The key role of depression and supramarginal gyrus in frailty: a cross-sectional study.

Background: The age-related decrease in reserve and resistance to stressors is recognized as frailty, one of the most significant challenges identified in recent years. Despite a well-acknowledged association of frailty with cognitive impairment, depression, and gray matter morphology, no clear data are available regarding the nature of this relationship. This cross-sectional study aims to disentangle the role of the behavioral, neuropsychological, and neural components as predictors or moderators of frailty. Methods: Ninety-six older adults (mean age = 75.49 ± 6.62) were consecutively enrolled and underwent a clinical and MRI (3 T) evaluation to assess frailty, physical activity, global cognitive level, depression, wellbeing, autonomy in daily living, cortical thickness, and subcortical volumes. Results: Results showed a full mediation of depression on the link between cortical thickness and frailty, while the cognitive level showed no significant mediating role. In particular, left supramarginal thickness had a predicting role on depression, that in turn impacted frailty occurrence. Finally, handgrip weakness was an early key indicator of frailty in this study's cohort. Conclusion: These data substantiate the role of depression in mediating the link between neural integrity of the supramarginal gyrus and frailty. In the complexity of frailty, handgrip weakness seems to be an early key indicator. These results are relevant for the design of rehabilitation interventions aimed at reversing the frail condition.

Technologies for frailty, comorbidity, and multimorbidity in older adults: a systematic review of research designs.

BACKGROUND: Frailty, neurodegeneration and geriatric syndromes cause a significant impact at the clinical, social, and economic level, mainly in the context of the aging world. Recently, Information and Communication Technologies (ICTs), virtual reality tools, and machine learning models have been increasingly applied to the care of older patients to improve diagnosis, prognosis, and interventions. However, so far, the methodological limitations of studies in this field have prevented to generalize data to real-word. This review systematically overviews the research designs used by studies applying technologies for the assessment and treatment of aging-related syndromes in older people. METHODS: Following the PRISMA guidelines, records from PubMed, EMBASE, and Web of Science were systematically screened to select original articles in which interventional or observational designs were used to study technologies' applications in samples of frail, comorbid, or multimorbid patients. RESULTS: Thirty-four articles met the inclusion criteria. Most of the studies used diagnostic accuracy designs to test assessment procedures or retrospective cohort designs to build predictive models. A minority were randomized or non-randomized interventional studies. Quality evaluation revealed a high risk of bias for observational studies, while a low risk of bias for interventional studies. CONCLUSIONS: The majority of the reviewed articles use an observational design mainly to study diagnostic procedures and suffer from a high risk of bias. The scarce presence of methodologically robust interventional studies may suggest that the field is in its infancy. Methodological considerations will be presented on how to standardize procedures and research quality in this field.

Differential Roles of Neural Integrity, Physical Activity and Depression in Frailty: Sex-Related Differences.

The frailty sex paradox has recently gained attention. At all ages, females are more likely to be frail and show a more severe phenotype but have a higher survival rate compared to males. The main aim was to test sex-specific differences in frailty syndrome using a multimodal evaluation from clinical and imaging data to deepen the understanding of different underlying mechanisms involved in the two sexes, and thus understand the association with different risk factors. Ninety-six community-dwelling older adults were characterized by clinical underpinnings (Fried's frailty indicators: comorbidity, depression, global cognitive level, physical activity, autonomy), and neural integrity (T1-weighted brain 3T MRI). The frailty × sex interaction in clinical and neural profiles was tested. Additionally, frailty risk factors were identified in the two sexes separately. Results showed that fragility was associated with an increment of depressive symptomatology in females, while a decrement in physical activity was observed already in the pre-frail stage in males. Finally, different risk factors were observed in the two groups: significant frailty predictors were neural integrity and physical activity in males, and age and depression in females. These data support the starting hypothesis of at least partially different mechanisms involved in the frailty phenotype between men and women.

Signs and symptoms method in neuropsychology: A standardized observational examination of cognitive functions can be effective in detecting mild cognitive impairment.

OBJECTIVE: The present study aimed at investigating the sensitivity and specificity of the NeuroPsychological Examination (NPE), a systematic collection of cognitive signs and symptoms based on the observation of the patient's behavior during a clinical interview, in detecting Mild Cognitive Impairment (MCI). METHOD: 475 participants, 208 suffering from MCI, 188 suffering from dementia and 79 subjective cognitive decline (SCD), have been assessed using NPE for the presence of signs and symptoms of cognitive impairment. Receiver operating characteristic (ROC) curve analysis and the Youden's test were used to determine the more appropriate cutoff points for the number of neuropsychological signs at the NPE that enabled to discriminate SCD from MCI, SCD from dementia and MCI from dementia. A sensitivity and specificity analysis and comparisons among the three groups were conducted. RESULTS: The mean number of signs at the NPE were 1.73 for SCD, 7.98 for MCI and 12.82 for dementia. Pairwise comparisons among the three group of participants showed significant differences (SCD vs. MCI, p < .001, r = -0.66; SCD vs. dementia, p < .001, r = -0.76; MCI vs. dementia, p < .001, r = -0.44). The criterion of 3 signs at the NPE showed a sensitivity of 0.95 (95% CI [0.91, 0.97]) and a specificity of 0.76 (95% CI [0.65, 0.84]) in discriminating SCD from MCI participants. CONCLUSIONS: A signs and symptoms approach could be a useful tool for clinical neuropsychologists working in the field of MCI and dementia assessment. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Diencephalic versus Hippocampal Amnesia in Alzheimer's Disease: The Possible Confabulation-Misidentification Phenotype.

BACKGROUND: Alzheimer's disease (AD) is clinically heterogeneous, including the classical-amnesic (CA-) phenotype and some variants. OBJECTIVE: We aim to describe a further presentation we (re)named confabulation-misidentification (CM-) phenotype. METHODS: We performed a retrospective longitudinal case-series study of 17 AD outpatients with the possible CM-phenotype (CM-ADs). Then, in a cross-sectional study, we compared the CM-ADs to a sample of 30 AD patients with the CA-phenotype (CA-ADs). The primary outcome was the frequency of cognitive and behavioral features. Data were analyzed as differences in percentage by non-parametric Chi Square and mean differences by parametric T-test. RESULTS: Anterograde amnesia (100%) with early confabulation (88.2%), disorientation (88.2%) and non-infrequently retrograde amnesia (64.7%) associated with reduced insight (88.2%), moderate prefrontal executive impairment (94.1%) and attention deficits (82.3%) dominated the CM-phenotype. Neuropsychiatric features with striking misidentification (52.9%), other less-structured delusions (70.6%), and brief hallucinations (64.7%) were present. Marked behavioral disturbances were present early in some patients and very common at later stages. At the baseline, the CM-ADs showed more confabulation (p < 0.001), temporal disorientation (p < 0.02), misidentification (p = 0.013), other delusions (p = 0.002), and logorrhea (p = 0.004) than the CA-ADs. In addition, more social disinhibition (p = 0.018), reduction of insight (p = 0.029), and hallucination (p = 0.03) persisted at 12 months from baseline. Both the CA- and CM-ADs showed anterior and medial temporal atrophy. Compared to HCs, the CM-ADs showed more right fronto-insular atrophy, while the CA-ADs showed more dorsal parietal, precuneus, and right parietal atrophy. CONCLUSION: We described an AD phenotype resembling diencephalic rather than hippocampal amnesia and overlapping the past-century description of presbyophrenia.

Mortality and characteristics of older people dying with COVID-19 in Lombardy nursing homes, Italy: An observational cohort study.

BACKGROUND: The aim of the study was to describe the epidemiological characteristics of Nursing Homes (NHs) residents infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and to compute the related case-fatality rate. MATERIALS AND METHODS: The outcomes were mortality and case-fatality rate with related epidemiological characteristics (age, sex, comorbidity, and frailty). RESULTS: During the COVID-19 outbreak lasted from March 1 to May 7, 2020, 330 residents died in Fondazione Don Gnocchi NHs bringing the mortality rate to 27% with a dramatic increase compared to the same period of 2019, when it was 7.5%. Naso/oropharyngeal swabs resulted positive for COVID-19 in 315 (71%) of the 441of the symptomatic/exposed residents tested. The COVID-19 population was 75% female, with a 17% overall fatality rate and sex-specific fatality rates of 19% and 13% for females and males, respectively. Fifty-six percent of deaths presented SARS-CoV-2-associated pneumonia, 15% cardiovascular, and 29% miscellaneous pathologies. CONCLUSION: Patients' complexity and frailty might influence SARS-CoV-2 infection case-fatality rate estimates. A COVID-19 register is needed to study COVID-19 frail patients' epidemiology and characteristics.

ICT technologies as new promising tools for the managing of frailty: a systematic review.

OBJECTIVES: Frailty is a major health issue as it encompasses functional decline, physical dependence, and increased mortality risk. Recent studies explored Information and Communication Technology (ICT) interventions as alternatives to manage frailty in older persons. The aim of the present systematic review was to synthesize current evidence on ICT application within the complex models of frailty care in older people. METHODS: Data sources included PubMed, PsycINFO, EMBASE and Web of Science, considering eligible those reviews on ICT application in samples of older persons formally assessed as frail. Records were screened by two independent researchers, who extracted data and appraised methodological quality of reviews and studies. RESULTS: Among the 764 retrieved papers, two systematic reviews were included. Most of the studies analyzed defined frailty considering only few components of the phenotype and used ICT to stratify different levels of frailty or to support traditional screening strategies. Assessment of frailty was the context in which ICT has been mostly tested as compared to intervention. Cost effectiveness evaluations of the ICT technologies were not reported. CONCLUSIONS: The research investigating the use of ICT in the context of frailty is still at the very beginning. Few studies strictly focused on the assessment of frailty, while intervention on frailty using ICT was rarely reported. The lack of a proper characterization of the frail condition along with the methodological limitations prevented the investigation of ICT within complex care models. Future studies are needed to effectively integrate ICT in the care of frailty in orders.

Signs and symptoms method in neuropsychology: A preliminary investigation of a standardized clinical interview for assessment of cognitive decline in dementia.

Psychologists usually perform a preliminary assessment of the person's cognitive status through a brief interview conducted before the formal testing. However, this exam has not yet been standardized with ad hoc recommendations in psychology literature. In this work, a standard observational NeuroPsychological Examination (NPE) designed for psychologists was proposed, and its clinical effectiveness evaluated. The NPE was administered to patients referred to a neuropsychological service in a memory clinic over a 2-year period. The NPEs of the patients with Alzheimer dementia (AD), vascular dementia (VaD), and healthy controls (HC) were retrospectively retrieved. Comparisons among the three groups were conducted. Abnormalities/signs identified during the NPE in the AD and VaD groups are more numerous compared to those reported in the HC group. About 80% of HCs show none or only one abnormal sign. Vice versa, 87.5% of both AD and VaD patients show three or more abnormalities. Accordingly, the NPE has 0.88 (95%CI = 0.81-0.95) sensitivity and 0.95 (95%CI = 0.88-1.02) specificity for detecting cognitive decline when a cut-point of three or more signs is applied. Some significant differences also emerge on the number of pathological signs between AD and VaD patients. NPE is a promising tool with demonstrated diagnostic utility in dementia patients.

Usability Issues of Clinical and Research Applications of Virtual Reality in Older People: A Systematic Review.

Aging is a condition that may be characterized by a decline in physical, sensory, and mental capacities, while increased morbidity and multimorbidity may be associated with disability. A wide range of clinical conditions (e.g., frailty, mild cognitive impairment, metabolic syndrome) and age-related diseases (e.g., Alzheimer's and Parkinson's disease, cancer, sarcopenia, cardiovascular and respiratory diseases) affect older people. Virtual reality (VR) is a novel and promising tool for assessment and rehabilitation in older people. Usability is a crucial factor that must be considered when designing virtual systems for medicine. We conducted a systematic review with Preferred Reporting Items for Systematic reviews and Meta-analysis (PRISMA) guidelines concerning the usability of VR clinical systems in aging and provided suggestions to structure usability piloting. Findings show that different populations of older people have been recruited to mainly assess usability of non-immersive VR, with particular attention paid to motor/physical rehabilitation. Mixed approach (qualitative and quantitative tools together) is the preferred methodology; technology acceptance models are the most applied theoretical frameworks, however senior adapted models are the best within this context. Despite minor interaction issues and bugs, virtual systems are rated as usable and feasible. We encourage usability and user experience pilot studies to ameliorate interaction and improve acceptance and use of VR clinical applications in older people with the aid of suggestions (VR-USOP) provided by our analysis.

The last week of life of nursing home residents with advanced dementia: a retrospective study.

BACKGROUND: Barriers to palliative care still exist in long-term care settings for older people, which can mean that people with advanced dementia may not receive of adequate palliative care in the last days of their life; instead, they may be exposed to aggressive and/or inappropriate treatments. The aim of this multicentre study was to assess the clinical interventions and care at end of life in a cohort of nursing home (NH) residents with advanced dementia in a large Italian region. METHODS: This retrospective study included a convenience sample of 29 NHs in the Lombardy Region. Data were collected from the clinical records of 482 residents with advanced dementia, who had resided in the NH for at least 6 months before death, mainly focusing on the 7 days before death. RESULTS: Most residents (97.1%) died in the NH. In the 7 days before death, 20% were fed and hydrated by mouth, and 13.4% were tube fed. A median of five, often inappropriate, drugs were prescribed. Fifty-seven percent of residents had an acknowledgement of worsening condition recorded in their clinical records, a median of 4 days before death. CONCLUSIONS: Full implementation of palliative care was not achieved in our study, possibly due to insufficient acknowledgement of the appropriateness of some drugs and interventions, and health professionals' lack of implementation of palliative interventions. Future studies should focus on how to improve care for NH residents.

Does the Right Focal Variant of Alzheimer's Disease Really Exist? A Literature Analysis.

BACKGROUND: Alzheimer's disease (AD) is a clinically heterogeneous disease. Multiple atypical syndromes, distinct from the usual amnesic phenotype, have been described. In this context, the existence of a right variant of AD (RAD), characterized by enduring visuospatial impairment associated with right-sided asymmetric brain damage, has been proposed. However, to date, this phenotype remains controversial. In particular, its peculiar characteristics and the independence from more prevalent cases (especially the posterior cortical atrophy syndrome) have to be demonstrated. OBJECTIVE: To explore the existence of focal RAD on the basis of existing literature. METHODS: We performed a literature search for the description of atypical AD presentations, potentially evoking cases of focal RAD. To be considered as affected by RAD, the described cases had to present: 1) well documented right-sided asymmetry at neuroimaging; 2) predominant cognitive deficits localizable on the right hemisphere; 3) no specific diagnosis of a known variant of AD. RESULTS: Twenty-one cases were found in the literature, but some of them were subsequently excluded because some features of a different clinical syndrome were overlapped with the clinical features of RAD. Thirteen positive cases, three of them with pathologically confirmed AD, remained. A common right clinical-radiological syndrome, characterized by memory and visuospatial impairment with temporal and parietal involvement, consistently emerged. However, the heterogeneity among the reports prevented a definitive and univocal description of the syndrome. CONCLUSION: Even if sporadic observations strongly support the existence of a focal RAD, no definitive conclusions can still be drawn about it as an independent condition.

The Impact of Nursing Homes Staff Education on End-of-Life Care in Residents With Advanced Dementia: A Quality Improvement Study.

CONTEXT: End-of-life care in nursing homes (NHs) needs improvement. We carried out a study in 29 NHs in the Lombardy Region (Italy). OBJECTIVES: The objective of this study was to compare end-of-life care in NH residents with advanced dementia before and after an educational intervention aimed to improving palliative care. METHODS: The intervention consisted of a seven-hour lecture, followed by two 3-hour meetings consisting of case discussions. The intervention was held in each NH and well attended by NH staff. This multicenter, comparative, observational study included up to 20 residents with advanced dementia from each NH: the last 10 who died before the intervention (preintervention group, 245 residents) and the first 10 who died at least three months after the intervention (postintervention group, 237 residents). Data for these residents were collected from records for 60 days and seven days before death. RESULTS: The use of "comfort hydration" (<1000 mL/day subcutaneously) tended to increase from 16.9% to 26.8% in the postintervention group. The number of residents receiving a palliative approach for nutrition and hydration increased, though not significantly, from 24% preintervention to 31.5% postintervention. On the other hand, the proportion of tube-fed residents and residents receiving intravenous hydration decreased from 15.5% to 10.5%, and from 52% to 42%, respectively. Cardiopulmonary resuscitations decreased also from 52/245 (21%) to 18/237 (7.6%) cases (P = 0.002). CONCLUSION: The short educational intervention modified some practices relevant to the quality of end-of-life care of advanced dementia patients in NHs, possibly raising and reinforcing beliefs and attitudes already largely present.

Evidence of altered pressure pain thresholds in persons with disorders of consciousness as measured by the Nociception Coma Scale-Italian version.

Pain assessment in patients with disorders of consciousness (DoC) is a controversial issue for clinicians, who require tools and standardised procedures for testing nociception in non-communicative patients. The aims of the present study were, first, to analyse the psychometric properties of the Italian version of the Nociception Coma Scale and, second, to evaluate pressure pain thresholds in a group of patients with DoC. The authors conducted a multi-centre study on 40 healthy participants and 60 DoC patients enrolled from six hospitals in Italy. For each group an electronic algometer was used to apply all nociceptive pressure stimuli. Our results show that the Italian version of the NCS retains the good psychometric properties of the original version and is therefore suitable for standardised pain assessment in clinical practice. In our study, pressure pain thresholds measured in a group of patients in vegetative and minimally conscious state were relatively lower than pain threshold values found in a group of healthy participants. Such findings motivate additional investigation on possible pain sensitisation in patients with severe brain injury and multiple co-morbidities, and on application of tailored therapeutic approaches useful for pain management in patients unable verbally to communicate their feelings.

Pneumonia in Nursing Home Patients With Advanced Dementia: Decisions, Intravenous Rehydration Therapy, and Discomfort.

BACKGROUND: Comfort may be an appropriate goal in advanced dementia. Longitudinal studies on physician decision-making and discomfort assessed by direct observation are rare, and intravenous rehydration therapy is controversial. METHODS: To assess treatment decisions and discomfort in patients with advanced dementia and pneumonia and to compare by intravenous rehydration therapy, we used data from the observational multicenter Italian End of Life Observatory-Prospective Study On DEmentia patients Care. We analyzed 109 episodes of pneumonia, which involved decisions in 77 nursing home patients with Functional Assessment Staging Tool stage 7. We assessed decisions, decision-making, and treatments every fortnight. Trained observers assessed discomfort with the Discomfort Scale-Dementia Alzheimer Type (DS-DAT). RESULTS: Most decisions referred to treatment with antibiotics (90%; 98 of 109) and intravenous rehydration therapy (53%; 58 of 109), but hospitalization was rare (1%). Selecting decisions with antibiotics, with rehydration therapy, the prognosis was more frequently <15 days (34% vs 5% without rehydration therapy; P = .001), and a goal to reduce symptoms/suffering was more common (96% vs 74%; P = .005) while there was no difference in striving for life prolongation (a minority). With rehydration therapy, the decision was more often discussed with family rather than communicated only. Mean DS-DAT scores over time proximate to the first decision ranged between 9.2 and 10.5. CONCLUSIONS: Italian nursing home patients with advanced dementia and pneumonia frequently received invasive rehydration therapy in addition to antibiotics, however, mostly with a palliative intent. Discomfort was high overall and symptom relief may be improved. Relations between invasive rehydration therapy and discomfort need further study.

Familial late-onset Alzheimer's disease: description of an Italian family with four affected siblings and one case of early-onset dementia in the preceding generation.

We describe a family composed of six siblings, four of which affected by late-onset Alzheimer's disease (LOAD). We constructed the family pedigree, evaluated mutations usually associated with early-onset Alzheimer's disease (APP, PSEN1, PSEN2), and assessed polymorphisms in the apolipoprotein E (APOE) gene and in cytokine genes that we had previously found to be associated with a higher risk of LOAD (IL-10, IL-6, TNF-α). Results showed that all subjects carried one ε4 allele of the APOE gene and those with the earliest age of onset exhibited the AA (-1082) IL-10 and the CC (-174) IL-6 genotypes. The only male had a genetic profile which also included the A (-308) TNF-α allele. These data confirm the role of the APOE gene as genetic risk factor in LOAD, and suggest that the risk of developing AD may be governed by a "susceptibility profile" involving polymorphisms in inflammatory genes.

Critical decisions for older people with advanced dementia: a prospective study in long-term institutions and district home care.

OBJECTIVE: To describe and compare the decisions critical for survival or quality of life [critical decisions (CDs)] made for patients with advanced dementia in nursing homes (NHs) and home care (HC) services. DESIGN: Prospective cohort study with a follow-up of 6 months. SETTING: Lombardy Region (NHs) and Reggio-Emilia and Modena Districts (HC), Italy. PARTICIPANTS: Patients (496 total; 315 in NHs and 181 in HC) with advanced dementia (Functional Assessment Staging Tool score ≥ 7) and expected survival ≥ 2 weeks. MEASUREMENTS: At baseline, the patients' demographic data, date of admission and of dementia diagnosis, type of dementia, main comorbidities, presence of pressure sores, ongoing treatments, and current prescriptions were abstracted from clinical records. At baseline and every 15 days thereafter, information regarding the patients' general condition and CDs (deemed critical by the doctor or team) was collected by an interview with the doctor. For each CD, the physician reported the problem that led to the decision, that was eventually made, the purpose of the decision, whether the decision had been discussed with and/or communicated to the family, who made the final decision, whether the decision was maintained after 1 week, whether it corresponded to what the doctor would have judged appropriate, and the expected survival of the patient (≤ 15 days). RESULTS: For 267 of the 496 patients (53.8%; 60.3% in NHs and 42.5% at home), 644 CDs were made; for 95 patients, more than 1 CD was made. The problems that led to a CD were mainly infections (respiratory tract and other infections; 46.6%, 300/644 CDs); nutritional/hydration problems (20.6%; 133 CDs); and the worsening of a pre-existing disease (9.3%; 60 CDs). The most frequent type of decision concerned the prescription of antibiotics (overall 41.1%, 265/644; among NH patients 44.6%, 218/488; among HC patients, 30.2%, 47/156). The decision to hospitalize the patient was more frequently reported for HC than NH patients (25.5% vs 3.1%). The most frequent purposes of the CDs in both settings were reducing symptoms or suffering (more so in NHs; 81.1% vs 57.0% in HC) and prolonging survival (NH 27.5%; HC 23.1%; multiple purposes were possible). For 26 decisions (3.8%), the purpose was to ease death or not to prolong life. CONCLUSIONS: Decisions critical for the survival or quality of life of patients with advanced dementia were made for approximately one-half of the patients during a 6-month time frame, and such decisions were made more frequently in NHs than in HC. HC patients were more frequently hospitalized, and a sizeable minority of these patients were treated with the goal of prolonging survival. Italian patients with advanced dementia may benefit from the implementation of palliative care principles, and HC patients may benefit from the implementation of measures to avoid hospitalizing patients near the end of life.