Addressing relationship quality of people with dementia and their family carers: which profiles require most support?

Objective: The quality of the relationship between persons with dementia and family carers influences health and quality-of-life outcomes. Little is known regarding those at higher risk of experiencing a decline in relationship quality, who could potentially benefit the most from interventions. We aimed to identify these risk profiles and explore the underlying factors. Methods: We applied a latent profile analysis to relationship quality data from a 1-year follow-up of 350 dyads of persons with dementia and their informal carers from the Actifcare cohort in eight European countries. Assessments included sociodemographic, clinical, functional, psychosocial and quality-of-life measures. Relationship quality was assessed with the Positive Affect Index. A discriminant analysis explored factors influencing the risk profiles. Results: There were two relationship quality profiles among persons with dementia (gradually decreasing, 74.0%; low but improving, 26%) and two among carers (steadily poor, 57.7%; consistently positive, 42.3%). The 'gradually decreasing' profile (persons with dementia) was related to their levels of dependence and unmet needs, along with carers' social distress and negative feelings, lower baseline RQ and sense of coherence. The 'steadily poor' profile (carers) was influenced by their social distress and negative feelings, lower sense of coherence and perceived social support. These two predominant profiles showed significant decreases in quality-of-life over one year. Conclusions: Specific profiles of persons with dementia and their carers are at risk of worse relationship quality trajectories. By considering modifiable related factors (e.g., carers' stress), our findings can help develop tailored, effective interventions.

Virtual Reality Combined With Psychoeducation to Improve Emotional Well-Being in Informal Caregivers of Alzheimer's Disease Patients: Rationale and Study Design of a Randomized Controlled Trial.

OBJECTIVES: Care for community-dwelling people with dementia is frequently delegated to relatives, who find themselves in the role of informal caregivers with no practical management knowledge. This situation exposes caregivers to increased risk for emotional wellbeing. The current study aims to test whether the integration of the efficacy of an immersive virtual reality (VR) experience into an online psychoeducational program impacts caregiver empathy and therefore emotional wellbeing. METHODS: One-hundred informal caregivers of mild-to-moderate Alzheimer's disease (AD) patients will be enrolled and randomly assigned to (i) an online psychoeducational program (control arm); or (ii) an online psychoeducational program integrated with VR (experimental arm). VR will consist of 360-degree videos involving the caregivers to an immersive experience of dementia symptoms from the patient's perspective. Before, after the intervention and after 2 months, all participants will complete validated clinical scales for caregiver burden and anxiety (primary outcomes) and sense of competence and dispositional empathy (secondary outcomes). A subsample of 50 participants will also undergo MRI exam, including structural and functional (resting-state and task-functional MRI [fMRI]) sequences. The fMRI task paradigm will use emotional stimuli to evaluate the neural correlate of empathy, by stressing its cognitive and affective components. The main outcome will be the change in the clinical assessment; the secondary outcome will be the change in brain connectivity of networks subserving the empathic and emotional functioning. RESULTS: We expect that the psychoeducational program will decrease anxiety and stress, enabling caregivers to perceive themselves capable of managing AD patients at home, educating them on symptom handling and boosting their cognitive empathy. In the experimental intervention, the VR-based experience will act as an add-on to psychoeducation, leading to greater improvement in the assessed clinical dimensions. VR should, in fact, enable a deeper understanding of disease symptoms and improve caregivers' cognitive empathy. We expect that the experimental intervention will result in deeper comprehension of disease symptoms and further strengthen caregivers' cognitive empathy. At the neural level, we expect to observe increased activation in circuits subserving cognitive empathy and decreased activation in circuits underlying affective empathy. CONCLUSIONS: To the best of our knowledge, this will be the first randomized controlled trial assessing the effect of combining psychoeducational interventions with VR-based experience in caregivers, and assessing both clinical and imaging outcomes. TRIAL REGISTRATION: Registered in ClinicalTrials.gov (NCT05780476).

Serum Beta-Secretase 1 Activity Is a Potential Marker for the Differential Diagnosis between Alzheimer's Disease and Frontotemporal Dementia: A Pilot Study.

Alzheimer's disease (AD) and frontotemporal dementia (FTD) are the two major neurodegenerative diseases causing dementia. Due to similar clinical phenotypes, differential diagnosis is challenging without specific biomarkers. Beta-site Amyloid Precursor Protein cleaving enzyme 1 (BACE1) is a ß-secretase pivotal in AD pathogenesis. In AD and mild cognitive impairment subjects, BACE1 activity is increased in brain/cerebrospinal fluid, and plasma levels appear to reflect those in the brain. In this study, we aim to evaluate serum BACE1 activity in FTD, since, to date, there is no evidence about its role. The serum of 30 FTD patients and 30 controls was analyzed to evaluate (i) BACE1 activity, using a fluorescent assay, and (ii) Glial Fibrillary Acid Protein (GFAP) and Neurofilament Light chain (NfL) levels, using a Simoa kit. As expected, a significant increase in GFAP and NfL levels was observed in FTD patients compared to controls. Serum BACE1 activity was not altered in FTD patients. A significant increase in serum BACE1 activity was shown in AD vs. FTD and controls. Our results support the hypothesis that serum BACE1 activity is a potential biomarker for the differential diagnosis between AD and FTD.

Psychobiological effects of an eHealth psychoeducational intervention to informal caregivers of persons with dementia: a pilot study during the COVID-19 pandemic in Italy.

BACKGROUND: The workload associated with caring for a person with dementia (PwD) could negatively affect informal caregivers' physical and mental health. According to the recent literature, there is a need for studies testing the implementation of affordable and accessible interventions for improving caregivers' well-being. AIMS: This study aimed to explore the feasibility and effectiveness of an 8 week eHealth psychoeducation intervention held during the COVID-19 pandemic in Italy in reducing the psychological burden and neuroendocrine markers of stress in caregivers of PwD. METHODS: Forty-one informal caregivers of PwD completed the eHealth psychoeducation intervention. Self-reported (i.e., caregiver burden, anxiety symptoms, depressive symptoms, and caregiver self-efficacy) and cortisol measurements were collected before and after the intervention. RESULTS: Following the intervention, the caregivers' self-efficacy regarding the ability to respond to disruptive behaviours improved (t = - 2.817, p = 0.007), anxiety and burden levels decreased (state anxiety: t = 3.170, p = 0.003; trait anxiety: t = 2.327, p = 0.025; caregiver burden: t = 2.290, p = 0.027), while depressive symptoms and cortisol levels did not change significantly. Correlation analyses showed that the increase in self-efficacy was positively associated with the improvement of caregiver burden from pre- to post-intervention (r = 0.386, p = 0.014). The intervention had a low rate of dropout (n = 1, due to the patient's death) and high levels of appreciation. DISCUSSION: The positive evidence and participation rate support the feasibility and effectiveness of the proposed eHealth psychoeducational intervention to meet the need for knowledge of disease management and possibly reduce detrimental effects on caregivers' psychological well-being. CONCLUSION: Further placebo-controlled trials are needed to test the generalizability and specificity of our results.

Treating depression in clinical practice: new insights on the multidisciplinary use of trazodone.

Depression is estimated to be a leading contributor to the global mental health-related burden. The determinants of this huge prevalence lie in the fact that depressive symptoms may be comorbid in a wide variety of disorders, thus complicating and exacerbating their clinical framework. This makes the treatment of depressive symptoms difficult, since many pharmacological interactions should be considered by physicians planning therapy. Hence, depression still represents a challenge for both psychiatrists and other clinicians, in terms of its high rates of relapse and resistance despite well-established protocols. It is also complicated by the well-known latency in its complete response to current antidepressant treatments. In this context, the search for new strategies regarding antidepressant treatment is mandatory. Revising the use of "old" pharmacotherapies by considering their specific features may help to perfecting the treatment of depression, both in its standalone psychiatric manifestation and in the framework of other clinical conditions. Using a nominal group technique approach, the results of a consensus of expert physicians regarding the possible use of trazodone as a valuable strategy for addressing the "real world" unmet needs of depression treatment in different fields (psychiatry, primary care, neurology and geriatrics) is herein provided. This idea is based on the unique characteristics of this drug which delivers a more rapid antidepressant action as compared to other selective serotonin reuptake inhibitors. It also has pharmacodynamic malleability (i.e., the possibility of exerting different effects on depressive symptoms at different dosages) and pharmacokinetic tolerability (i.e., the possibility of being used as an add-on to other antidepressants with scarce interaction and achieving complimentary effects) when used in the milieu of other drugs in treating comorbid depressive symptoms. Moreover, the large number of formulations available permits finite dosage adjustments, and the use of trazodone for specific pathologies, such as dysphagia. Therefore, although additional studies exploring the real-world conditions of antidepressant treatment are warranted, experts agree on the idea that depressive disorder, in both its standalone and its comorbid manifestations, may surely take advantage of the particular characteristics of trazodone, thus attempting to reach the greatest effectiveness in different contexts.

Disclosure of Genetic Risk Factors for Alzheimer's Disease to Cognitively Healthy Individuals-From Current Practice towards a Personalised Medicine Scenario.

Alzheimer's disease (AD) is a genetically complex disorder. In addition to the relatively small number of pathogenic variants causing autosomal dominant AD, many others have been associated with the much more common sporadic form. The E4 allele of the Apolipoprotein E (APOE) is the first discovered genetic risk factor for AD. In addition, more than 70 genetic risk loci contributing to AD have been identified. Current guidelines do not recommend AD susceptibility genetic testing in cognitively healthy adults because the implications for clinical care are limited. However, secondary prevention clinical trials of disease-modifying therapies enrol individuals based on genetic criteria, and participants are often informed of APOE testing results. Moreover, the availability of direct-to-consumer genetic testing allows individuals to learn their own AD genetic risk profile without medical supervision. A number of research protocols for AD susceptibility genetic testing have been proposed. In Italy, disclosure processes and protocols beyond those developed for inherited dementia have not been established yet. We reviewed the literature on the current practice and clinical issues related to disclosing AD genetic risk to cognitively healthy individuals and provide suggestions that may help to develop specific guidelines at the national level.

The new therapy for Alzheimer's disease: from a hope for a few to a false hope?

Since the late ninety, research on Alzheimer's disease has been focused on the search of drugs able to modify the disease course. Patients and caregivers waiting for news on this topic, received enthusiastically the advice of the approval of Aducanumab-anti-amyloid ß monoclonal antibody-by the FDA, and that of its rejection by the EMA with even greater disappointment. To estimate the number of patients that we would be able to treat-hypothesizing a possible future approval by EMA- in the memory clinic of the IRCCS S. Giovanni di Dio FBF of Brescia, we analyzed 1561 patients undergone a first geriatric visit in January 1st to December 31st 2019. Applying the EMERGE and ENGAGE studies criteria, only 15 of them (1%) could be eligible for Aducanumab. The communication of scientific news should be transparent, more balanced and less sensationalistic, to avoid the rise of false hopes and consequent disillusionment.

Increased Serum Beta-Secretase 1 Activity is an Early Marker of Alzheimer's Disease.

BACKGROUND: Beta-site APP cleaving enzyme 1 (BACE1) is the rate-limiting enzyme in amyloid-ß (Aß) plaques formation. BACE1 activity is increased in brains of patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) and plasma levels of BACE1 appears to reflect those in the brains. OBJECTIVE: In this work, we investigated the role of serum BACE1 activity as biomarker for AD, estimating the diagnostic accuracy of the assay and assessing the correlation of BACE1 activity with levels of Aß1 - 40, Aß1 - 42, and Aß40/42 ratio in serum, known biomarkers of brain amyloidosis. METHODS: Serum BACE1 activity and levels of Aß1 - 40, Aß1 - 42, were assessed in 31 AD, 28 MCI, diagnosed as AD at follow-up (MCI-AD), and 30 controls. The BACE1 analysis was performed with a luciferase assay, where interpolation of relative fluorescence units with a standard curve of concentration reveals BACE1 activity. Serum levels of Aß1 - 40, Aß1 - 42 were measured with the ultrasensitive Single Molecule Array technology. RESULTS: BACE1 was increased (higher than 60%) in AD and MCI-AD: a cut-off of 11.04 kU/L discriminated patients with high sensitivity (98.31%) and specificity (100%). Diagnostic accuracy was higher for BACE1 than Aß40/42 ratio. High BACE1 levels were associated with worse cognitive performance and earlier disease onset, which was anticipated by 8 years in patients with BACE1 values above the median value (> 16.67 kU/L). CONCLUSION: Our results provide new evidence supporting serum/plasma BACE1 activity as an early biomarker of AD.

Brain network modulation in Alzheimer's and frontotemporal dementia with transcranial electrical stimulation.

The default mode (DMN) and the salience (SN) networks show functional hypo-connectivity in Alzheimer's disease (AD) and the behavioral variant of frontotemporal dementia (bvFTD), respectively, along with patterns of hyper-connectivity. We tested the clinical and neurobiological effects of noninvasive stimulation over these networks in 45 patients (AD and bvFTD) who received either anodal (target network: DMN in AD, SN in bvFTD) or cathodal stimulation (target network: SN in AD, DMN in bvFTD). We evaluated changes in clinical, cognitive, functional and structural connectivity, and perfusion measures. In both patient groups, cathodal stimulation was followed by behavioral improvement, whereas anodal stimulation led to cognitive improvement. Neither functional connectivity nor perfusion showed significant effects. A significant interaction between DMN and SN functional connectivity changes and stimulation protocol was reported in AD. These results suggest a protocol-dependent response, whereby the protocols studied show divergent effects on cognitive and clinical measures, along with a divergent modulatory pattern of connectivity in AD.

Trajectories of relationship quality in dementia: a longitudinal study in eight European countries.

OBJECTIVES: Relationship quality (RQ) between a person with dementia and a family carer may influence their health and quality of life. However, evidence regarding its course and influencing factors is limited. We aimed to explore RQ trajectories in dementia, and identify predictors of change. METHODS: We analysed longitudinal data from a cohort of 350 community-dwelling people with dementia and their informal carers, participating in the Actifcare study in eight European countries. The Positive Affect Index, rated separately by both people with dementia and their carers, assessed RQ. Other measures included the Neuropsychiatric Inventory Questionnaire (regarding persons with dementia), and the Relative Stress Scale, Sense of Coherence Scale and Lubben Social Network Scale (for carers). Trajectories and influencing factors were explored applying a latent growth model (LGM). RESULTS: RQ in the group of carers declined over 1 year, but RQ scores for the persons with dementia did not change. Higher stress in carers negatively influenced their baseline RQ ratings. Carer sense of coherence and being a spouse were associated with more positive baseline RQ carer assessments. Higher levels of neuropsychiatric symptoms were linked to decline in carers' RQ, whereas social support was associated with more positive RQ trajectories. CONCLUSION: This study provides a valuable insight into the course of RQ. LGM proved useful to explore the factors that influence RQ trajectories and variability within- and between-persons. Our findings emphasise the importance of carer-perceived social support and sense of coherence, and of reducing neuropsychiatric symptoms, in maintaining a good RQ.

Associations between unmet needs for daytime activities and company and scores on the Neuropsychiatric Inventory-Questionnaire in people with dementia: a longitudinal study.

OBJECTIVES: To examine prospectively the association between unmet needs for daytime activities and company and behavioural and psychological symptoms of dementia. METHODS: We included 451 people with mild or moderate dementia, from eight European countries, who were assessed three times over 12 months. Unmet needs were measured with the Camberwell Assessment of Need for the Elderly. Three sub-syndromes of the Neuropsychiatric Inventory-Questionnaire were regressed, one-by-one, against unmet needs for daytime activities and company, adjusting for demographic and clinical-functional covariates. RESULTS: Unmet needs for daytime activities were associated with more affective symptoms at baseline, six and twelve months, mean 0.74 (p < 0.001), 0.76 (p < 0.001) and 0.78 (p = 0.001) points higher score respectively, and with more psychotic symptoms at baseline (mean 0.39 points, p = 0.007) and at six months follow-up (mean 0.31 points, p = 0.006). Unmet needs for company were associated with more affective symptoms at baseline, six and twelve months, mean 0.44 (p = 0.033), 0.67 (p < 0.001) and 0.91 (p < 0.001) points higher score respectively, and with more psychotic symptoms at baseline (mean 0.40 points, p = 0.005) and at six months (mean 0.35 points, p = 0.002) follow-up. CONCLUSION: Interventions to reduce unmet needs for daytime activities and company could reduce affective and psychotic symptoms in people with dementia.

Cognitive Tele-Enhancement in Healthy Older Adults and Subjects With Subjective Memory Complaints: A Review.

Background: In recent years, emphasis has been placed on cognitive enhancement to stimulate cognitive abilities and prevent functional decline. Considering that traditional face-to-face interventions can be very expensive and are not accessible to all individuals, the need to transfer care from the clinic to the patient's home is evident. In this regard, cognitive tele-enhancement interventions have received increased attention. Aim: The aim of this review was to provide an overview of protocols that apply remotely controlled cognitive training with individualized feedback on performance by the therapist in healthy older adults or participants with subjective memory complaints. Methods: Out of 35 articles assessed for eligibility, eight studies were identified. Of the selected studies, five included cognitively healthy older adults, while three included participants with subjective memory complaints. Results: Most of the reviewed studies showed beneficial effects of cognitive tele-enhancement interventions, reporting improvements in memory, sustained attention, working memory, executive functions, and language abilities. Moreover, reductions in anxiety and depression symptomatology levels, as well as in subjective memory difficulties, were described in some of the studies. Conclusions: Cognitive tele-enhancement treatment could be a good alternative to face-to-face intervention. This literature review highlights the importance of applying preventive cognitive interventions to subjects with initial subjective memory complaints. Remote modalities seem to facilitate the application of such interventions.

Challenges in the management of chronic wound infections.

OBJECTIVES: Chronic wound infections may delay the healing process and are responsible for a significant burden on healthcare systems. Since inappropriate management may commonly occur in the care of these patients, this review aims to provide a practical guide underlining actions to avoid in the management of chronic wound infections. METHODS: We performed a systematic review of the literature available in PubMed in the last 10 years, identifying studies regarding the management of patients with chronic wound infections. A panel of experts discussed the potential malpractices in this area. A list of 'Don'ts', including the main actions to be avoided, was drawn up using the 'Choosing Wisely' methodology. RESULTS: In this review, we proposed a list of actions to avoid for optimal management of patients with chronic wound infections. Adequate wound bed preparation and wound antisepsis should be combined, as the absence of one of them leads to delayed healing and a higher risk of wound complications. Moreover, avoiding inappropriate use of systemic antibiotics is an important point because of the risk of selection of multidrug-resistant organisms as well as antibiotic-related adverse events. CONCLUSION: A multidisciplinary team of experts in different fields (surgeon, infectious disease expert, microbiologist, pharmacologist, geriatrician) is required for the optimal management of chronic wound infections. Implementation of this approach may be useful to improve the management of patients with chronic wound infections.

Obtaining EQ-5D-5L utilities from the disease specific quality of life Alzheimer's disease scale: development and results from a mapping study.

PURPOSE: The Quality of Life Alzheimer's Disease Scale (QoL-AD) is commonly used to assess disease specific health-related quality of life (HRQoL) as rated by patients and their carers. For cost-effectiveness analyses, utilities based on the EQ-5D are often required. We report a new mapping algorithm to obtain EQ-5D indices when only QoL-AD data are available. METHODS: Different statistical models to estimate utility directly, or responses to individual EQ-5D questions (response mapping) from QoL-AD, were trialled for patient-rated and proxy-rated questionnaires. Model performance was assessed by root mean square error and mean absolute error. RESULTS: The response model using multinomial regression including age and sex, performed best in both the estimation dataset and an independent dataset. CONCLUSIONS: The recommended mapping algorithm allows researchers for the first time to estimate EQ-5D values from QoL-AD data, enabling cost-utility analyses using datasets where the QoL-AD but no utility measures were collected.

Development of best practice recommendations to enhance access to and use of formal community care services for people with dementia in Europe: a Delphi process conducted by the Actifcare project.

OBJECTIVES: Home-dwelling people with dementia and their informal carers experience barriers impeding access to community care services. This study is a part of the Actifcare project where eight countries participated. The aim was to achieve consensus on best practice recommendations for enhancing access to and use of formal community care services. METHOD: A Delphi consensus process was conducted. A total of 48 professional experts, 14 people with dementia and 20 informal carers rated the importance of 72 statements on a 7-point Likert scale. Consensus was based on the median and level of dispersion. RESULTS: Sixty-two statements reached consensus, resulting in three categories of recommendations. An appointed contact person was central in Recommendations to enhance access. Coordination and flexibility in setting and type of services were among the Recommendations to enhance use. Training of health care personnel and person-centred care were central Recommendations that can facilitate access or use indirectly. CONCLUSION: The Actifcare Best Practice Recommendations suggest practical measures that can be taken by decision makers to enhance access and use of community care services, and thereby enhance quality of care and quality of life for home dwelling people with dementia and their informal carers.

A validation study of the CarerQol instrument in informal caregivers of people with dementia from eight European countries.

PURPOSE: Informal care constitutes an important part of the total care for people with dementia. Therefore, the impact of the syndrome on their caregivers as well as that of health and social care services for people with dementia should be considered. This study investigated the convergent and clinical validity of the CarerQol instrument, which measures and values the impact of providing informal care, in a multi-country sample of caregivers for people with dementia. METHODS: Cross-sectional data from a sample of 451 respondents in eight European countries, collected by the Actifcare project, were evaluated. Convergent validity was analysed with Spearman's correlation coefficients and multivariate correlations between the CarerQol-7D utility score and dimension scores, and other similar quality of life measures such as CarerQol-VAS, ICECAP-O, and EQ-5D. Clinical validity was evaluated by bivariate and multivariate analyses of the degree to which the CarerQol instrument can differentiate between characteristics of caregivers, care receivers and caregiving situation. Country dummies were added to test CarerQol score differences between countries. RESULTS: The mean CarerQol utility score was 77.6 and varied across countries from 74.3 (Italy) to 82.3 (Norway). The scores showed moderate to strong positive correlations with the CarerQol-VAS, ICECAP-O, and EQ-5D health problems score of the caregiver. Multivariate regression analysis showed that various characteristics of the caregiver, care receiver and caregiving situation were associated with caregiver outcomes, but there was no evidence of a country-level effect. CONCLUSION: This study demonstrates the convergent and clinical validity of the CarerQol instrument to evaluate the impact of providing informal care for people with dementia.

Genetic counselling and testing for inherited dementia: single-centre evaluation of the consensus Italian DIAfN protocol.

BACKGROUND: A consensus protocol for genetic counselling and testing of familial dementia, the Italian Dominantly Inherited Alzheimer's and Frontotemporal Network (IT-DIAfN) protocol, has been developed in Italy by a network of expert dementia centres. The aim of this study is to evaluate feasibility and acceptability of the genetic counselling and testing process, as undertaken according to the IT-DIAfN protocol in one of the IT-DIAfN dementia research centres. METHODS: The protocol was tested by a multidisciplinary team at the IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy, on affected individuals with suspected inherited forms of Alzheimer's disease (AD) or frontotemporal dementia (FTD), and to healthy at-risk relatives. The genetic counselling and testing process consisted of (i) pre-test consultation and psychological assessment (ii) genetic testing, (iii) genetic test result disclosure and (iv) follow-up consultation and psychological assessment. RESULTS: Twenty affected individuals from 17 families fulfilled the family history criteria of the IT-DIAfN protocol for suspected inherited dementia (17 for AD, 2 for FTD, 1 for inclusion body myopathy with Paget disease of bone and frontotemporal dementia) and were included in the protocol. Nineteen out of 20 affected individuals received the genetic test result (one left after the pre-test consultation being not ready to cope with an unfavourable outcome). A pathogenic mutation was found in 6 affected individuals (1 in PSEN1, 2 in PSEN2, 1 in GRN, 1 in MAPT, 1 in VCP). Eleven healthy at-risk relatives asked to undergo predictive testing and were included in the protocol. Three completed the protocol, including follow-up; one did not ask for the genetic test result after genetic testing; and eight withdrew before the genetic testing, mainly due to an increased awareness about the possible consequences of an unfavourable test result. To date, no catastrophic reactions were reported at the follow-up. CONCLUSIONS: Our case series shows that a structured genetic counselling and testing protocol for inherited dementia can be implemented in both affected individuals and at-risk relatives in a research setting. The procedure was shown to be safe in terms of occurrence of catastrophic events. A formal validation in larger cohorts is needed.

Older People Living in Long-Term Care Facilities and Mortality Rates During the COVID-19 Pandemic in Italy: Preliminary Epidemiological Data and Lessons to Learn.

Background: Long-Term Care Facilities (LTCF) in Italy have been particularly affected by the COVID-19 pandemic, especially in terms of mortality rates of older residents. However, it is still unclear the actual extent of this situation. The aim of this manuscript is to assess the extent of mortality rates of older adults in LTCF during the pandemic across different regions of Italy, compared to the previous years and to older general population not resident in LTCF. Methods: We extracted and analyzed data collected by three Italian institutions (i.e., Italian Statistician Institute ISTAT, Italian N.I.H, Milan Health Unit) about the number of deaths among older people living in the community and among LTCF residents during the pandemic and the previous years. We also compared the observed mortality rate among LTCF residents in each Italian Region with the corresponding expected number of deaths of the general older adult population to obtain an observed/expected ratio (O/E ratio). Results: During the pandemic, about 8.5% (N = 6,797) of Italian older adults residents in LTCF died. Findings resulting from the O/E ratio suggest that LTCF residents (in particular in the Lombardy Region) show higher mortality rates when compared to expected values of mortality rates among the older general population living in the community. Furthermore, we found that the risk of death among LTCF residents increased about 4 times during the pandemic when compared to the previous years. Conclusions: Mortality rates in LTCF were high during the pandemic, especially in Lombardy. Possible causes of higher mortality rates in LTCF and suggestions for specific targeted interventions are discussed.

Behavioral and Psychological Symptoms of Dementia (BPSD): Clinical Characterization and Genetic Correlates in an Italian Alzheimer's Disease Cohort.

BACKGROUND: The occurrence of Behavioral and Psychological Symptoms of Dementia (BPSD) in Alzheimer's Disease (AD) patients hampers the clinical management and exacerbates the burden for caregivers. The definition of the clinical distribution of BPSD symptoms, and the extent to which symptoms are genetically determined, are still open to debate. Moreover, genetic factors that underline BPSD symptoms still need to be identified. PURPOSE: To characterize our Italian AD cohort according to specific BPSD symptoms as well as to endophenotypes. To evaluate the associations between the considered BPSD traits and COMT, MTHFR, and APOE genetic variants. METHODS: AD patients (n = 362) underwent neuropsychological examination and genotyping. BPSD were assessed with the Neuropsychiatric Inventory scale. RESULTS: APOE and MTHFR variants were significantly associated with specific single BPSD symptoms. Furthermore, "Psychosis" and "Hyperactivity" resulted in the most severe endophenotypes, with APOE and MTHFR implicated as both single risk factors and "genexgene" interactions. CONCLUSIONS: We strongly suggest the combined use of both BPSD single symptoms/endophenotypes and the "genexgene" interactions as valid strategies for expanding the knowledge about the BPSD aetiopathogenetic mechanisms.

Profiles of Met and Unmet Needs in People with Dementia According to Caregivers' Perspective: Results from a European Multicenter Study.

OBJECTIVES: This exploratory study aimed at investigating profiles of care needs in people with mild to moderate dementia and examined variables associated with these profiles. DESIGN: A longitudinal international cohort study. SETTING AND PARTICIPANTS: The baseline data of 447 community-dwelling dyads of people with dementia and their caregivers from the Access to Timely Formal Care (Actifcare) Study were included for analysis. METHODS: A latent class analysis was applied to identify profiles of needs, measured with the Camberwell Assessment of Need for the Elderly as rated by the caregiver. We examined sociodemographic (eg, relative stress scale) and clinical characteristics (eg, neuropsychiatric inventory) associated with these profiles. RESULTS: Four distinct need profiles were identified through latent class analysis. These comprised a "no need" profile (41% of the sample), a "met psychological needs" profile (25%), a "met social needs" profile (19%), and an "unmet social needs" profile (15%). A larger impact of caregiving on the caregiver's life as indicated by a higher relative stress scale score was associated with the "unmet social needs" profile. CONCLUSIONS AND IMPLICATIONS: In this large European sample, there was a subgroup of persons with dementia with high "unmet social needs" whose caregivers simultaneously perceived high stress in their caregiving tasks. Identification of these profiles may help provision of appropriate support for these people.