low proliferative activity. Surgery was highly effective in improving alterations in vision and compressive symptoms, but was unable to restore normal pituitary function in established hypopituitarism in most cases. Eight patients (31%) were free of disease on subsequent MRI (follow-up 1-6 years). In 18 (69%) patients, a post-surgical residue was present. Of these, 6 (33%) underwent radiotherapy in the following years, owing to an increase in the volume of the remnants, and six (33%) underwent additional surgical treatment, followed by radiotherapy for further signs of growth in two. In the remaining patients, a small intrasellar remnant was stable on yearly MRI. CONCLUSIONS: in elderly patients, the development of hypopituitarism is often overlooked and the initial diagnosis of NFPM may be delayed. This can expose patients to the risks of unrecognized hypopituitarism and jeopardize post-surgical outcome.

Primary hyperparathyroidism and neuropsychiatric alterations in a nonagenarian woman.

Whether elderly patients with asymptomatic or minimally symptomatic primary hyperparathyroidism (PHPT) should be treated or not is still under debate. Several literature reports have shown improvements in terms of bone density and physical and mental well-being after surgical resolution of PHPT. Here, we present the case of a 93-year-old hypertensive woman, who had suffered for one year from cognitive impairment, accompanied during the last month by behavioral alterations (and polyuria and polydipsia), which resulted in sopor leading to hospitalization. A CT brain scan evidenced cortical atrophy and cerebrovascular disease, and biochemical analyses were remarkable for hypercalcemia (11.4-12.6 mg/dL, corrected for albumin levels) associated with increased parathormone levels (95.4-100.6 pg/mL). A diagnosis of PHPT was established. Densitometry evaluation of radius showed osteopenia. Withdrawal of psycho-therapy drugs and thiazidic, together with i.v. saline hydration and loop diuretics, significantly improved the patient's mental state and resolved behavioral alterations. As the patient and her relatives refused the surgical option, and the clinical situation improved after medical normalization of calcium levels, PHPT was managed conservatively, and calcium levels were maintained within the normal range through i.v. administration of zoledronate at 8-week intervals. Our case highlights the importance of considering hypercalcemia as the cause of onset of behavioral alterations and worsening of mental condition in elderly patients with cognitive decline. Therapy with bisphosphonates in patients with PHPT who are unfit for or refuse surgery seems advisable, but needs further study.

Thyroid storm as precipitating factor in onset of coma in an elderly woman: case report and literature review.

Thyroid storm is an uncommon but life-threatening manifestation of hyperthyroidism which, unless appropriately treated by combined therapy, causes 30-60% of deaths in hospitalized patients. Mental deterioration leading to apathy and eventually coma is a rare clinical presentation of this pathology, frequently observed in the elderly. We present the case of a 77-year-old hypertensive woman who was hospitalized for fast onset of coma, probably due to the unusual combination of a hypernatremic hyperosmolar state and an unexpected thyroid storm (TS). Although not definitely ascertained, the possible etiology was the hyperthyroid phase of chronic autoimmune thyreopathy (Hashitoxicosis). Notably, the significant adjunctive role of thyroid hyperfunction in the pathogenesis of coma was confirmed by the fact that, although metabolic abnormalities were overcome, complete and satisfactory recovery of the patient's mental and physical condition occurred only with normalization of thyroid hormones by antithyroid treatment. Our case highlights the importance of properly evaluating thyroid function in elderly patients who show a sudden progressive impairment in their mental condition, for early detection of potentially fatal conditions such as thyroid storm or myxedematous coma.

Adrenal gland hypofunction in active polymyalgia rheumatica. effect of glucocorticoid treatment on adrenal hormones and interleukin 6.

OBJECTIVE: To evaluate hypothalamic-pituitary-adrenal (HPA) axis function in patients with recent onset polymyalgia rheumatica (PMR) not previously treated with glucocorticoids; and to detect possible correlations between adrenal hormone levels, interleukin 6 (IL-6), and other acute phase reactants at baseline and during 12 months of glucocorticoid treatment. METHODS: Forty-one PMR patients of both sexes with recent onset disease and healthy sex and age matched controls were enrolled into a longitudinal study. Patients were monitored for serum cortisol, dehydroepiandrosterone sulfate (DHEAS), androstenedione (ASD), and clinical and laboratory measures of disease activity such as C-reactive protein and IL-6 concentrations at baseline and after 1, 3, 6, 9 and 12 months of glucocorticoid treatment. To assess dynamic HPA axis function, serum cortisol and plasma adrenocorticotropic hormone (ACTH) levels were evaluated in another 8 patients with recent onset PMR not treated with glucocorticoid in comparison to controls after challenge with ovine corticotropin releasing hormone (oCRH) test. In addition, serum cortisol and 17-hydroxyprogesterone (17-OHP) levels were evaluated after stimulation with low dose (1 microg) intravenous ACTH. RESULTS: Serum cortisol and ASD levels of all PMR patients at baseline did not differ from controls. During followup, cortisol levels dipped at one and 3 months. Serum DHEAS levels in all patients were significantly lower than in controls at baseline. In female PMR patients a significant correlation was found at baseline between cortisol levels and duration of disease. Serum concentrations of IL-6 at baseline were significantly higher in PMR patients than in controls. During 12 months of glucocorticoid treatment IL-6 levels dropped significantly at one month; thereafter they remained stable and did not increase again despite tapering of the glucocorticoid dose. After oCRH stimulation, a similar cortisol response was found in patients and controls. After ACTH administration, a significant cortisol peak was detected in patients and controls, whereas no significant difference in cortisol area-under-the-curve (AUC) was found between the groups. In contrast, ACTH induced a significantly higher (p < 0.05) peak of 17-OHP and AUC in PMR patients than in controls. CONCLUSION: This study found reduced production of adrenal hormones (cortisol, DHEAS) at baseline in patients with active and untreated PMR. The defect seems mainly related to altered adrenal responsiveness to the ACTH stimulation (i.e., increased 17-OHP), at least in untreated patients. The 12 month glucocorticoid treatment of patients reduced the production of inflammatory mediators (i.e., IL-6) in a stable manner that persisted after glucocorticoids were tapered.