Medication exposure of the dyad patient-caregiver in Alzheimer's disease and related dementias: a cross-sectional study.

BACKGROUND: Patients with Alzheimer's disease and related dementias and their caregivers can be defined as people with higher risk of developing medication-related problems due to aging and polypharmacy. AIM: To assess the medication exposure of patient with Alzheimer's disease and related dementias and their caregivers. METHOD: Ancillary cross-sectional study based on baseline medication data of the PHARMAID RCT. The PHARMAID study was a multi-center RCT assessing an integrated pharmaceutical care at a psychosocial program. Older outpatients with Alzheimer's disease and related dementias and their older caregivers were eligible for inclusion. Baseline medication data were used to assess the medication exposure, illustrated by the number of medications, the prevalence of potentially inappropriate medications (PIMs) using the EU(7)-PIM list and the Medication Regimen Complexity Index (MRCI). RESULTS: Seventy-three dyads were included in this ancillary study. The mean numbers (SD) of medications used by patients was 6.8 (2.6) and by caregivers was 4.7 (3.7). Overall, 60.3% of patients used at least one PIM and 47.9% of caregivers. Regarding the medication regimen complexity, the mean MRCI was 16.3(8.1) for patients and 11.3(10.5) for caregivers. CONCLUSION: The results of this study confirm the relevance of carrying out medication review with patients, but also with their caregivers who can be considered as hidden patients.

Impact of pharmaceutical care integrated at a psychosocial intervention to reduce caregiver's burden in Alzheimer's disease or related dementias: Negative results at 18 months and difficulties to conduct PHARMAID RCT.

Background: Psychosocial interventions for caregivers of patients with Alzheimer disease and relative dementias (ADRD) reported a caregiver burden improvement. Multicomponent intervention integrating pharmaceutical care has not yet been evaluated while ADRD patients and their caregivers are exposed to high risk of drug-related problems. The PHARMAID study aimed to assess the impact of personalized pharmaceutical care integrated to a psychosocial program on the burden of ADRD caregivers at 18 months. Methods: The PHARMAID RCT was conducted between September 2016 and June 2020 [ClinicalTrials.gov: NCT02802371]. PHARMAID study planned to enroll 240 dyads, i.e. ADRD patients and caregivers, whose inclusion criteria were: outpatient with mild or major neurocognitive disorders due to ADRD, living at home, receiving support from a family caregiver. Three parallel groups compared a control group with two interventional groups: psychosocial intervention and integrated pharmaceutical care at a psychosocial intervention. The main outcome was the caregiver burden assessed by the Zarit Burden Index (ZBI, score range 0-88) at 18 months. Results: Overall, 77 dyads were included (32% of the expected sample size). At 18 months, the mean ZBI scores were 36.7 ± 16.8 in the control group, 30.3 ± 16.3 for the group with psychosocial intervention, and 28.8 ± 14.1 in group with integrated pharmaceutical care at psychosocial intervention. No significant difference was demonstrated between the three groups (p = 0.326). Conclusions: The findings suggest that PHARMAID program had no significant impact on caregiver burden at 18 months. Several limitations have been highlighted and discussed by the authors in order to formulate recommendations for further research.

Serum neutralization of SARS coronavirus 2 Omicron sublineages BA.1 and BA.2 and cellular immune responses 3 months after booster vaccination.

OBJECTIVES: We investigated serum neutralizing activity against BA.1 and BA.2 Omicron sublineages and T cell response before and 3 months after administration of the booster vaccine in healthcare workers (HCWs). METHODS: HCWs aged 18-65 years who were vaccinated and received booster doses of the BNT162b2 vaccine were included. Anti-SARS coronavirus 2 IgG levels and cellular response (through interferon γ ELISpot assay) were evaluated in all participants, and neutralizing antibodies against Delta, BA.1, and BA.2 were evaluated in participants with at least one follow-up visit 1 or 3 months after the administration of the booster dose. RESULTS: Among 118 HCWs who received the booster dose, 102 and 84 participants attended the 1-month and 3-month visits, respectively. Before the booster vaccine dose, a low serum neutralizing activity against Delta, BA.1, and BA.2 was detectable in only 39/102 (38.2%), 8/102 (7.8%), and 12/102 (11.8%) participants, respectively. At 3 months, neutralizing antibodies against Delta, BA.1, and BA.2 were detected in 84/84 (100%), 79/84 (94%), and 77/84 (92%) participants, respectively. Geometric mean titres of neutralizing antibodies against BA.1 and BA.2 were 2.2-fold and 2.8-fold reduced compared with those for Delta. From 1 to 3 months after the administration of the booster dose, participants with a recent history of SARS coronavirus 2 infection (n = 21/84) had persistent levels of S1 reactive specific T cells and neutralizing antibodies against Delta and BA.2 and 2.2-fold increase in neutralizing antibodies against BA.1 (p 0.014). Conversely, neutralizing antibody titres against Delta (2.5-fold decrease, p < 0.0001), BA.1 (1.5-fold, p 0.02), and BA.2 (2-fold, p < 0.0001) declined from 1 to 3 months after the administration of the booster dose in individuals without any recent infection. DISCUSSION: The booster vaccine dose provided significant and similar response against BA.1 and BA.2 Omicron sublineages; however, the immune response declined in the absence of recent infection.

The effect of the severity of neurocognitive disorders on emotional and motor responses to music.

The successful design of musical interventions for dementia patients requires knowledge of how rhythmic abilities change with disease severity. In this study, we tested the impact of the severity of the neurocognitive disorders (NCD) on the socioemotional and motor responses to music in three groups of patients with Major NCD, Mild NCD, or No NCD. Patients were asked to tap to a metronomic or musical rhythm while facing a live musician or through a video. We recorded their emotional facial reactions and their sensorimotor synchronization (SMS) abilities. Patients with No NCD or Mild NCD expressed positive socioemotional reactions to music, but patients with Major NCD did not, indicating a decrease in the positive emotional impact of music at this stage of the disease. SMS to a metronome was less regular and less precise in patients with a Major NCD than in patients with No NCD or Mild NCD, which was not the case when tapping with music, particularly in the presence of a live musician, suggesting the relevance of live performance for patients with Major NCD. These findings suggest that the socioemotional and motor reactions to music are negatively affected by the progression of the NCD.

Hypnosis Intervention for Couples Confronted with Alzheimer's Disease: Promising Results of a First Exploratory Study.

BACKGROUND: Dementia has a negative impact on the quality of life of the person with dementia and their spouse caregivers, as well as on the couple's relationship, which can lead to high levels of distress for both partners. Hypnosis has been shown to be effective in managing distress and increasing the quality of the relationship. OBJECTIVE: The aim was to develop a standardized hypnosis intervention for couples confronted with Alzheimer's disease and evaluate its feasibility, acceptability, and helpfulness in managing the distress of both partners and increasing the quality of the relationship. METHODS: In a single-arm study, sixteen couples received the 8-week intervention. Qualitative and quantitative assessments were conducted pre- and post-intervention as well as three months after. RESULTS: 88.9% of couples (n = 16) of the final sample (n = 18) completed the intervention. Despite the negative representations of hypnosis, several factors led couples to accept to participate in this study: positive expectations, professional endorsement, medical application, non-drug approach, home-based, free, flexible, and couple-based intervention. The results showed a significant decrease in distress for both partners. These effects were maintained three months after the intervention. Couples felt more relaxed, had fewer negative emotions, accepted difficulties more easily, were more patient, and reported better communication and more affection in the relationship. CONCLUSION: Overall, this pilot study shows the feasibility and acceptability of hypnosis with couples confronted with Alzheimer's disease. Although measures of the preliminary pre- and post-intervention effects are encouraging, confirmatory testing with a randomized controlled trial is needed.

Immunogenicity of BNT162b2 vaccine booster against SARS-CoV-2 Delta and Omicron variants in nursing home residents: A prospective observational study in older adults aged from 68 to 98 years.

Background: The present study aimed to evaluate the persistent immunogenicity offered by a third dose of BNT162b2 against Delta and Omicron variants, in nursing home (NH) residents. Methods: In this monocenter prospective observational study, anti-spike IgG levels, S1 domain reactive T cell counts, serum neutralizing antibody titers against Delta and Omicron variants were compared before and up to three months after the BNT162b2 booster dose, in NH residents without COVID-19 (COVID-19 naive) or with COVID-19 prior to initial vaccination (COVID-19 recovered). Findings: 106 NH residents (median [interquartile range] age: 86·5 [81;91] years) were included. The booster dose induced a high increase of anti-spike antibody levels in all subjects (p < 0.0001) and a mild transient increase of specific T cells. Before the booster dose, Delta neutralization was detected in 19% (n = 8/43) and 88% (n = 37/42) of COVID-19 naive and COVID-19 recovered subjects, respectively. Three months after the booster dose, all NH residents developed and maintained a higher Delta neutralization (p < 0·0001). Before the booster dose, Omicron neutralization was detected in 5% (n = 2/43) and 55% (n = 23/42) of COVID-19 naive and COVID-19 recovered subjects, respectively, and three months after, in 84% and 95%, respectively. Neutralizing titers to Omicron were lower than to Delta in both groups with a 35-fold reduction compared to Delta. Interpretation: The booster dose restores high neutralization titers against Delta in all NH residents, and at a lower level against Omicron in a large majority of participants. Future studies are warranted to assess if repeated BNT162b2 booster doses or new specific vaccines might be considered for protecting such fragile patients against Omicron and/or future SARS-CoV-2 variants. Funding: French government through the Programme Investissement d'Avenir (I-SITE ULNE/ANR-16-IDEX-0004 ULNE) and the Label of COVID-19 National Research Priority (National Steering Committee on Therapeutic Trials and Other COVID-19 Research, CAPNET).

Sensorimotor Synchronization in Healthy Aging and Neurocognitive Disorders.

Sensorimotor synchronization (SMS), the coordination of physical actions in time with a rhythmic sequence, is a skill that is necessary not only for keeping the beat when making music, but in a wide variety of interpersonal contexts. Being able to attend to temporal regularities in the environment is a prerequisite for event prediction, which lies at the heart of many cognitive and social operations. It is therefore of value to assess and potentially stimulate SMS abilities, particularly in aging and neurocognitive disorders (NCDs), to understand intra-individual communication in the later stages of life, and to devise effective music-based interventions. While a bulk of research exists about SMS and movement-based interventions in Parkinson's disease, a lot less is known about other types of neurodegenerative disorders, such as Alzheimer's disease, vascular dementia, or frontotemporal dementia. In this review, we outline the brain and cognitive mechanisms involved in SMS with auditory stimuli, and how they might be subject to change in healthy and pathological aging. Globally, SMS with isochronous sounds is a relatively well-preserved skill in old adulthood and in patients with NCDs. At the same time, natural tapping speed decreases with age. Furthermore, especially when synchronizing to sequences at slow tempi, regularity and precision might be lower in older adults, and even more so in people with NCDs, presumably due to the fact that this process relies on attention and working memory resources that depend on the prefrontal cortex and parietal areas. Finally, we point out that the effect of the severity and etiology of NCDs on sensorimotor abilities is still unclear: More research is needed with moderate and severe NCD, comparing different etiologies, and using complex auditory signals, such as music.

Impaired Functional T-Cell Response to SARS-CoV-2 After Two Doses of BNT162b2 mRNA Vaccine in Older People.

Long-term care facility (LTCF) older residents display physiological alterations of cellular and humoral immunity that affect vaccine responses. Preliminary reports suggested a low early postvaccination antibody response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The aim of this study was to focus on the specific T-cell response. We quantified S1-specific IgG, neutralizing antibody titers, total specific IFNγ-secreting T cells by ELISpot, and functionality of CD4+- and CD8+-specific T cells by flow cytometry, after two doses of the BNT162b2 vaccine in younger and older people, with and without previous COVID-19 infection (hereafter referred to as COVID-19-recovered and COVID-19-naive subjects, respectively). Frailty, nutritional, and immunosenescence parameters were collected at baseline in COVID-19-naive older people. We analyzed the immune response in 129 young adults (median age 44.0 years) and 105 older residents living in a LCTF (median age 86.5 years), 3 months after the first injection. Humoral and cellular memory responses were dramatically impaired in the COVID-19-naive older (n = 54) compared with the COVID-19-naive younger adults (n = 121). Notably, older participants' neutralizing antibodies were 10 times lower than the younger's antibody titers (p < 0.0001) and LCTF residents also had an impaired functional T-cell response: the frequencies of IFNγ+ and IFNγ+IL-2+TNFα+ cells among specific CD4+ T cells, and the frequency of specific CD8+ T cells were lower in COVID-19-naive older participants than in COVID-19-naive young adults (p < 0.0001 and p = 0.0018, respectively). However, COVID-19-recovered older participants (n = 51) had greater antibody and T-cell responses, including IFNγ+ and IFNγ+IL-2+TNFα+-specific CD4+ T cells (p < 0.0001), as well as TNFα+-specific CD8+ T cells (p < 0.001), than COVID-19-naive older adults. We also observed that "inflammageing" and particularly high plasma levels of TNFα was associated to poor antibody response in the older participants. In conclusion, our results show that the COVID-19-naive older people had low counts and impaired specific CD4+ and CD8+ T cells, in addition to impaired antibody response, and that specific studies are warranted to assess the efficiency of SARS-CoV-2 mRNA-based vaccines, as in other immunocompromised subjects. Our study also shows that, despite their physiological alterations of immunity, vaccination is highly efficient in boosting the prior natural memory response in COVID-19-recovered older people.

Socio-emotional and motor engagement during musical activities in older adults with major neurocognitive impairment.

Although music therapy may engender clinical benefits in patients with neurodegenerative disease, the impacts of social and musical factors of such activities on socio-emotional and motor engagements are poorly understood. To address this issue, non-verbal behaviors of 97 patients with or without major cognitive impairment (CI) were assessed when listening to music or a metronome in front of a musician who was present physically (live) or virtually (video). Socio-emotional engagement was quantified as emotional facial expression production and gaze direction. Motor engagement was quantified as overall body motion and the production of rhythmic movements. In both groups, positive facial expressions were more frequent and rhythmic motor activities lasted longer with music than with a metronome, and during a live performance rather than a video performance. Relative to patients without CI, patients with CI moved less with music, expressed fewer emotions, and spent less time looking at the musician in the video condition and in the metronome condition. The relative reductions in motor and socio-emotional engagements in patients with CI might be markers of disease progression. However, the presence of a live partner induces older adults to engage emotionally and physically in musical activities emphasizing the relevance of using live performance as motivational levers during music therapy.

Institutionalization of older French adults with dementia: Role of the informal carer's degree of kinship.

BACKGROUND: The institutionalization of a patient with Alzheimer's disease or other dementia (ADOD) is the last resort for the latter's family and/or caregivers. We hypothesized that the degree of kinship between the patient and his/her caregiver would influence the likelihood of institutionalization. OBJECTIVE: To assess the association between institutionalization of patients with ADOD and the degree of kinship with the family caregiver. METHODS: A cross-sectional study of patients with ADOD aged 75 or over attending a memory center in France for the first time between 2011 and 2014, as recorded in the French National Alzheimer Database. Multivariable logistic regression was used to assess factors associated with institutionalization after adjustment for age, sex, the Mini-Mental State Examination score, educational level, and type of dementia. RESULTS: A total of 52,874 patients were included. The primary caregiver was most often a child (54.8%) or the spouse (36.7%). Compared with the "spouse" reference category, all the other caregiver categories were associated with a significantly greater likelihood of institutionalization; the odds ratio [95% confidence interval] was 4.68 [3.67-5.92] when the carer was a grandchild, 5.48 [4.93-6.09] for a child, 4.93 [4.11-5.91] for a daughter-/son-in-law, 8.76 [7.15-10.70] for a sibling, and 8.93 [7.48-10.65] for a niece/nephew. CONCLUSION: The likelihood of institutionalization of older patients with ADOD varied with the degree of kinship. Compared with the "spouse" reference category, the likelihood was higher for all other types of caregivers but was especially high when the caregiver was not a direct descendant of the patient.

Does a Live Performance Impact Synchronization to Musical Rhythm in Cognitively Impaired Elderly?

BACKGROUND: Music-based interventions appear to be efficient approaches to improve emotional, social, and cognitive functioning of patients with neurodegenerative diseases. OBJECTIVE: Because benefits seem to increase with patient's motor involvement, we studied sensorimotor synchronization (SMS) abilities of patients with cognitive impairments (Alzheimer's disease, vascular and mixed dementia) and of patients with no evidence of cognitive impairments. More specifically, we compared the impact of a live performance by a musician to a video recording on SMS. METHODS: SMS to a metronomic or a musical stimulus was assessed while patients watched a live musician or his pre-recorded video. RESULTS: SMS to a metronome was better than to music but this effect was modulated by the social context. While SMS to a metronome was better when facing a video than a live performance, there was no impact of social context on SMS to music. No group differences of SMS were found. CONCLUSION: The decrease in SMS to a metronome in a live performance may be due to social pressure. Such a pressure might be removed in pleasant social activities, like moving with music in a group, explaining the lack of effect on SMS to music. We found no performance differences in groups, suggesting relatively spared SMS in cognitively impaired patients. By showing that it is possible to encourage patients to synchronize with others, even when facing a video, our results indicate that SMS can be used as a relevant predictor in clinical trials and open up promising therapeutic options for isolated patients.

Twenty-year trends in patient referrals throughout the creation and development of a regional memory clinic network.

INTRODUCTION: Memory clinics (MCs) are the main model for dementia diagnosis and care. Following the development of a MC network in Northern France, our objectives were to assess its impact on patient characteristics over 20 years. METHODS: The characteristics of new consultants were studied from 1997 to 2016. RESULTS: New consultants increased from 774 per year in 1997 to 26258 per year in 2016, as the number of MCs increased from 12 to 29. Over time, patients were progressively older and less educated, and more were living alone. A greater proportion of patients were referred by specialists. Referral delay and home-to-MC distance kept decreasing. The oldest patients were referred at a progressively less-severe stage. The proportion of young patients kept increasing in the tertiary referral center. DISCUSSIONS: The development of a region-wide MC network led to increased referral of vulnerable patients and differentiation of the tertiary referral center over time.

[Geriatric units at the beginning of the 2020 COVID-19 epidemic in France]. / Les unités de gériatrie au début de l'épidémie du Covid-19 de 2020 en France.

The COVID-19 epidemic that started in November in China became a national epidemic from March 16, 2020 with the declaration of population containment in order to reduce the spread of the virus in France. From March 17 to March 27, 2020, the monitoring unit of the French society of geriatrics and gerontology decided to conduct a survey to analyze the implementation of the mobilization of geriatric units, given that this epidemic had shown that it resulted in excess mortality mainly among the elderly. The survey was able to bring together the response of 34 services, nine of which were located in a high epidemic cluster zone. Dedicated acute geriatric units for patients infected with COVID-19 were present in eight facilities, only outside the cluster zones. Nine geriatric follow-up and rehabilitation services were dedicated, an additional telemedicine activity concerned 35% of the facilities, and family listening and tablet communication facilities concerned 36% of the facilities. This survey is a snapshot of an initial moment in the epidemic. It provides an opportunity to describe the context in which this epidemic occurred in terms of geriatric policy, and to assess the responsiveness and inventiveness of these services in meeting the needs of the elderly.

[Alcohol consumption patterns in older people living in nursing homes]. / La consommation d'alcool en établissement d'hébergement pour personnes âgées dépendantes est excessive.

BACKGROUND: Although frail elderly people are particularly vulnerable to the adverse effects of alcohol, very little work on alcohol consumption patterns in older people living in nursing homes has been undertaken. OBJECTIVE: To determine alcohol consumption patterns among the residents of 8 nursing homes of the Nord Pas-de-Calais in France, and the characteristics associated with heavy drinking (≥ 3 glasses of wine or equivalent/day). METHODS: All residents were invited to participate in the study on condition that they satisfied the inclusion criteria (age ≥ 60 years, Mini Mental State of Folstein (MMSE) > 15, agreement) and the exclusion criteria (no oral communication, end of life). Two questionnaires were used, one for the residents and the other for the personnel nursing. RESULTS: Three hundred and sixty-eight residents [242 females (65.8%) and 126 males (34.2%); mean age, 80.5 ± 8.9 years] participated in the study. Among them, 98 (26.6%) reported no consumption of alcohol and 21 (5.7%) reported occasional consumption. The 249 (67.7%) others reported every-day consumption, principally in the restaurant at the time of the meals. Sixty-seven (18.2%), were heavy drinkers with an early-onset alcoholism for two out of three. Compared with the other residents participating in the study, the at-risk alcohol drinkers were younger and more likely to be a man. CONCLUSION: The study confirms that the prevalence of chronic at risk consumption is high in nursing homes. More efforts are needed to identify and improve management of alcohol disorders in this particular setting.

[Lung diseases in the elderly. Assessment of guidelines for the probabilistic prescription of antibiotics in a department of geriatric care]. / Pneumopathies du sujet âgé. Evaluation d'un guide de prescription d'antibiothérapie probabiliste dans un service de médecine gériatrique.

OBJECTIVE: We developed a prescribing guideline containing recommendations for the initial empirical antibiotic therapy in community or nosocomial pneumonia. The aim of the present study was to examine the impact of this measure. METHOD: The prescribing guideline was implemented in May 1999. We retrospectively reviewed the charts of all patients>65 years with community-, or nursing home- or hospital-acquired pneumonia hospitalised in our department of acute geriatric care between May 1999 and November 2000. The criteria assessed were: consistence with the guideline, clinical effectiveness within 72 hours, adequation with the isolated germs and intra-hospital mortality. RESULTS: Data were collected on 112 patients (63 women et 49 men; mean age=80 +/- 8 Years). The pneumonia was community-acquired in 52 cases (46%), nursing home acquired in 25 cases (22%) and hospital-acquired in 35 cases (31%). Antibiotic prescription was consistent with the guideline in 64 cases (57%). When the antibiotic therapy was consistent, the patients were more likely to improve within 72 hours (45/64 versus 23/48; p=0.01). Despite a tendency, the number of antimicrobial treatments adapted to the isolated microorganisms was not significantly higher in the consistent group (22/36 adapted treatments versus 10/20). The intra-hospital mortality (25%) was similar in the two groups consistent and not consistent with the guideline. SARM was the most frequent multiresistant bacteria that was isolated. CONCLUSION: The use of a prescribing guideline might improve the efficiency of empirical probabilistic antibiotic therapies. The impact of the guideline use on overall antibiotic costs and microbiological flora remains to be determined.