Cognitive Impairment Symptoms Research Articles

Exploring Huntington's Disease Diagnosis via Artificial Intelligence Models: A Comprehensive Review.

Huntington's Disease (HD) is a devastating neurodegenerative disorder characterized by progressive motor dysfunction, cognitive impairment, and psychiatric symptoms. The early and accurate diagnosis of HD is crucial for effective intervention and patient care. This comprehensive review provides a comprehensive overview of the utilization of Artificial Intelligence (AI) powered algorithms in the diagnosis of HD. This review systematically analyses the existing literature to identify key trends, methodologies, and challenges in this emerging field. It also highlights the potential of ML and DL approaches in automating HD diagnosis through the analysis of clinical, genetic, and neuroimaging data. This review also discusses the limitations and ethical considerations associated with these models and suggests future research directions aimed at improving the early detection and management of Huntington's disease. It also serves as a valuable resource for researchers, clinicians, and healthcare professionals interested in the intersection of machine learning and neurodegenerative disease diagnosis.

Exploring language performance in people with mild cognitive impairment and Alzheimer's disease: a prospective longitudinal study

Background/Aims Language changes are the earliest signs and symptoms of mild cognitive impairment and Alzheimer's disease. The aim of this study was to explore the language difference performance between people with mild cognitive impairment, people with Alzheimer's disease and healthy individuals as a control group. To accomplish this aim, the language profile of both mild cognitive impairment and Alzheimer's disease needs to be characterised to determine which feature is more affected by both mild cognitive impairment and Alzheimer's disease among expressive language, receptive language, executive function and memory performance. Methods This case-control prospective study involved 90 participants. The Mini-Mental Status Examination and the Functional Assessment Staging Tool were used to classify the participants into three groups: people with mild cognitive impairment, people with Alzheimer's disease and healthy individuals as a control group. Then, the language performance of patients in the mild cognitive impairment and Alzheimer's disease groups was investigated and compared with those of the control group by using the Barnes Language Assessment. The groups were reassessed 6 months later to see if there was any change in language ability. Results The results showed that the mild cognitive impairment group and Alzheimer's disease group had significant decreases in expressive language (P>0.01), executive function (P>0.01), receptive language (P>0.01) and memory skills (P>0.01) from baseline to the reassessment at 6 months. Conclusions Language deficits, especially expressive language deficits, could appear before impairment in executive function, receptive language and verbal episodic memory in participants with mild cognitive impairment or Alzheimer's disease. Speech and language therapists can use the findings of this study to design and implement treatment programmes.

Neuropsychiatric symptoms are Predictors of Disturbed Sleep in Mexican American Caregivers

AbstractBackgroundCaregivers of people living with dementia are more likely to experience disturbed sleep compared to non‐caregivers. Mexican‐Americans may be especially at risk due to low rates of nursing home use even in advanced dementia, when behavioral symptoms are most apparent. Few studies have evaluated predictors of disturbed sleep in this high‐risk group.MethodUsing data from the 2015 wave of the Hispanic Established Population for Epidemiologic Study of the Elderly, a representative sample of older Mexican‐Americans and their caregivers in the southwestern United States (n = 460), we examined the association of care recipient neuropsychiatric symptoms with disturbed sleep in caregivers. Care recipients’ behavioral symptoms of cognitive decline were assessed using the caregiver‐reported Neuropsychiatric Inventory. We examined caregivers’ depressive symptoms as an additional stressor. Potential “buffers” against sleep disturbances included communal support (neighbor, church, social services) and respite care. Caregivers were classified as having “highly disturbed sleep” if they reported disturbed sleep three or more days a week, and were compared to caregivers with “non‐highly disturbed sleep” (reported disturbed sleep less than three days a week). We used multivariable logistic regression to examine the association between behavioral symptoms and highly disturbed sleep, controlling for demographic factors and care buffers.ResultCaregivers in the sample were predominantly spouses or adult children of their care recipients. They had a mean age of 59.7 and7 8% were women. Care recipients were a mean age of 90 and 65% were women. Caregivers with disturbed sleep (12% of the sample) reported significantly more care recipient NPI symptoms, distress from symptoms, and more depressive symptoms. In the regression model accounting for all predictors, the number of NPI symptoms and depressive symptoms were associated with higher odds of disturbed sleep, while communal support was associated with lower odds of disturbed sleep. Use of respite care did not show associations.ConclusionBehavioral symptoms of cognitive impairment are associated with sleep disturbance in Mexican American caregivers. Though respite has been described as a crucial resource for caregiver sleep health, communal supports were more significantly associated with sleep l. These results should inform the development of culturally‐competent resources for Mexican‐Americans.

NG‐001: A novel multi‐domain digital cognitive intervention for cognitive symptoms in mild cognitive impairment

AbstractBackgroundMild cognitive impairment (MCI) is a prodromal stage of Alzheimer’s disease that offers a window for early intervention prior to dementia onset. The cognitive impairment observed in MCI includes declines across several cognitive domains, including memory, processing speed, and executive function. Emerging evidence supports a multidomain intervention to improve cognitive performance. Therefore, we aim to investigate the utility of a novel, scalable multi‐domain digital intervention as a therapeutic solution to prevent or reverse cognitive decline.Method30 amnestic MCI patients were enrolled in a pilot open‐label clinical trial of a 10‐week digital therapeutic intervention using NG‐001 delivered via a tablet. 27 participants completed the trial and their data were analyzed. NG‐001 consisted of weekly 1‐hour trainings spread across several domains: cognitive games; physical exercise; mindfulness (e.g., yoga and meditation); health literacy; and reminiscence therapy. The outcome composite scores were calculated from the Neuropsychological Test Battery including Overall Cognition, Processing Speed, Executive Functioning, Overall Memory as well as Immediate and Delayed Memory. Composites were calculated into Z‐scores based on normative data from age and education‐adjusted reference groups. Changes in the Z‐scores were then assessed using paired Wilcoxon signed ranked tests (two‐tailed) and the effect size was calculated using Hedges’ g.ResultCompared to baseline, at post‐intervention, MCI patients showed significant improvements in Overall Cognition (‐0.440 to ‐0.213, g = 0.352), Overall Memory (‐0.587 to ‐0.132, g = 0.407), Immediate Memory (‐0.549 to ‐0.030, g = 0.512) and Delayed Memory (‐0.626 to ‐0.233, g = 0.305). There were no significant changes in Processing Speed or in Executive Functioning (ps > .05).ConclusionNG‐001 significantly improved memory (both immediate and delayed) for amnestic MCI patients, indicating its potential as a form of digital therapeutics for early intervention of memory impairment in MCI. Further research is needed to investigate the mechanisms involved in this improvement, and whether modifications can be made to extend its facilitatory effect to other cognitive domains such as executive functioning and language.

NG‐001: A novel multi‐domain digital cognitive intervention for cognitive symptoms in mild cognitive impairment

AbstractBackgroundMild cognitive impairment (MCI) is a prodromal stage of Alzheimer’s disease that offers a window for early intervention prior to dementia onset. The cognitive impairment observed in MCI includes declines across several cognitive domains, including memory, processing speed, and executive function. Emerging evidence supports a multidomain intervention to improve cognitive performance. Therefore, we aim to investigate the utility of a novel, scalable multi‐domain digital intervention as a therapeutic solution to prevent or reverse cognitive decline.Method30 amnestic MCI patients were enrolled in a pilot open‐label clinical trial of a 10‐week digital therapeutic intervention using NG‐001 delivered via a tablet. 27 participants completed the trial and their data were analyzed. NG‐001 consisted of weekly 1‐hour trainings spread across several domains: cognitive games; physical exercise; mindfulness (e.g., yoga and meditation); health literacy; and reminiscence therapy. The outcome composite scores were calculated from the Neuropsychological Test Battery including Overall Cognition, Processing Speed, Executive Functioning, Overall Memory as well as Immediate and Delayed Memory. Composites were calculated into Z‐scores based on normative data from age and education‐adjusted reference groups. Changes in the Z‐scores were then assessed using paired Wilcoxon signed ranked tests (two‐tailed) and the effect size was calculated using Hedges’ g.ResultCompared to baseline, at post‐intervention, MCI patients showed significant improvements in Overall Cognition (‐0.440 to ‐0.213, g = 0.352), Overall Memory (‐0.587 to ‐0.132, g = 0.407), Immediate Memory (‐0.549 to ‐0.030, g = 0.512) and Delayed Memory (‐0.626 to ‐0.233, g = 0.305). There were no significant changes in Processing Speed or in Executive Functioning (ps > .05).ConclusionNG‐001 significantly improved memory (both immediate and delayed) for amnestic MCI patients, indicating its potential as a form of digital therapeutics for early intervention of memory impairment in MCI. Further research is needed to investigate the mechanisms involved in this improvement, and whether modifications can be made to extend its facilitatory effect to other cognitive domains such as executive functioning and language.

NG‐001: A novel multi‐domain digital cognitive intervention for neuropsychiatric symptoms in mild cognitive impairment

AbstractBackgroundNeuropsychiatric symptoms (NPS) are increasingly recognized as early non‐cognitive manifestations of patients at‐risk of dementia and are associated with accelerated cognitive decline. While cognitive stimulation may be an effective intervention in improving NPS and quality of life of patients and their caregivers, there is a need for a digital intervention that is accessible and scalable so that the benefits of improving behavioral outcomes can be attained on a larger scale. Here, we studied the effectiveness of a novel multi‐domain digital cognitive intervention on NPS among patients with mild cognitive impairment (MCI).MethodWe conducted a pilot 10‐week open‐label clinical trial of 30 MCI patients using the NG‐001, a multi‐domain digital intervention. NG‐001 is a digital program which consists of weekly 1‐hour training in several domains: cognitive games; physical exercise; mindfulness (e.g., yoga and meditation); health literacy; and reminiscence therapy. Participants completed the Depression Anxiety Stress Scale (DASS) and the Mild‐Behavioral Impairment‐Checklist (MBI‐C) at baseline and at the end of the trial. Changes in DASS and MBI‐C scores were assessed using paired Wilcoxon signed ranked tests (two‐tailed) and effect sizes were reported using Hedges’ g.ResultMCI patients showed significant improvements in depression (4.643 vs. 3.214, g = 0.228), anxiety (6.357 vs. 3.786, g = 0.440) and stress (7.786 vs. 5.429, g = 0.356) scores as measured by DASS with NG‐001 intervention (Figure 1). MCI patients also showed significant improvements in MBI‐C total scores (3.29 vs. 1.43, g = 0.47), the apathy sub‐domain scores (0.96 vs. 0.21, g = 0.54), and the affect sub‐domain scores (1.25 vs. 0.43, g = 0.47) with NG‐001 intervention (Figure 2). Importantly, there was high compliance among the participants who completed the full 10‐week intervention.ConclusionA 10‐week multi‐domain digital intervention with NG‐001 reduces the severity of NPS among MCI patients. A longer trial with a control arm is needed to further determine the efficacy of NG‐001 for NPS among MCI patients.

P139: Psychotherapy for Anxiety and Anxiety related symptoms in Mild Cognitive Impairment - A Case Treated with Morita Therapy-

Morita Therapy is a psychotherapy which originated in Japan. Conventionally, it had been applied to ‘neurosis’. The patients who have anxiety symptoms make various efforts in order to be free from the unpleasant emotion. Morita Therapy (1) does not try to eliminate anxiety and its symptoms and builds the patients’ attitude to leave these symptoms as a natural course, and (2) to focus on the feeling that they should aspire to enhancing their life and to encourage them to exert their lust for life. The authors presumed that this concept can be applied to anxiety symptoms in patients with mild cognitive impairment (MCI) and attempts to intervene. This case is for a male patient aged 74 years old with MCI with the complaint of subjective cognitive impairments. He had severe anxiety for his own cognitive impairment and recognized a severe decrease of Quality of Life (QOL) due to worrying about his own excessive anxiety. The authors implemented the therapeutic approach to address his anxiety and encouraged him to improve his QOL by accepting the anxiety, not excluding it. During the therapeutic process, various problems were evident, such as the caregiver’s excessive fear of dementia, so education about the nature of dementia was provided to dispel the stigma for the family members. As a result, the patient’s anxiety was decreased, and his daily activities were observed in spite of his subjective cognitive decline. This case suggested that Morita therapy was effective for anxiety symptoms in patients with MCI.

Anosognosia is associated with increased prevalence and faster development of neuropsychiatric symptoms in Mild Cognitive Impairment

AbstractBackgroundBoth the loss of awareness for cognitive decline (a.k.a anosognosia) and neuropsychiatric symptoms (NPS) are commonly seen in patients with Alzheimer’s disease (AD) dementia, even in the prodromal stages. Anosognosia and NPS may negatively affect caregiver burden and patient’s activities of daily living. Despite the high impact of these symptoms on patients and their caregivers, our knowledge of how they develop across the AD spectrum is limited. Here, we explored the cross‐sectional and longitudinal associations between anosognosia and NPS in individuals with mild cognitive impairment (MCI).MethodWe included 310 participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) with a baseline Clinical Dementia Rating global score of 0.5. Everyday Cognition (ECog) questionnaire scores were used to measure complaints from participants and study‐partners at baseline and annually over a mean of 4 years (SD = 3). Anosognosia was defined as the study‐partner having an ECog score ≥2.5/4 and the participant having an ECog score ≤2.5/4 on their baseline measure and their last observation and without having more than 2 consecutive deviating observations during the follow‐up period. The 12 study‐partner‐rated Neuropsychiatric Inventory items determined the presence or absence of specific NPS (see Table 1). The Mini‐Mental State Examination (MMSE), an assessment used to screen for cognitive impairment, was administered annually. Survival analyses were performed to analyze the rate of appearance of NPS over time in individuals with and without anosognosia.ResultSixty participants displayed anosognosia, while 250 did not. At baseline, groups had similar lengths of follow‐up. Participants with anosognosia had lower MMSE scores and a higher proportion of amyloid positivity (see Table 1). At baseline, the frequency of agitation and disinhibition was higher in the anosognosia group. Survival analyses showed earlier onset of all NPS in the anosognosia group (see Figure 1). Specifically, aberrant motor behavior, irritability, disinhibition, apathy, agitation, and hallucinations were highly significant.ConclusionLoss of awareness for cognitive decline is associated with greater frequency and faster onset of NPS over time in participants with MCI. These results support the hypothesis of a potential common underlying neurophysiological process, a finding that needs to be addressed further in future studies.

NG‐001: A novel multi‐domain digital cognitive intervention for neuropsychiatric symptoms in mild cognitive impairment

AbstractBackgroundNeuropsychiatric symptoms (NPS) are increasingly recognized as early non‐cognitive manifestations of patients at‐risk of dementia and are associated with accelerated cognitive decline. While cognitive stimulation may be an effective intervention in improving NPS and quality of life of patients and their caregivers, there is a need for a digital intervention that is accessible and scalable so that the benefits of improving behavioral outcomes can be attained on a larger scale. Here, we studied the effectiveness of a novel multi‐domain digital cognitive intervention on NPS among patients with mild cognitive impairment (MCI).MethodWe conducted a pilot 10‐week open‐label clinical trial of 30 MCI patients using the NG‐001, a multi‐domain digital intervention. NG‐001 is a digital program which consists of weekly 1‐hour training in several domains: cognitive games; physical exercise; mindfulness (e.g., yoga and meditation); health literacy; and reminiscence therapy. Participants completed the Depression Anxiety Stress Scale (DASS) and the Mild‐Behavioral Impairment‐Checklist (MBI‐C) at baseline and at the end of the trial. Changes in DASS and MBI‐C scores were assessed using paired Wilcoxon signed ranked tests (two‐tailed) and effect sizes were reported using Hedges’ g.ResultMCI patients showed significant improvements in depression (4.643 vs. 3.214, g = 0.228), anxiety (6.357 vs. 3.786, g = 0.440) and stress (7.786 vs. 5.429, g = 0.356) scores as measured by DASS with NG‐001 intervention (Figure 1). MCI patients also showed significant improvements in MBI‐C total scores (3.29 vs. 1.43, g = 0.47), the apathy sub‐domain scores (0.96 vs. 0.21, g = 0.54), and the affect sub‐domain scores (1.25 vs. 0.43, g = 0.47) with NG‐001 intervention (Figure 2). Importantly, there was high compliance among the participants who completed the full 10‐week intervention.ConclusionA 10‐week multi‐domain digital intervention with NG‐001 reduces the severity of NPS among MCI patients. A longer trial with a control arm is needed to further determine the efficacy of NG‐001 for NPS among MCI patients.

Relationship between occupation and cognitive performance in patients with cognitive impairment. Preliminary study

AbstractBackgroundPrevious studies showed the protective effect of cognitive reserve for the development of cognitive impairment and dementia symptoms. Some factors have been postulated that may influence cognitive reserve, including education, participation in cognitively stimulating activities, and occupation. It has been observed that certain occupations have better cognitive performance and different professions may generate better functioning in certain cognitive domains than others. The aim of this study is to assess whether there is greater strength in certain cognitive domains related to the occupations of patients with subjective memory complaints or mild cognitive impairment diagnosis.MethodRetrospective observational study with patients under follow‐up in a memory clinic in Buenos Aires, Argentina. Patients with >17 education years, > 50 years with a diagnosis of subjective memory complaint and/or mild cognitive impairment of any origin were included. Subjects with dementia were excluded. The occupations were classified according to the ISCO‐88 (2008 International Labor Organization) utilizing professionals’ subcategory. A complete cognitive evaluation was performed in all the patients, including memory, attention, language, executive functions, and visuospatial domains. For the statistical analysis, the z scores of the results of the different cognitive tests were used and parametric student`s‐t tests were performed using the Graphpad software,ResultA total of 57 patients from our center were included to date. The mean age was 71 (55‐85), years of education 19 (17‐25) and a total of 35 (61%) women. The mean of Addenbrooke’s Cognitive Examination (ACE) was 91.3 (82‐99). The predominant occupation was in the health category with a total of 24 (42%) patients. No statistically significant differences were obtained in the values of the different cognitive tests of each occupational category and the value of the total population.ConclusionThe study has not shown significant differences between specific cognitive variables and occupation in patients with cognitive impairment. However, a larger number of subjects would be needed to support this statement. It is important to note that extra‐work activities of patients that can also influence their cognitive performance have not been taken into account.

Personalized nutritional ketosis through a whole‐food low‐carb diet, medium chain triglycerides, and other ketogenic strategies for people with mild cognitive impairment and Alzheimer’s disease

AbstractInsulin resistance with abnormal brain glucose uptake, a brain‐energy gap, and neuroinflammation are common in the aging brain and are exaggerated in people with Alzheimer’s disease (AD) and in some people with MCI (Cunnane Nature Reviews Drug Discovery 2020). Ketones are an alternative fuel for the brain and ketone uptake is normal in brain regions affected by abnormal glucose uptake in AD (Castellano J Alzheim Dis 2015). Ketones are anti‐inflammatory (Kim Frontiers Immunol 2022) and lessen beta amyloid plaques, tau tangles, and anxiety in animal models (Kashiwaya PNAS 2000; Wu FASEB 2020). Increased brain energy from ketones has been demonstrated using PET imaging in clinical trials of MCT oil (Fortier Alz Dementia 2021), ketogenic diet (KD) (Neth Neurobiol Aging 2020), and exercise (Vandenberghe Appl Physiol Nutr Metab 2019). Recent studies report cognitive and/or other clinical improvements in MCI and/or AD with KD (Brandt J Alzheimers Dis 2019), modified Mediterranean KD (Neth Neurobiol Aging 2020), KD with MCT oil (Taylor Alzheimers Dement 2017), KD with coconut oil in keto study diet recipes (Phillips Alz Research & Therapy 2021), MCT oil with habitual diet (Reger Neurobio Ageing 2004; Constantini Nutri Metab 2009; Maynard Neuropsych Disease Treat 2013; Abe J Nutr Sci Vitaminol 2017; Abe J Nutr 2016; Xu et al. Clin Nutr 2020; Fortier Alz & Dementia 2021), and coconut oil with habitual diet (De la Rubia Orti Nutr Hosp 2017). Case reports of people with AD consuming KD, MCTs, and/or ketone ester also report cognitive improvement (Maynard Neuropsych Disease Treat 2013; Newport Alz Dementia 2015; Stoykovich Alz Dementia 2019; Morrill Diab Metab Syndr:Clin Res & Rev 2019). Ketone esters can rapidly and substantially increase blood ketone levels. Given the lack of any FDA‐approved drug that results in meaningful improvement for people with AD, accumulating evidence suggests that adopting a personalized program for people with AD, aiming for mild to moderate ketosis (blood betahydroxybutyrate levels 0.5‐2 mmol/L), could provide a safe and reasonable therapeutic approach to improve cognitive impairment and other symptoms and could offer a strategy to delay or prevent AD in persons at risk.

Falls and Cognition in Adults Aging with Down Syndrome

AbstractBackgroundAdults with Down syndrome (DS), who are at risk, will show the neuropathological changes of Alzheimer’s Disease (AD) within their 40s, partially due to an overexpression of beta‐amyloid, which accumulates in the brain across their lifespan. The risk of developing AD in adults aging with DS increases with age and is marked by increased confusion, short‐term memory problems, and/or a loss of the ability to complete daily activities. There is limited evidence on the functional changes that happen to adults aging with DS prior to any marked AD symptoms. Growing evidence suggests that functional mobility abnormalities and an increase in falls may precede cognitive impairment and marked AD symptoms. The relationship between falls and cognition in adults with DS has not been thoroughly investigated; and could potentially serve as a less invasive method of assessment.MethodThe purpose of this study is to assess patterns of falls and functional mobility impairments that occur within an adult population aging with DS and their relationship with cognition. The participant receives an initial home visit, conducted by the PI, who completes and collects data on functional performance, fall risk(s), and the environment. The participant agrees to document any fall incidents using a calendar journal, and completes the monthly check‐in calls and/or emails initiated by the study team.ResultWe conducted a correlation analysis with the preliminary data from this cohort of 17 participants, 9 male and 8 female, with a mean age of 38.5 years (SD = 8.81). Increased falls were significantly related (p < .05) to impaired gait speed (r = .528) and balance (r = ‐.624), while cognition (r = .474, p >.05) was not associated with falls. Increased fear of falling assessment scores were correlated with impaired gait speed (r = .687), lower extremity (r = ‐.502) and mean grip strength (r = ‐.492), and balance (r = ‐.596).ConclusionWe demonstrated that (1) participants were willing to enroll; (2) the assessment and monitoring plan were well tolerated; and (3) fear of falling scores and decreased functional mobility were similar in aging adult with DS populations to older adult (≥ 65 years of age) populations.

A population‐based investigation of brain changes related to Alzheimer’s disease in middle‐aged adults in Brazil

AbstractBackgroundGiven the progressive nature of neurodegenerative pathologies, great effort has been made to create diagnostic tools for detecting neurodegenerative changes in their early stages. However, the lack of information about the frequency of neurodegenerative changes in mid‐age adults impacts biomarker interpretation and sensitivity improvement. In addition, recent clinicopathological studies have shown than even a low Alzheimer’s disease (AD) neuropathological burden can significantly impact neuropsychiatric function. Finally, clinicopathological studies point to a role of small cerebrovascular changes in the cognitive decline of individuals with zero or low neurodegenerative burden; however, it remains unclear if small vascular brain lesions can impact cognition in younger mid‐age individuals.MethodWe evaluated the presence of AD neuropathological changes and their relationship with cognitive impairment, neuropsychiatric symptoms and risk factors in a multiethnic and heterogeneous group under 65 years of age at the moment of death, most of them with low educational level (Table 1). A semi‐structured interview with an informant was performed to obtain socioeconomic and clinical data. Internationally accepted neuropathological criteria were used for pathologic diagnosis.ResultSome degree of neurofibrillary pathology was found in 53% (n = 145) of the individuals, while neuritic plaques were found in 10% (n = 26) of the cases, regardless of the presence of cognitive impairment or neuropsychiatric symptoms. AD‐type pathology burden was similar among individuals with and without cognitive impairment. However, a higher frequency of vascular pathology (p<0.001) was found in individuals with cognitive impairment (Table 2). Some degree of neuropsychiatric symptoms was noted in 59% (n = 160) of the cases. High frequency of cerebrovascular risk factors such as hypertension (63.9%), smoking (58.5%) and alcohol intake (27.5%) was also observed in the entire sample (n = 275) (Table 1).ConclusionOur data shows that AD neuropathological changes can begin in mid‐age and corroborates findings from other series with predominantly older Caucasians of high scholarity that have demonstrated the role of vascular pathology in cognitive impairment. As vascular risks are preventable, aggressive measures to reduce these factors may impact the prevalence of cognition‐related dysfunction.

Impact of loneliness and social isolation in older people in Japan

A decline in social functioning is a hallmark of dementia and is associated with worsening cognitive impairment, various behavioral and psychological symptoms, and caregiver burden. Since the feeling of loneliness is related to social function decline in people with mild cognitive impairment (MCI) and dementia, care for the social isolation that can cause loneliness is considered important in Japan, where the number of older people living alone is increasing.In addition to dementia, late-onset psychosis is also known to be affected by loneliness and social isolation. Psychosis that develops after age 60 and does not involve organic or affective disorders is defined as very late-onset schizophrenia-like psychosis (VLOSLP) and is known to be different in quality from psychosis that develops at a younger age. Social isolation has been reported as one of risk factors of VLOSLP, and although people with VLOSLP are independent in daily life, their social functioning is impaired in a way that is different from dementia due to their abnormalities in the content of thinking. Therefore, social isolation and decline of social functioning are also major problems for VLOSLP. Longitudinally, people with VLOSLP are more likely than the general older population to progress to dementia including Lewy body disease and Alzheimer’s disease subtypes. With the increasing importance of early diagnosis and intervention of these neurodegenerative diseases, identification and intervention of people with VLOSLP is a challenging but important topic.We are now investigating the use of robots with communication capabilities aiming to improve loneliness and social isolation of older people living alone with MCI, mild dementia and VLOSLP. On the other hand, we have found that loneliness in MCI and mild dementia does not necessarily correlate with social isolation status, such as living alone, indicating that loneliness and social isolation among older people requires further research.

Rhythmic Musical Intervention Improves Short‐term Memory Function in Healthy Elderly: A Prospective Pilot Study of a Group‐based African Drum Training

AbstractBackgroundMemory complaints are the early symptoms of cognitive impairment, and it usually brings anxiety about cognitive deterioration among the elderly population. Musical interventions were demonstrated to relieve dementia symptoms1. This study is to investigate the potential benefits of African drum intervention on cognitive functions.MethodParticipants were recruited in July 2022 through social media advertisement. Classes were organized in a drumming activity center in downtown, Kowloon. Participants joined 8 sessions of African drum training which covered rhythmic clapping and drumming, power control, and overall performance with songs. The inclusion criteria were participants (1) aged over 50 years old and (2) able to use a smartphone. Participants who could not understand Chinese or had been diagnosed with active psychosis or dementia were excluded. Cognitive function was screened by an online platform, ScreenMat2, for short‐term and long‐term memory, orientation, calculation, visual function, and followed up with the Hong Kong version of the Montreal Cognitive Assessment (HK‐MoCA). Anxiety and depression levels were assessed by State‐Trait Anxiety Inventory (STAI) and Geriatric Depression Scale (GDS). All assessments were performed before and after the drumming classes (Figure 1). The outcomes were evaluated using Wilcoxon Signed Rank Test with 0.05 as the significance level.ResultTwenty‐four participants joined this study with an attendance rate of 83%. The overall cognitive function of the participants was good with an average score of 27 for HK‐MoCA. After 8 sessions of African drum intervention, the cognitive function did not show significant improvement (p = 0.108), but the response time of answering the digital cognitive questions was significantly faster than that before the intervention (‐39.9 seconds, p = 0.03) (Table 1). The response time for the short‐term memory function was the most significantly reduced better after the African drum training (‐13.5 seconds, p = 0.005) The STAI and GDS scores also significantly decreased (p<0.001).ConclusionRhythmic Musical Intervention, such as the African drum, can improve the response time of cognitive tests and also relieve anxiety and depression levels.1. Tsoi et al. J Am Med Dir Assoc. 2018;19(7), 568‐576. https://doi.org/10.1016/j.jamda.2017.12.0092. Lam et al. In Proceedings of the 51st HICSS. 2018. doi:10.24251/HICSS.2018.353

Edukasi Mengenai Gangguan Kognitif Pada Pasien Hipertensi di Poli Neurologi Rumah Sakit Universitas Mataram

Cognitive impairment in hypertensive patients is a significant clinical problem. It is a prevalent condition that has a major impact on quality of life. Hypertension, characterized by persistently elevated blood pressure, has been identified as a potential risk factor for cognitive impairment. Assessing cognitive function in hypertensive patients is essential for early detection and intervention. Community participation is crucial to raise awareness about the symptoms of cognitive impairment in hypertensive patients. Therefore, education on cognitive impairment associated with hypertension is necessary to reduce its morbidity. This community service activity aims to provide education on the definition, signs, and symptoms, as well as early detection methods of cognitive impairment in hypertensive patients to patients and their families at the neurology clinic University of Mataram Hospital. The activity was conducted using an interactive method with the aid of PowerPoint slides. The participants were given a pre-test, followed by a presentation on the disease, a discussion session, and finally, a post-test. There were 14 participants in total. The education session began with a pre-test consisting of five questions about cognitive impairment and hypertension. The participants' average score was 74.2. The material covered definitions, symptoms, early signs, and how to conduct early detection of cognitive impairment and hypertension. The education session concluded with a post-test, which revealed that 10 participants (71.4%) showed an increase in their knowledge scores, with a mean score of 88.5. Effective communication, information, and education are essential in improving knowledge about the early detection of cognitive impairment in hypertensive patients.

Protection of p-Coumaric acid against chronic stress-induced neurobehavioral deficits in mice via activating the PKA-CREB-BDNF pathway

There is a body of evidence to suggest that chronic stress modulates neurochemical homeostasis, alters neuronal structure, inhibits neurogenesis and contributes to development of mental disorders. Chronic stress-associated mental disorders present common symptoms of cognitive impairment and depression with complex disease mechanisms. P-coumaric acid (p-CA), a natural phenolic compound, is widely distributed in vegetables, cereals and fruits. p-CA exhibits a wide range of health-related effects, including anti-oxidative-stress, anti-mutagenesis, anti-inflammation and anti-cancer activities. The current study aims to evaluate the therapeutic potential of p-CA against stress-associated mental disorders. We assessed the effect of p-CA on cognitive deficits and depression-like behavior in mice exposed to chronic restraint stress (CRS); we used network pharmacology, biochemical and molecular biological approaches to elucidate the underlying molecular mechanisms. CRS exposure caused memory impairments and depression-like behavior in mice; p-CA administration attenuated these CRS-induced memory deficits and depression-like behavior. Network pharmacology analysis demonstrated that p-CA was possibly involved in multiple targets and a variety of signaling pathways. Among them, the protein kinase A (PKA) - cAMP-response element binding protein (CREB) - brain derived neurotrophic factor (BDNF) signaling pathway was predominant and further characterized. The levels of PKA, phosphorylated CREB (pCREB) and BDNF were significantly lowered in the hippocampus of CRS mice, suggesting disruption of the PKA-CREB-BDNF signaling pathway; p-CA treatment restored the signaling pathway. Furthermore, CRS upregulated expression of proinflammatory cytokines in hippocampus, while p-CA reversed the CRS-induced effects. Our findings suggest that p-CA will offer therapeutic benefit to patients with stress-associated mental disorders.

Abstract 18912: Interplay Between Cognitive Function and Depressive Symptoms in Patients With Heart Failure

Introduction: Mild cognitive impairment (MCI) and depressive symptoms (DS) are common comorbidities in patients with heart failure (HF). MCI and DS are known to be related from cross-sectional studies, but the trajectory of DS over time is unknown in patients with HF and MCI. Objective: To compare the trajectory of DS over a 2-year period based on cognitive function in patients with HF. Methods: We studied 373 patients (age 65 ± 13 years, 60% male, 26% NYHA class III/IV) with HF for 24-months. MCI was assessed using the Mini-Cog Test, and DS using the Patient Health Questionnaire-9; MCI was measured at baseline, and DS at baseline, 12 and 24 months. We used repeated-measures ANOVA for analysis with age and New York Heart Association (NYHA) class as covariates. Results: There was a significant time by group interaction (p = 0.027) in that DS decreased across time from baseline to 24-months in patients without MCI, while DS in patients with MCI, although decreased at 12-months, returned to baseline levels at 24-months (Figure). Although DS were higher in patients with worse NYHA class, they showed the same trajectory across time based on MCI. Conclusions: Although these data suggest that MCI worsens or prevents remission of DS overtime, the interplay between these two conditions requires further study to better understand how MCI and DS affect each other and how they interact to alter outcomes in patients with HF.

Mitochondrial protein prohibitin promotes learning memory recovery in mice following intracerebral hemorrhage via CAMKII/CRMP signaling pathway

Prohibitin (PHB) is a mitochondrial inner membrane protein with neuroprotective, antioxidant, and apoptosis-reducing effects. This study aimed to explore the role of PHB in pathological symptoms, behavioral deficits, and cognitive impairment in a collagenase-IV-induced intracerebral hemorrhage (ICH) murine model. In this study, mice that received collagenase IV injection were pretreated with PHB or saline 21 days prior to modeling. The role of PHB in memory and learning ability was monitored using the Morris water maze, Y-maze, and rotarod, social, startle, and nest-building tests. The effect of PHB on depression-like symptoms was examined using the forced swimming, tail suspension, and sucrose preference tests. Subsequently, mouse samples were analyzed using immunohistochemistry, western blotting, Perls staining, Nissl staining, and gene sequencing. Results showed that collagenase IV significantly induced behavioral deficits, brain edema, cognitive impairment, and depressive symptoms. PHB overexpression effectively alleviated memory, learning, and motor deficits in mice with ICH. PHB markedly inhibited the number of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling-positive cells and protein levels of ionized calcium-binding adapter molecule 1, glial fibrillary acidic protein, and interleukin-1β in the perihematomal region of ICH mice. PHB overexpression also remarkably promoted production of neurologin1 (NLGL1), and upregulated levels of Ca2+-calmodulin-dependent kinase II (CaMKII) and collapsin response mediator protein-1 (CRMP1) proteins. In conclusion, PHB overexpression can effectively alleviate the neurological deficits and neurodegeneration around the hematoma region. This may play a protective role by upregulating the expression of NLGL1 and promoting expression of CaMKII and CRMP1.

HIV-1 gp120-Induced Cognitive Disorder Is Concomitant with Altered Gut Microbiota

Background HIV-associated neurocognitive disorders (HAND) is an essential factor affecting the quality of life of people living with HIV (PLWH), and the prevalence of HAND in PLWH can reach 19% to 64%. More than 50% of HAND patients treated with highly active antiretroviral therapy (HAART) did not show improvement in symptoms of cognitive impairment. HIV-1 envelope protein gp120 may be a major contributor to HAND pathology. HIV-1 gp120 enters neurons by binding CXCR4 and CCR5 and can also bind neuronal tubulin to cause direct neurotoxicity and neuronal death. HIV-1 gp120 transgenic mice (Tgm) are commonly used as HAND animal models, and Tgm brain pathological changes and differential gene expression are highly consistent with HAND patients. Intestinal flora affects the progression of diseases by regulatory the intestinal barrier, and several studies have confirmed that the normalization of abnormal intestinal flora reduces the damage to the nervous system in a variety of neurodegenerative diseases. Studies reported that Akkermansia muciniphila has a downward trend in PLWH, which may cause intestinal barrier damage. There is still a lack of relevant evidence to confirm the association between abnormal changes in gut microbiota and HAND induced by HIV-1 gp120. Therefore, in this study, we examined the gut microbiota changes in 6, 9, and 12 months Tgm to explore the relationship between age-dependent significantly different bacterial genera, intestinal barrier and neuronal damage. Methods The fresh feces were collected from HIV-1 gp120 transgenic mice (Tgm) and C57BL/6J mice (wild type, WT) at ages 6, 9, and 12 months using perianal stimulation at the same time (n=5). Total bacterial DNA was extracted from each fecal sample and the V3-V4 region of 16S rRNA was sequenced by the Illumina MiSeq platform. 12 months Tg and WT mice were sacrificed, and serum was collected to detect lipopolysaccharide (LPS) concentration by ELISA, and brain tissue of mice in each group was collected for Map2 immunohistochemical staining (n=5). SPSS 20.0 software was used for statistical analysis. P <0.05 were considered statistically significant. Results 16S rRNA analysis showed that increased age was significantly associated with increased abundance of Blautia ( P <0.01) and Prevotellaceae_NK3B31_group ( P <0.0001) genus and decreased abundance of Akkermansia genus ( P <0.05) in Tgm. Notably, the increasing age of WT was associated with the opposite trend of Blautia, Prevotellaceae_NK3B31_group and Akkermansia genus abundance, indicating those genus changes with age and gp120 induced. To further explore the effect of gut microbiota on the gut barrier, serum LPS concentrations were detected for 12 months Tgm and WT. The results showed that serum LPS level was significantly higher in Tgm than in WT ( P <0.01), indicating that the intestinal barrier may be impaired in Tgm. Finally, we collected 12 months Tgm and WT brain tissues for Map2 immunohistochemical staining to evaluate neuronal synaptic length and integrity. Compared with WT, the expression of map2 in the hippocampus and cerebral cortex was significantly decreased ( P <0.05), indicating neuronal damage in Tgm. Conclusion At the genus level, the abundance of Akkermansia was negatively correlated and the Blautia and Prevotellaceae_NK3B31_group abundance was positively correlated with increasing age in Tgm but showed an opposite trend in WT. The serum LPS level increased dramatically in the 12 months Tgm, indicating Tgm with intestinal barrier damage. Map2 expression was reduced considerably hippocampus and cortex in Tgm brain, which means neuronal synaptic integrity was impaired. ( Acknowledgements: National Natural Science Foundation of China, No. 82172259 to H.C.; Corresponding author: Hong Cao, gzhcao@smu.edu.cn.)