Limited awareness of hallucinations in patients with Alzheimer's disease.

INTRODUCTION: We investigated the degree of cognitive insight in patients with Alzheimer's Disease (AD) regarding their hallucinations, aiming to elucidate the subjective experiences and perceptions associated with this phenomenon. METHODS: Using a cross-sectional design, we invited both AD patients (n = 31) and their informants to evaluate the occurrence of hallucinations. Degree of cognitive insight was based upon the discrepancy between the patients' and informants' evaluations. RESULTS: Analysis demonstrated that AD patients rated the occurrence of hallucinations lower than their informants, indicating that patients tended to underestimate the frequency of their hallucinations. The discrepancy between the ratings of patients and informants was negatively correlated with cognitive functioning, suggesting that a greater discrepancy (indicating poorer insight) was associated with lower cognitive functioning in patients. DISCUSSION: Our findings highlight the deficits in insight into hallucinations among AD patients, specifically indicating that AD patients have limited awareness of their own hallucinations. Furthermore, our findings support the idea that deficits in insight into hallucinations are associated with the progression of AD.

The recombined memory: associative inference in Alzheimer's disease.

BACKGROUND: Associative inference refers to an adaptive ability that allows flexible recombination of information acquired during previous experiences to make new connections that they have not directly experienced. This cognitive ability has been widely associated with the hippocampus. AIMS: We investigated associative inference in patients with Alzheimer's disease and control participants. METHODS: The task has two phases. In the training phase, participants learned to encode overlapping pairs of objects (AB + BC). In the test phase, participants were invited to retrieve previously see associations (i.e., AB, BC) as well as novel associations between the previously exposed objects (i.e., AC). In addition, we test the relationship between associative inference and cognitive flexibility. RESULTS: Analysis demonstrated lower associative inference in AD patients than in control participants. Interestingly, performance on the associative inference task was significantly correlated with low performance on a cognitive flexibility task in AD patients. DISCUSSION: Our findings demonstrate a compromise of the ability to flexibly combine new representations from prior memories in AD, which is likely related to the hippocampal dysfunction in AD.

Executive dysfunction and effectiveness of physical program in older adults: which association?

BACKGROUND: Little is known about the association between executive function and the magnitude of improvement from personalised exercise interventions on gait performance among older-old adults. AIM: We examined whether the effectiveness of personalised intervention on gait performance is dependent on the patient's baseline dysexecutive syndrome, as assessed by the Frontal Assessment Battery. METHODS: A total of 175 older community-dwellers (83.57 ± 5.2 years; 70.2% female) were recruited from the day centre for after-care and rehabilitation in the Nantes Ambulatory Centre of the Clinical Gerontology (France), and were followed during a pre-post-intervention, single-arm retrospective design. The intervention consisted of an individual personalised rehabilitation program over a period of 7 weeks, with twice-weekly sessions (45 min each). Gait speed in four conditions (preferred, fast, and under two dual-task conditions), Timed Up and Go test, and handgrip strength test were assessed. RESULTS: Using a pre-post analysis of covariance, a significant increase in dual-task gait speed while counting (+ 0.10 m/s; + 15%) and in dual-fluency gait speed (+ 0.06 m/s; + 10%), and in Timed Up and Go performance (- 2.9 s; + 17.8%) was observed after the rehabilitation program, regardless the baseline executive status. DISCUSSION: An individual personalized intervention is effective to improve mobility performance and the dual-task gait speed in older-old adults. The magnitude of those effects is independent of the patient's baseline characteristics including the executive function status. CONCLUSIONS: Even the most deficient baseline characteristics of patients should not be viewed as clinical barrier for implementing a beneficial individual intervention in high-risk older adults.

Déjà vu and involuntary autobiographical memories as two distinct cases of familiarity in patients with Alzheimer's disease.

The continuum between involuntary autobiographical memories and déjà vu, as proposed by Barzykowski and Moulin, can be better defined by considering research on autobiographical retrieval in patients with Alzheimer's disease. Although autobiographical retrieval in patients with Alzheimer's disease can generally be associated with a sense of familiarity, involuntary retrieval can trigger an autonoetic experience of retrieval in these patients.

High-dose versus standard-dose vitamin D supplementation in older adults with COVID-19 (COVIT-TRIAL): A multicenter, open-label, randomized controlled superiority trial.

BACKGROUND: Vitamin D supplementation has been proposed as a treatment for Coronavirus Disease 2019 (COVID-19) based on experimental data and data from small and uncontrolled observational studies. The COvid19 and VITamin d TRIAL (COVIT-TRIAL) study was conducted to test whether a single oral high dose of cholecalciferol (vitamin D3) administered within 72 hours after the diagnosis of COVID-19 improves, compared to standard-dose cholecalciferol, the 14-day overall survival among at-risk older adults infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). METHODS AND FINDINGS: This multicenter, randomized, controlled, open-label, superiority trial involved collaboration of 9 medical centers in France. Patients admitted to the hospital units or living in nursing homes adjacent to the investigator centers were eligible if they were ≥65 years, had SARS-CoV-2 infection of less than 3 days, and at least 1 COVID-19 worsening risk factor (among age ≥75 years, SpO2 ≤94%, or PaO2/FiO2 ≤300 mm Hg). Main noninclusion criteria were organ failure requiring ICU, SpO2 ≤92% despite 5 L/min oxygen, life expectancy <3 months, vitamin D supplementation >800 IU/day during the preceding month, and contraindications to vitamin D supplements. Eligible and consenting patients were randomly allocated to either a single oral high-dose (400,000 IU) or standard-dose (50,000 IU) cholecalciferol administered under medical supervision within 72 hours after the diagnosis of COVID-19. Participants and local study staff were not masked to the allocated treatment, but the Steering Committee and the Data and Safety Monitoring Board were masked to the randomization group and outcome data during the trial. The primary outcome was 14-day overall mortality. Between April 15 and December 17, 2020, of 1,207 patients who were assessed for eligibility in the COVIT-TRIAL study, 254 met eligibility criteria and formed the intention-to-treat population. The median age was 88 (IQR, 82 to 92) years, and 148 patients (58%) were women. Overall, 8 (6%) of 127 patients allocated to high-dose cholecalciferol, and 14 (11%) of 127 patients allocated to standard-dose cholecalciferol died within 14 days (adjusted hazard ratio = 0.39 [95% confidence interval [CI], 0.16 to 0.99], P = 0.049, after controlling for randomization strata [i.e., age, oxygen requirement, hospitalization, use of antibiotics, anti-infective drugs, and/or corticosteroids] and baseline imbalances in important prognostic factors [i.e., sex, ongoing cancers, profuse diarrhea, and delirium at baseline]). The number needed to treat for one person to benefit (NNTB) was 21 [NNTB 9 to ∞ to number needed to treat for one person to harm (NNTH) 46]. Apparent benefits were also found on 14-day mortality due to COVID-19 (7 (6%) deaths in high-dose group and 14 (11%) deaths in standard-dose group; adjusted hazard ratio = 0.33 [95% CI, 0.12 to 0.86], P = 0.02). The protective effect of the single oral high-dose administration was not sustained at 28 days (19 (15%) deaths in high-dose group and 21 (17%) deaths in standard-dose group; adjusted hazard ratio = 0.70 [95% CI, 0.36 to 1.36], P = 0.29). High-dose cholecalciferol did not result in more frequent adverse effects compared to the standard dose. The open-label design and limited study power are the main limitations of the study. CONCLUSIONS: In this randomized controlled trial (RCT), we observed that the early administration of high-dose versus standard-dose vitamin D3 to at-risk older patients with COVID-19 improved overall mortality at day 14. The effect was no longer observed after 28 days. TRIAL REGISTRATION: ClinicalTrials.gov NCT04344041.

The "Sickness" Memory: Can Patients With Alzheimer Disease Remember the Diagnosis Announcement?

BACKGROUND: Diagnosis of Alzheimer disease (AD) can cause substantial psychological distress in patients. We thus assessed how patients with AD remember the announcement of diagnosis. METHODS: We recruited 47 participants with mild AD (26 women; M age=68.89 y, SD=7.37; M years of formal education=9.74, SD=3.00). We invited the participants to remember the moment when their clinicians announced their diagnosis, within 6 months of the event, as well as a control memory, over the same period. We analyzed memory retrieval regarding specificity, as well as the subjective experience of retrieval (ie, regarding mental time travel, visual imagery, emotion and importance). RESULTS: No significant differences were observed between memory of diagnosis and control memory regarding specificity, mental time travel and visual imagery. However, memory of diagnosis triggered a more intense emotional experience and feeling of importance than control memory. DISCUSSION: Retrieval of the diagnosis announcement can activate a strong emotional and personally important experience in patients with AD. When remembering the diagnosis announcement, patients with AD may re-experience some features of that turning point in which they shift from "person" to "patient."

"Look at the future": Maintained fixation impoverishes future thinking.

We evaluated the relationship between eye movements and future thinking. More specifically, we evaluated whether maintained fixation could influence cognitive characteristics of future thinking. We invited participants to imagine future events in two conditions: while freely exploring a white wall and while fixating a cross on the wall. Results demonstrated fewer and longer fixations, as well as fewer and shorter saccades during maintained fixation condition than in the free gaze condition. Shorter total amplitude of saccades was also observed during the maintained fixation condition than during the free-gaze condition. Regarding the cognitive characteristics of future thinking, fewer spatiotemporal details and less visual imagery, slower retrieval time, and shorter descriptions were observed for future thinking during maintained fixation than during free-gaze condition. These results demonstrate that maintaining fixation results in an effortful construction of future scenarios. We suggest that maintained fixation limits the cognitive resources that are required for future thinking.

Functional decline, long term symptoms and course of frailty at 3-months follow-up in COVID-19 older survivors, a prospective observational cohort study.

BACKGROUND: Aging is one of the most important prognostic factors increasing the risk of clinical severity and mortality of COVID-19 infection. However, among patients over 75 years, little is known about post-acute functional decline. OBJECTIVE: The aim of this study was to identify factors associated with functional decline 3 months after COVID-19 onset, to identify long term COVID-19 symptoms and transitions between frailty statesafter COVID-19 onset in older hospitalized patients. METHODS: This prospective observational study included COVID-19 patients consecutively hospitalized from March to December 2020 in Acute Geriatric Ward in Nantes University Hospital. Functional decline, frailty status and long term symptoms were assessed at 3 month follow up. Functional status was assessed using the Activities of Daily Living simplified scale (ADL). Frailty status was evaluated using Clinical Frailty Scale (CFS). We performed multivariable analyses to identify factors associated with functional decline. RESULTS: Among the 318 patients hospitalized for COVID-19 infection, 198 were alive 3 months after discharge. At 3 months, functional decline occurred in 69 (36%) patients. In multivariable analysis, a significant association was found between functional decline and stroke (OR = 4,57, p = 0,003), history of depressive disorder (OR = 3,05, p = 0,016), complications (OR = 2,24, p = 0,039), length of stay (OR = 1,05, p = 0,025) and age (OR = 1,08, p = 0,028). At 3 months, 75 patients described long-term symptoms (49.0%). Of those with frailty (CFS scores ≥5) at 3-months follow-up, 30% were not frail at baseline. Increasing frailty defined by a worse CFS state between baseline and 3 months occurred in 41 patients (26.8%). CONCLUSIONS: This study provides evidence that both the severity of the COVID-19 infection and preexisting medical conditions correlates with a functional decline at distance of the infection. This encourages practitioners to establish discharge personalized care plan based on a multidimensional geriatric assessment and in parallel on clinical severity evaluation.

"My sympathetic clinician": perception of sympathy by patients with Alzheimer's disease increases when asked to provide autobiographical memories.

BACKGROUND AND AIMS: Autobiographical memory serves to recall past personal experiences and share them with others, promoting social bonding and communication. In this study, we investigated whether encouraging patients with Alzheimer's disease (AD) to share autobiographical memories during formal neuropsychological testing may boost the patient-clinician relationship, and more specifically, the neuropsychologist's level of sympathy as perceived by patients. METHODS: We invited patients with mild AD to perform neuropsychological testing in two conditions. In one condition, we invited patients to retrieve and share two autobiographical memories after testing, while in a control condition, the testing session ended without asking patients to retrieve and share any autobiographical memories. After the two conditions, patients were invited to rate the neuropsychologist's level of sympathy towards them. RESULTS: Analysis demonstrated that patients perceived a higher level of sympathy when their neuropsychologist invited them to retrieve and share past personal experiences. DISCUSSION: By inviting patients with AD to retrieve past personal experiences, clinicians can promote a sense of sharing, create a social bond and, consequently, enhance the therapeutic relationship. In other words, by inviting patients with AD to share autobiographical memories, clinicians can promote a "social glue" with their patients, boosting mutual sympathy and patients' well-being.

"Who will I be?": The future of the self as described by Alzheimer's disease (AD) patients.

We assessed how Alzheimer's disease (AD) patients would imagine their self in the future. AD patients and healthy controls were asked to generate statements beginning with "I-will-be" to describe how they saw themselves or how they wished to be in the future. These statements were analyzed in terms of four self-dimensions, i.e., physical self, social self, psychological self and self-cessation. The latter was investigated to assess how AD patients processed the idea of their own mortality. Findings demonstrated fewer total "I-will-be" statements in AD participants than in controls, suggesting that the construction of future self-concepts becomes weaker in the disease. Our results also demonstrated fewer statements related to the physical-self, the social-self and the psychological-self, and more statements related to self-cessation in AD participants than in controls. These findings suggest that AD patients are highly preoccupied by the idea of death when thinking about the future of their self.

Tau in the gut, does it really matter?

The enteric nervous system plays a critical role in the regulation of gastrointestinal tract functions and is often referred to as the 'second brain' because it shares many features with the central nervous system. These similarities include among others a large panel of neurotransmitters, a large population of glial cells and a susceptibility to neurodegeneration. This close homology between the central and enteric nervous systems suggests that a disease process affecting the central nervous system could also involve its enteric counterpart. This was already documented in Parkinson's disease, the most common synucleinopathy, in which alpha-synuclein deposits are reported in the enteric nervous system in the vast majority of patients. Tau is another key protein involved in neurodegenerative disorders of the brain. Whether changes in tau also occur in the enteric nervous system during gut or brain disorders has just begun to be explored. The scope of the present article is therefore to review existing studies on the expression and phosphorylation pattern of tau in the enteric nervous system under physiological and pathological conditions and to discuss the possible occurrence of 'enteric tauopathies'.

Tau accumulates in Crohn's disease gut.

A sizeable body of evidence has recently emerged to suggest that gastrointestinal (GI) inflammation might be involved in the development of Parkinson's disease (PD). There is now strong epidemiological and genetical evidence linking PD to inflammatory bowel diseases and we recently demonstrated that the neuronal protein alpha-synuclein, which is critically involved in PD pathophysiology, is upregulated in inflamed segments of Crohn's colon. The microtubule associated protein tau is another neuronal protein critically involved in neurodegenerative disorders but, in contrast to alpha-synuclein, no data are available about its expression and phosphorylation patterns in inflammatory bowel diseases. Here, we examined the expression levels of tau isoforms, their phosphorylation profile and truncation in colon biopsy specimens from 16 Crohn's disease (CD) and 6 ulcerative colitis (UC) patients and compared them to samples from 16 controls. Additional experiments were performed in full thickness segments of colon of five CD and five control subjects, in primary cultures of rat enteric neurons and in nuclear factor erythroid 2-related factor (Nrf2) knockout mice. Our results show the upregulation of two main human tau isoforms in the enteric nervous system (ENS) in CD but not in UC. This upregulation was not transcriptionally regulated but instead likely resulted from a decrease in protein clearance via an Nrf2 pathway. Our findings, which provide the first detailed characterization of tau in CD, suggest that the key proteins involved in neurodegenerative disorders such as alpha-synuclein and tau, might also play a role in CD.

The effects of inulin on gut microbial composition: a systematic review of evidence from human studies.

BACKGROUND: Inulin, consisting of repetitive fructosyl units linked by ß(2,1) bonds, is a readily fermentable fiber by intestinal bacteria that generates large quantities of short-chain fatty acids (SCFA). In individuals with constipation, it was reported that inulin ingestion was associated with a significant increase in stool frequency, suggesting a potential impact of inulin on human gut microbiota composition. Progress in high-throughput technologies allow assessment of human-associated microbiomes in terms of diversity and taxonomic or functional composition, and can identify changes in response to a specific supplementation. Hence, to understand the effects of inulin on the human gut microbiome is pivotal to gain insight into their mechanisms of action. METHODS: Here, we conducted a systematic review of human studies in adult individuals showing the effects of inulin on the gut microbiome. We searched in MEDLINE, EMBASE, Web of Science, and Scopus databases for articles in English published in peer-reviewed journals and indexed up until March 2019. We used multiple search terms capturing gut microbiome, gut microflora, intestinal microbiota, intestinal flora, gut microbiota, gut flora, microbial gut community, gut microbial composition, and inulin. RESULTS: Overall, nine original articles reported the effects of inulin on microbiome composition in adult humans, most of them being randomized, double-blind, placebo-controlled trials (n = 7). Studies varied significantly in design (3 studies associated inulin and oligofructose), supplementation protocols (from 5 to 20 gr per day of inulin consumed) and in microbiome assessment methods (16S sequencing, n = 7). The most consistent change was an increase in Bifidobacterium. Other concordant results included an increase in relative abundance of Anaerostipes, Faecalibacterium, and Lactobacillus, and a decrease in relative abundance of Bacteroides after inulin supplementation. CONCLUSIONS: Our systematic review assessed the evidence for the effects of inulin supplementation on the human gut microbiome. However, these in vivo studies did not confirm in vitro experiments as the taxonomic alterations were not associated with increase in short-chain fatty acids levels.

Antibiotics prescription and guidelines adherence in elderly: impact of the comorbidities.

BACKGROUND: Although the interest of antibiotics is well known, antibiotics prescription is associated with side effect, especially in patients with multiples comorbidities. One way to reduce the incidence of side effects is to respect antibiotics prescriptions guidelines. Our objective was to investigated the factors associated with guidelines adherence in elderly patients with multiples comorbidities. METHODS: From October 2015 to December 2016, antibiotics prescription and guidelines adherence were analyzed in two post-acute care and rehabilitation services of a 2600-bed, university-affiliated center. RESULTS: One hundred and twenty-eight patients were included, fifty-nine (46%) patients had antibiotics prescription according to guidelines. In Multivariable logistic regression analysis, prescription of 2 antibiotics or more (OR = 0.168, 95% IC = 0.037-0.758, p < 0.05), 85 years of age and more (OR = 0.375, 95% IC = 0.151-0.931, p < 0.05) and the Charlson comorbidity index score (OR = 0.750, 95% IC = 0.572-0.984, p < 0.05) were negatively associated with antibiotics prescriptions according to guidelines. CONCLUSIONS: High comorbidity in the elderly was negatively associated with the guidelines adherence of antibiotiсs prescriptions. These criteria should be considered to optimize antibiotics prescriptions in elderly patients.

Relationship Between Future Thinking and Prospective Memory in Alzheimer's Disease.

Background: Future thinking and prospective memory are two cognitive processes oriented toward the future and reliant on the ability to envision oneself in future scenarios. Objective: We explored the connection between future thinking and prospective memory in individuals with Alzheimer's disease (AD). Methods: We invited both AD participants and control participants to engage in event-based prospective memory tasks (e.g., "please hand me this stopwatch when I inform you there are 10 minutes remaining") and time-based prospective memory tasks (e.g., "close the book you are working on in five minutes"). Additionally, we asked participants to engage in a future thinking task where they imagined upcoming events. Results: Analysis revealed that AD participants exhibited lower performance in both prospective memory tasks and future thinking compared to the control group. Importantly, we identified significant positive correlations between the performance on event- and time-based prospective memory tasks and future thinking abilities among AD participants. Conclusions: These findings underscore the connection between the decline in both prospective memory domains and the ability to envision future events in individuals with AD. Our results also shed light on the challenges AD individuals face when trying to project themselves into the future to mentally pre-experience upcoming events.

[Practical review of driving in older patient: from theory to practice]. / La conduite chez la personne âgée, de la théorie à la pratique.

As the French population is ageing, the number of older people on the road is increasing all the time. For many older adults, this everyday activity remains an important way of maintaining their independence. Putting this right into question on the sole basis of age can be seen as a particularly stigmatising measure. However, this population is particularly vulnerable on the road. While behavioural factors are frequently involved in young adults, driving errors seem to be more frequently the main mechanism in older people. Driving is a succession of complex tasks that can be affected by ageing and the presence of pathologies (cognitive decline, sensory deficiencies or cardiovascular conditions that have not stabilised, etc.). As these medical conditions increase with age, it is important that healthcare professionals identify high-risk situations. When it is required, the professionals should assist patients to stop driving and find alternatives. Maintaining the mobility and ensure safety for older adults on the road remain challenging for the community. In this article, we discuss the issues surrounding the maintenance of driving in older adults. We also discuss the appropriate way to help patients stop driving when necessary.

ChatGPT as a Diagnostic Aid in Alzheimer's Disease: An Exploratory Study.

Background: The potential of ChatGPT in medical diagnosis has been explored in various medical conditions. Objective: We assessed whether ChatGPT can contribute to the diagnosis of Alzheimer's disease (AD). Methods: We provided ChatGPT with four generated cases (mild, moderate, or advanced stage AD dementia, or mild cognitive impairment), including descriptions of their complaints, physical examinations, as well as biomarker, neuroimaging, and neuropsychological data. Results: ChatGPT accurately diagnosed the test cases similarly to two blinded specialists. Conclusions: While the use of generated cases can be a limitation to our study, our findings demonstrate that ChatGPT can be a useful tool for symptom assessment and the diagnosis of AD. However, while the use of ChatGPT in AD diagnosis is promising, it should be seen as an adjunct to clinical judgment rather than a replacement.

The Pupil Knows: Pupil Dilation Indexes and Their Inhibitory Ability in Normal Aging.

Pupil dilation is considered an index of cognitive effort, as the pupil typically dilates as the cognitive load increases. In this paper, we evaluated whether older adults demonstrate increased pupil size when performing tasks requiring cognitive inhibition. We invited 44 older and 44 younger adults to perform the Stroop task while their pupil dilation was recorded with eye-tracking glasses. The dependent variables were the number of accurate responses on the Stroop task as well as pupil size in the three conditions of the task (i.e., color naming, word reading, and the interference condition). The results demonstrated less accurate responses in the interference condition than in the color-naming or word-reading conditions, in both older and younger adults. Critically, larger pupil dilation was observed in the interference condition than in the color-naming and word-reading conditions, in both older and younger adults. This study demonstrates that pupil dilation responds to cognitive effort in normal aging, at least in the interference condition of the Stroop task.

ChatGPT's dance with neuropsychological data: A case study in Alzheimer's disease.

Artificial intelligence continues to revolutionize the medical and scientific field, especially with the release of ChatGPT. We assessed whether it provides an accurate interpretation of neuropsychological screening. We provided ChatGPT with the neuropsychological data of a patient with mild Alzheimer's Disease and invited it and two neuropsychologists to interpret the data. While ChatGPT provided an accurate interpretation of scores on each of the neuropsychological tests, it did not use standardized scores and did not specify the cognitive domain that may be most impaired. In contrast, the neuropsychologists used standardized scores to determine that the patient was mainly suffering from memory decline. While ChatGPT may succeed in the general interpretation of neuropsychological testing, at least in patients with Alzheimer's Disease, it still cannot create a pattern of scores across different tests to better specify the nature of cognitive impairment.