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.

[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.

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.

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.

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.

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.

Tau expression and phosphorylation in enteroendocrine cells.

Background and objective: There is mounting evidence to suggest that the gut-brain axis is involved in the development of Parkinson's disease (PD). In this regard, the enteroendocrine cells (EEC), which faces the gut lumen and are connected with both enteric neurons and glial cells have received growing attention. The recent observation showing that these cells express alpha-synuclein, a presynaptic neuronal protein genetically and neuropathologically linked to PD came to reinforce the assumption that EEC might be a key component of the neural circuit between the gut lumen and the brain for the bottom-up propagation of PD pathology. Besides alpha-synuclein, tau is another key protein involved in neurodegeneration and converging evidences indicate that there is an interplay between these two proteins at both molecular and pathological levels. There are no existing studies on tau in EEC and therefore we set out to examine the isoform profile and phosphorylation state of tau in these cells. Methods: Surgical specimens of human colon from control subjects were analyzed by immunohistochemistry using a panel of anti-tau antibodies together with chromogranin A and Glucagon-like peptide-1 (two EEC markers) antibodies. To investigate tau expression further, two EEC lines, namely GLUTag and NCI-H716 were analyzed by Western blot with pan-tau and tau isoform specific antibodies and by RT-PCR. Lambda phosphatase treatment was used to study tau phosphorylation in both cell lines. Eventually, GLUTag were treated with propionate and butyrate, two short chain fatty acids known to sense EEC, and analyzed at different time points by Western blot with an antibody specific for tau phosphorylated at Thr205. Results: We found that tau is expressed and phosphorylated in EEC in adult human colon and that both EEC lines mainly express two tau isoforms that are phosphorylated under basal condition. Both propionate and butyrate regulated tau phosphorylation state by decreasing its phosphorylation at Thr205. Conclusion and inference: Our study is the first to characterize tau in human EEC and in EEC lines. As a whole, our findings provide a basis to unravel the functions of tau in EEC and to further investigate the possibility of pathological changes in tauopathies and synucleinopathies.

How Do Women and Men Look at the Past? Large Scanpath in Women during Autobiographical Retrieval-A Preliminary Study.

While research has consistently demonstrated how autobiographical memory triggers visual exploration, prior studies did not investigate gender differences in this domain. We thus compared eye movement between women and men while performing an autobiographical retrieval task. We invited 35 women and 35 men to retrieve autobiographical memories while their gaze was monitored by an eye tracker. We further investigated gender differences in eye movement and autobiographical specificity, that is, the ability to retrieve detailed memories. The analysis demonstrated shorter fixations, larger duration and amplitude of saccades, and higher autobiographical specificity in women than in men. The significant gender differences in eye movement disappeared after controlling for autobiographical specificity. When retrieving autobiographical memory, female participants generated a large scan with short fixation and high saccade amplitude, while male participants increased their fixation duration and showed poorer gaze scan. The large saccades in women during autobiographical retrieval may constitute an exploratory gaze behavior enabling better autobiographical memory functioning, which is reflected by the larger number of autobiographical details retrieved compared to men.

Nocturnal hypoglycemia is underdiagnosed in older people with insulin-treated type 2 diabetes: The HYPOAGE observational study.

BACKGROUND: There is a lack of real-life data regarding the frequency and predictive factors of hypoglycemia in older patients with type 2 diabetes (T2D). This study aimed to determine the frequency and predictors of hypoglycemia in older patients with insulin-treated T2D. METHODS: This prospective multicenter study included 155 insulin-treated T2D patients aged 75 years and older with ≥2 self-monitoring of blood glucose (SMBG) daily controls. Participants underwent a geriatric and diabetic assessment and received ambulatory blinded continuous glucose monitoring (CGM) for 28 consecutive days with FreeStyle Libre Pro® sensor. Study population (n = 141) has >70% CGM active time. Multivariable logistic regressions were used to identify factors associated with SMBG confirmed hypoglycemia (≥70 mg/dL) and with nocturnal level 2 time below range (glucose concentration <54 mg/dL during ≥15 consecutive min between 0.00 and 6.00 am). RESULTS: The mean age of the 141 analyzed patients was 81.5 ± 5.3 years and 56.7% were male. The mean baseline HbA1c was 7.9% ± 1.0%. After geriatric assessment, 102 participants (72.3%) were considered as complex and 39 (27.7%) as healthy. The primary endpoint (confirmed SMBG <70 mg/dL) occurred in 37.6% patients. In multivariable analysis, the risk of SMBG-confirmed hypoglycemia was positively associated with a longer duration of diabetes (OR (+1 year) =1.04, (1.00-1.08), p = 0.04) and glycemic variability assessed by CGM (CV %) (OR (+1%) = 1.12, [1.05-1.19], p = <0.001). Nighty-two patients (65.2%) experienced nocturnal time in hypoglycemia (i.e., <54 mg/dL during ≥15 consecutive min between midnight and 6 a.m.). In multivariable analyses, cognitive impairment (OR: 9.31 [2.59-33.4]), heart failure (OR: 4.81 [1;48-15.6]), and depressive disorder (OR: 0.19 [0.06-0.53]) were associated with nocturnal time in hypoglycemia. CONCLUSION: Nocturnal hypoglycemia is very common and largely underdiagnosed in older patients with insulin-treated T2D. CGM is a promising tool to better identify hypoglycemia and adapt diabetes management in this population.

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.

[Evaluation of ophthalmological follow-up of patients over 65 years old in primary care]. / Évaluation du suivi ophtalmologique des patients de plus de 65 ans en médecine générale.

Visual disorders are often under-diagnosed and under-treated in older patients. The main objective was to evaluate the percentage of patients having an ophthalmological follow-up corresponding to the recommendations of the Syndicat national des ophtalmologistes de France (SNOF). This prospective observational multicentre study included all patients aged 65 years or older presenting to their general practitioner in two medical practices from May to October 2021. Of the 113 patients included, 86 (76,1 %) had adequate ophthalmological follow-up, 14 consulted an ophthalmologist, and a therapeutic decision was made for nine patients. Follow-up of patients was generally as recommended. Screening for visual disorders for patients with no recent follow-up was beneficial. This screening must be integrated into a global approach, as the Integrated Care for Older People (ICOPE) of the World Health Organization (WHO), in order to be more relevant and effective.

[How potentially inapropriate are psychotropic drugs prescribing in acute psychiatric unit for the elderly? Results from a large multicentric audit in France]. / Prescription inadaptée de psychotropes en unités de psychiatrie aiguë pour personnes âgées : une étude transversale multicentrique.

Adverse drug reactions (ADRs) are a major public health issue, especially when it comes to the elderly. Potentially inappropriate prescribing (PIP) are one of the causes of ADRs in older people. A PIP can be defined as a prescription for which the benefit/risk ratio is unfavourable compared to other therapeutic alternatives. Psychotropic drugs are the second highest risk class for ADRs in the elderly. In order to reduce the prevalence of PIP, prescription assistance tools have been created. An inventory of PIP of psychotropic drugs in older patients hospitalized in psychiatry units was carried out in a French regional setting in 2019. A criteria grid was established based on 2 tools: STOPP/START criteria and Laroche's list adapted to French practice. This grid targeted each class of psychotropic drugs, drugs with a high anticholinergic burden and non-recommended combinations of psychotropic drugs. Three hundred forty-seven patients were included. A high prevalence of PPI was found for each class of psychotropic drugs. The highest prevalence of PPI was found among benzodiazepines (90.3%): long-term prescription, long half-life drugs, respiratory insufficiency or cognitive impairment condition. 56.5% of the subjects had a not-recommended combination of psychotropic drugs (prescription of drugs of the same pharmacotherapeutic class), 26% had a PIP of antipsychotics: prescription for insomnia, use of phenothiazine, 11.8% of drugs with anticholinergic properties and 7.4% of antidepressants: especially prescription of tricyclic drugs. These results obtained on a large population underline the interest of considering the specificities of prescriptions in the elderly. It shows both the interest and the limits of the current criteria defining the PIP in the context of a hospitalization in psychiatry for an acute disorder in elderly subjects.

Factors Associated with Dual-Fluency Walk Speed Improvement after Rehabilitation in Older Patients.

Walk speed measured under dual-task conditions (neurocognitive tasks) could reflect patient performance in real-life. Rehabilitation programs are effective in increasing walk speed, but few studies have evaluated the associations between geriatric factors and rehabilitation efficacy under dual-task conditions. Our objective was to investigate the association between geriatric factors and an increase in dual-task walk speed (threshold of 0.1 m/s), after a multidisciplinary rehabilitation program. We performed a retrospective cohort study that included patients aged 75 years and over, who underwent a complete rehabilitation program and who had a neurocognitive assessment at baseline. The primary outcome was the increase in the dual-task (fluency verbal task) walking speed between pre- and post-rehabilitation assessments. In this study, 145 patients were included, with a mean age of 83.6 years old. After rehabilitation, dual-task walk speed increase in 62 (43%) patients. In multivariate analysis, the following factors were associated with an increase in dual-task walk speed: IADL (OR 2.50, 95% CI [1.26; 4.94], p = 0.009), vitamin D level (OR 0.83, 95% CI [0.72; 0.95], p = 0.008), severe sarcopenia (OR 0.00, 95% CI [0.00; 0.32], p = 0.016), depression (OR 15.85, 95% CI [1.32; 190.40], p = 0.029), number of drugs (OR 1.41, 95% CI [1.04; 1.92], p = 0.027), initial dual-fluency walk speed (OR 0.92, 95% CI [0.86; 0.98], p = 0.014) and time interval between initial and final assessments (OR 0.98, 95% CI [0.96; 1.00], p = 0.06). Identifying patients that are less resilient to rehabilitation may promote a centered-patient approach for an individualized and optimized rehabilitation care.

The talking eyes: Pupillometry to index verbal fluency in normal aging.

BACKGROUND: Verbal fluency tasks are widely used to assess cognitive and linguistic abilities in older adults. In this study, we investigated whether pupillometry can be used to measure verbal fluency in healthy older adults. METHODS: We invited 45 older adults (Mean age = 66.55 years, SD = 4.32) to perform a verbal fluency task, which involves generating as many words as possible beginning with the letter "P" for a duration of one minute. We also invited participants to perform a control task, which involves counting aloud for one minute. In both tasks, we recorded pupil activity with eye-tracking glasses. RESULTS: Analysis demonstrated a larger pupil size during the verbal fluency condition than in the counting condition. Significant positive correlations were observed between pupil size and correct responses on the verbal fluency task. CONCLUSION: The larger pupil size during the verbal fluency condition can be attributed to the cognitive load inherent in the verbal fluency task and/or to the ability of older adults to produce correct answers on this task. Our study demonstrates how pupillometry can be used as an ecological physiological assessment of not only verbal fluency, but also linguistic ability in general, in normal aging.

Does Sex Matter? High Semantic Autobiographical Retrieval in Women and Men With Alzheimer's Disease.

The decline of autobiographical memory in Alzheimer's disease (AD) is mainly characterized by overgenerality. While there is a large body of research on autobiographical overgenerality in AD, this research has mainly assessed retrieval with a dichotomy between specific vs. general retrieval. To go beyond this dichotomy, we assessed several degrees of autobiographical specificity in patients with AD, namely, we assessed specific vs. categoric vs. extended vs. semantic retrieval. We also assessed sex differences regarding these degrees of autobiographical specificity. We invited patients with mild AD and control participants to complete sentences (e. g., "When I think back to/of…") with autobiographical memories. Memories were categorized into specific, categoric, extended, or semantic memories. Results demonstrated more semantic than specific, categoric or extended memories in men and women with AD. In control participants, analysis demonstrated more specific than categoric, extended, and semantic memories in men and women. Also, no significant differences were observed between women and men with AD, or between control women and men, regarding specific, categoric, extended, and semantic memoires. This study offers not only a nuanced analysis of autobiographical specificity in patients with mild AD, but also an original analysis regarding this specificity by sex.

"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.

Empathy of individuals with Alzheimer's disease (AD) toward other AD patients.

BACKGROUND: The objective of this study was twofold. We assessed whether individuals with Alzheimer's disease (AD) demonstrate higher empathy toward people with the same disorder. We also assessed whether empathy may enhance the recognition of these peoples' faces. METHOD: Twenty-seven mild AD participants and 30 healthy older adults were invited to retain faces depicting either people diagnosed with AD or healthy people. Participants were also invited to rate their empathy toward all faces. RESULTS: Although AD participants reported higher empathy for "AD-labeled" than for "healthy" faces, recognition was similar for both categories of faces. Healthy older adults also reported higher empathy for "AD-labeled" than for "healthy" faces. However, they demonstrated higher recognition for "healthy" than for "AD-labeled" faces. CONCLUSIONS: Although our paper shows no effect of empathy on face recognition in AD, it provides a clinically relevant finding: individuals with mild AD can demonstrate significant empathy toward people with the same medical condition.

Is the Snoezelen method a non-pharmacological alternative for patients with neurocognitive disorders? / La méthode Snoezelen : une alternative thérapeutique chez les patients ayant des troubles cognitifs ?

Neuropsychiatric disorders are one of the frequent complications of neurocognitive disease, and have an impact on the quality of life of patients and caregivers. Non-phamacologic interventions are recommended as first-line treatment. The Snoezelen method is a multisensory stimulation method based on the assumption that acting on sensoriality can improve neuropsychiatric symptoms and thus quality of life, but its level of evidence is controversial. To explore this, we performed a systematic literature review of randomized controlled articles focusing on the use of the Snoezelen method in patients with cognitive disorders. Eighteen studies were included. The clinical outcomes studied were multiple (behavior, mood, cognition, functional capacities and biomedical parameters). When the Snoezelen method was compared to the "standard activities" group, it appears to be effective on short-term behavior. This was more negligible when the method was compared to others non-pharmacological interventions. Although the Snoezelen method could be effective on mood, cognition, and functional abilities, its level of evidence remains low. Furthers mixed studies (quantitative and qualitative) would be an interesting approach to delve into this topic in the most holistic way by integrating the patients, the caregivers and the cost of the method.

La prise en soin des symptômes neuropsychiatriques de patients ayant des troubles neurocognitifs est basée sur des traitements non médicamenteux. Certains auteurs suggèrent que la méthode Snoezelen pourrait être une alternative thérapeutique. L'objectif de cette revue de littérature était de faire une recherche systématique des essais contrôlés et randomisés ayant analysé l'effet de la méthode Snoezelen sur les patients âgés ayant des troubles cognitifs. Le processus de sélection a permis d'inclure 18 études, ayant des méthodologies hétérogènes. Dans plusieurs études, la méthode Snoezelen pourrait avoir un effet bénéfique, à court terme, sur les troubles du comportement, sur l'humeur, la cognition, ou les capacités fonctionnelles. Cependant, la méthode Snoezelen ne semblait pas être supérieure à d'autres interventions non médicamenteuses et certaines études montraient des résultats discordants. Finalement, le niveau de preuve d'efficacité de la méthode Snoezelen reste faible et des études mixtes (quantitatives et qualitatives) seraient intéressantes à mener pour évaluer l'intérêt de la méthode Snoezelen sur des profils spécifiques de patients ayant des troubles neurocognitifs.