Severe Cognitive Impairment Research Articles

Presence and Characteristics of Behavioral and Psychological Symptoms in Subacute Stroke Patients with Cognitive Impairment.

This retrospective cross-sectional study is aimed at investigating the prevalence and characteristics of behavioral and psychological symptoms (BPS) in subacute stroke patients with cognitive impairment. The Neuropsychiatric Inventory-Questionnaire (NPI-Q) was used to assess BPS. A total of 358 consecutive patients with first-ever stroke admitted to rehabilitation wards and with Mini-Mental State Examination (MMSE) scores < 24 on admission were included. BPS was defined as a total NPI-Q Severity or Distress score ≥ 1. Differences between the severity and presence of BPS among patients with severe cognitive impairment (MMSE scores 0-17) and those with mild cognitive impairment (MMSE scores 18-23) were analyzed using the Mann-Whitney U test and chi-squared test, respectively. Eighty-one patients (mean (standard deviation) age, 73.5 (13.1) years) were enrolled for analysis. BPS were observed in 69.1% and 74.1% of patients when assessed with NPI-Q Severity and NPI-Q Distress, respectively. The most frequently observed BPS was apathy, followed by depression (approximately 44% and 40%, respectively). The severity and frequency of delusions, euphoria, apathy, and disinhibition were significantly higher in the severe cognitive impairment group than in the mild cognitive impairment group. However, the severity, distress, and frequency of depression were not dependent on the severity of cognitive impairment. The presence of BPS, especially apathy and depression, in subacute stroke patients with cognitive impairment is high. The severity and frequency of some BPS are higher in patients with severe cognitive impairment than in those with mild cognitive impairment. However, depression is highly prevalent among the patients regardless of the severity of cognitive impairment.

Association of Sleep Status With Cognitive Functions in Centenarians: Evidence From Hainan Centenarian Cohort.

This study aimed to analyze the association between sleep quality, sleep duration, and cognitive functions among centenarians. The baseline data of the China Hainan Centenarians Cohort Study served as the foundation for this study. Logistic regression was utilized to demonstrate the relationship between sleep status and cognitive impairment. Moreover, a canonical correlation analysis was performed to analyze the correlation between these variables. A total of 994 centenarians were included. After adjustment, poor sleep quality centenarians had an odds ratio of 1.77 (95% confidence interval [CI]: 1.00-3.09) for cognitive impairment when compared to centenarians with normal sleep quality. Centenarians who slept for more than 9hr had a stronger association with severe cognitive impairment, indicated by an odds ratio of 1.41 (95% CI: 1.02-1.96), compared to those who slept for 7-9hr. Additionally, the canonical correlation analysis results revealed that the linear combination of sleep quality V1, primarily determined by sleep latency, daytime dysfunction, and subjective sleep quality, was associated with cognitive function; the linear combination of cognitive function W1, mainly determined by orientation, attention and calculation, and memory. There exists a correlation between poor sleep quality and cognitive impairment in centenarians, as well as a correlation between sleep duration >9hr at night and severe cognitive impairment. The primary cognitive domains associated with sleep quality are orientation, calculation, and memory. It is imperative to monitor and safeguard the cognitive functions linked to poor sleep quality in the older individuals, with attention to orientation, calculation, and memory.

Epilepsy and MELAS syndrome: literature review and clinical observation

MELAS syndrome (mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes) belongs to the group of mitochondrial diseases. Most MELAS syndrome cases are associated with the A3243G mutation in the MTTL1 gene. A common clinical manifestation of the syndrome is presented by epileptic seizures (ES) characterized by phenotypic polymorphism and resistance to antiepileptic therapy. Diagnosis and treatment of epilepsy in patients with MELAS syndrome often poses difficulties. We present a clinical case of adult patient with MELAS syndrome with identified A3243G mutation and epilepsy. The disease course developed to severe cognitive impairment. The first focal ES occurred during stroke-like episode. Further seizures were observed spontaneously, with high frequency, often manifested as a series. Focal ES often had blurred polymorphic manifestations. The choice of drug therapy took into account the side effects of antiepileptic drugs (AEDs) including potentially mitochondria-related negative effects. While diagnosing EP in MELAS syndrome, it should be considered that seizures often occur during stroke-like episodes and may have blurred polymorphic clinical manifestations. Cognitive impairment in patients complicates ES detection. First-line drugs should be presented by AEDs with low mitochondrial toxicity.

ETHICAL CONSIDERATIONS UNDERLYING ACP FOR ACCOMPANIED OLDER ADULTS WITH COGNITIVE IMPAIRMENT

Abstract While clinicians understand the importance of ACP, it is difficult to overcome logistical and ethical challenges in the limited time providers have in primary clinic appointments with older adults with ADRD and other complex co-morbidities. Ethical/moral dilemmas faced by patients, families, and clinicians are reflected in the four principles of biomedical ethics including autonomy, beneficence, nonmaleficence, and justice. While ethical challenges are recognized there is a lack of real-world evidence to guide clinicians or family caregivers in ACP for older adults with ADRD based on the reality of complex patient and family dynamics. Throughout the SHARE trial, facilitated ACP conversations with trained ACP facilitators, older adult patients with cognitive impairment, and their family caregiver were audio recorded and transcribed. The purpose of this presentation is to expand our understanding of best practices for facilitating ACP conversations among persons with ADRD and their family caregivers, guided by medical ethics and the Learning Health Care System Ethics Framework. We draw on the unique dataset of recorded ACP conversations involving older adults with severe cognitive impairment (N=92, average age=88 years), family caregivers, and trained ACP facilitators. We qualitatively coded transcripts for ethical considerations of ACP conversations and conducted the thematic analysis. We will present major themes related to ethical considerations in facilitating ACP conversations among persons with moderate to severe ADRD and their family caregivers. We will provide a discussion framed in balancing patient, family, and provider needs within a Learning Health Care System.

PRIMARY OUTCOMES FROM CAREGIVER-REPORTED SURVEYS IN THE SHARE TRIAL

Abstract This presentation will introduce SHARE, a randomized-controlled trial to proactively engage family caregivers and normalize advance care planning in primary care. The objective of the study is to engage family caregivers in longitudinal interactions with primary care clinicians and stimulate and support ACP discussions in primary care. We focus on persons with mild, moderate, and severe cognitive impairment regardless of clinical diagnosis because of the importance of addressing advance care planning early in the disease trajectory, the under-diagnosis of ADRD, and because of the greater implementation potential of a protocol with broader applicability. We will describe the study design and present on 6-month outcomes to test our hypothesis that as compared with the minimally enhanced control care group, caregivers in the intervention group will report better quality of communication about end-of-life care with primary care clinicians at 6 months (primary outcome).

THE FEASIBILITY OF TAICHI WITH MUSIC FOR HEALTH IN INDIVIDUALS LIVING WITH ADRD AND THEIR CAREGIVERS

Abstract Caregiving demands associated with cognitive and physical function decline in care recipients (CRs) living with Alzheimer’s disease and related dementias (ADRD) contribute to compromised health and quality of life among ADRD caregivers. In turn, the affected health of caregivers affects the care quality of CR and their health. TaiChi or music is evidenced to be beneficial for the generation population and those with various health conditions. This pilot project assessed the feasibility and preliminary efficacy of an 8-week TaiChi with music (TCM) program on individuals with ADRD (e.g., physical and cognitive function) and their family caregivers (e.g., caregiver distress and quality of life). Outcomes were compared between baseline and post-intervention using paired t-tests. Qualitative interview data exploring the perceptions of participating in TCM program were analyzed using content analysis. Five dyads were enrolled in this study (CR age=77.4±6.8; Caregiver age=62.6±6.7). The overall class attendance rate is 65%. Among the small but diverse sample, adult child care dyads had higher class attendance (93%); spousal care and CR with severe cognitive impairment dyads had lower attendance (46%). Improvements were found in assessed health outcomes for both CR and caregivers, and CR’s physical function significantly improved at 8-week (p=0.016). Qualitative data revealed perceived balance improvements; Caregivers perceived calmness and peace, and expressed their interest in participating in TCM in the future. TCM may be more feasible in ADRD individuals with mild to moderate cognitive impairment. Future research will evaluate the efficacy of this intervention in a larger sample with a longer follow-up period.

GWAS OF BRAIN ENDOPHENOTYPES: ASSOCIATION OF AUTOPSY-BASED LEWY BODY COUNTS WITH MOVEMENT DISORDER RISK LOCI

Abstract We performed a genome wide association study (GWAS) of neocortical Lewy body density. Case material were 308 autopsies of Japanese-American men (mean age at death 87.5 years; 11% with mild, and 30% with severe cognitive impairment prior to death). Lewy bodies were assessed by manual count of alpha-synuclein stained neocortical sections from the frontal, temporal, parietal, and occipital lobes. Genetic association was tested by linear models controlling for age at death assuming an additive genotypic effect. Top hits include a locus on chromosome 1q32 previously associated with amyotrophic lateral sclerosis (p=5.8e-8), intronic variants on the dopaminergic neuron axonal guidance gene EPHB1 previously associated with Parkinson’s disease (PD) (p=8.4e-6), and a locus containing two independent intron 1 variants on CSMD1, a known risk factor for autosomal dominant PD (p=1.5e-6). Complement inhibitor protein CSMD1 is a type 1 transmembrane cell adhesion molecule implicated in axonal guidance and the development, maintenance, and pruning of synapses in the adult brain. Intermediate hits include genes encoding cell adhesion molecules and a second complement inhibitor implicated in the regulation of synapses (TRAPPC9). This converging evidence points to cell adhesion proteins and complement mediated synaptic regulation in the etiology of Lewy body lesions.

ASSOCIATIONS OF NIGHT AND DAY SLEEP WITH COGNITIVE PERFORMANCE IN SHIFT WORKERS: PRELIMINARY RESULTS

Abstract Emerging evidence suggests that night shift workers are at higher risk of severe cognitive impairment, mainly because of the repeated disruption of the sleep–wake schedule and the resulting poor sleep (e.g., less deep sleep or shorter sleep time). However, questions remain about how daytime and nighttime sleep characteristics correlate with cognitive performance in shift workers. The purpose of this study is to examine the association of objective sleep quality, measured on workdays and days off, with cognitive performance, determined by the psychomotor vigilance task (PVT), in shift workers compared to day workers. We included eight night shift and ten day shift workers from an ongoing pilot study in this analysis. Participants undergo multiple home sleep studies with electroencephalograms on their workdays or days off. Sleep quality measures include total sleep time (TST), percentage of deep sleep stage in TST, and wake time after sleep onset (WASO). Night shift workers showed longer TST and shorter WASO during their nighttime sleep on days off compared to day shift workers. In night shift workers, longer deep sleep on days off was significantly correlated with faster mean reaction time to a visual stimulus (better cognitive performance) on the PVT (r = -.944, p = .016), after controlling for age. However, longer deep sleep during their daytime sleep was associated with slower reaction time (r = .756, p = .049). Further studies are necessary to elucidate differential impacts of daytime and nighttime sleep on the risk of future cognitive impairment in night shift workers.

Kidney function and other associated factors of sarcopenia in community-dwelling older adults: The SCOPE study

AimSarcopenia is associated with several factors and medical conditions among older adults, though previous research has shown limitations and inconsistencies, especially regarding chronic kidney disease (CKD). We investigated the clinical and laboratory variables associated with sarcopenia and severe sarcopenia in older adults, focusing on kidney function measures. MethodsData from community-dwelling adults aged ≥75 years participating in the SCOPE multicenter prospective cohort study were assessed cross-sectionally. Comprehensive geriatric assessment was conducted; sociodemographic and lifestyle factors, clinical variables and comorbidities, anthropometric and bioelectrical impedance analysis, blood and urine laboratory variables were collected. EWGSOP2 revised criteria were used to define sarcopenia and its severity. Estimated glomerular filtration rate (eGFR) was calculated using creatinine and non-creatinine-based equations, and CKD stages were defined accordingly. Results1420 participants were included, prevalence of sarcopenia was 10.6 %, and 6 % had severe sarcopenia. Multivariate logistic regression analysis showed that age [OR =1.14; 95 %CI (1.09–1.19)], body mass index (BMI) [0.83 (0.79–0.88)], disability performing instrumental activities of daily living (IADL) [2.61 (1.69–4.06)], Mini Mental State Examination (MMSE) score <24 [2.75 (1.62–4.67)], osteoporosis [2.39 (1.55–3.67)], and stage 4 CKD defined by CKD-EPIBTP-B2M, a non-creatinine-based eGFR equation [2.88 (1.11–7.49)], were independently associated with sarcopenia; as were specifically with severe sarcopenia, with more pronounced associations. ConclusionsIn community-dwelling older adults, sarcopenia is a relevant condition and is associated with severe CKD, older age, IADL, cognitive impairments, osteoporosis and low BMI. These factors should be assessed for proper identification and management of older patients with sarcopenia, and even more so with severe sarcopenia.

Worsening of cerebral palsy following neonatal encephalopathy: A meta-analysis

Cerebral palsy (CP), the most common motor disorder in early childhood, arises from neonatal brain injury. The potential role of neonatal encephalopathy (NE) as a risk factor for cerebral palsy has been postulated, yet a systematic examination of its clinical impact on cerebral palsy patients remains absent. This meta-analysis aims to delineate the incidence of commonly reported complications associated with cerebral palsy following NE compared to those without a history of NE. A systematic search of PubMed and Google Scholar yielded 424 studies, with 7 meeting the inclusion criteria. These studies reported at least one comparison of cerebral palsy symptoms between patients with or without NE and provided the corresponding case numbers for each group. Utilizing RevMan 5.4, we analyzed the data and assessed potential publication bias. Among the 7 studies included, we compared the characteristics of 117 patients with cerebral palsy with preceding NE to 287 without such antecedents. Significantly, the incidence of the spastic quadriplegic subtype of cerebral palsy was higher in patients with NE (odds ratio [OR]: 4.34, 95% confidence interval [CI]: 2.69 &amp;ndash; 7.00, P &lt; 0.00001). CP patients following NE exhibited a significantly increased incidence of severe communication difficulties (OR: 2.33, 95% CI: 1.32 &amp;ndash; 4.10, P = 0.003), difficulty swallowing (OR: 2.50, 95% CI: 1.31 &amp;ndash; 4.77, P = 0.005), and cognitive impairment (OR: 2.73, 95% CI: 1.45 &amp;ndash; 5.13, P = 0.002). Children with cerebral palsy born following NE were more predisposed to the most severe spastic quadriplegic subtype and encountered significant comorbidities. It is essential to acknowledge the limitations of this study, primarily the small number of studies that separately reported cerebral palsy cases with or without NE. Nevertheless, these findings contribute valuable insights for a more accurate clinical prognosis and the prospective development of targeted treatments for specific complications associated with cerebral palsy in patients with NE.

Combinatorial Treatment by NPD1 Plus RvD1 Elicits Neurobehavioral Recovery and Increases Homeostatic Gene Expression after Experimental Ischemic Stroke

Stroke is the second leading cause of death worldwide and a high proportion of those who survive stroke develop severe cognitive impairments. Current therapies, tissue plasminogen activator (tPA) and thrombectomy, are ineffective for most patients affected by stroke. This research explores mechanisms and examines the potential of combined Neuroprotectin D1 (NPD1) and Resolvin D1 (RvD1) treatment in ischemic stroke.

Overview of Diabetes as a Risk Factor for Developing Dementia: A Systematic Review

Background: There is debate over the relationship between diabetes and the main forms of dementia. The cognitive alterations associated with type 2 diabetes (T2D) mostly impact mental flexibility, mental speed, and learning and memory.&#x0D; Objectives: To ascertain the degree of the link between diabetes and dementia, we thoroughly reviewed papers on the incidence of dementia in individuals with diabetes mellitus in this study.&#x0D; Methods: PubMed, SCOPUS, Web of Science, and Science Direct were systematically searched for relevant literature. Rayyan QRCI was employed throughout this comprehensive process.&#x0D; Results and Interpretation: We included ten studies with a total of 173797 participants, and 78828 (45.4%) were males. All of the included studies were prospective cohorts. For diabetic patients, early-onset diabetes, poor glycemic management, and diabetes status are risk factors for dementia development. There was also a higher chance of dementia development in those with mild to severe motor cognitive impairment and hereditary variables. Longitudinal studies that involve comprehensive evaluations of comorbid diseases and diabetes-related variables, as well as rigorous assessments of cognition—ideally in conjunction with neuroimaging—will be necessary for this process. This method will work best with large population-based cohort studies of older adults with diabetes and with longitudinal studies of at-risk groups that look at the development of diabetes, metabolic syndrome, vascular disease, and cognitive decline.

Network analysis of illness perception, stigma, and resilience with cognition in old people living with HIV

ObjectivesOld people living with HIV (PLWH) are highly susceptible to HIV-related psychological and neurocognitive disorders, which are multidimensional and inseparably intertwined. Despite this, few studies have investigated the interrelationship between these disorders. We aimed to estimate the detailed associations and identify potential intervention points between HIV-related psychological factors and cognitive function in old PLWH. MethodsThis cross-sectional study drew on the Older People with HIV Infections Cohort from 65 communities in Sichuan, China. Three HIV-related psychological factors, including illness perception, HIV stigma perception and resilience, were collected using a self-reported questionnaire. Cognitive function was measured using the MoCA-B scale. Network analysis was used to estimate the interrelationships between HIV-related psychological factors and cognitive function dimensions in old PLWH, and to identify factors that act as bridges in connecting these factors in the network. ResultsOf the 1587 old PLWH, 47.0% had mild or severe cognitive function impairment. Network analysis revealed that better visual perception was directly connected with poorer negative self-image (edge weight: 0.13), and poorer illness comprehensibility was connected with poor visual perception (−0.09) and executive functioning (−0.13). The cognitive illness perceptions (bridge strength: 0.41), illness comprehensibility (0.36) and negative self-image (0.39) were identified as bridges connecting HIV-related psychological and cognitive function. ConclusionsThe interconnection of HIV-related illness perception, stigma perception, and resilience with cognition may be achieved through the links of negative self-image, illness comprehensibility and cognitive illness perceptions. These factors may serve as potential non-pharmaceutical action points to improve psychological and cognitive health among old PLWH.

Physical function decline predictors in nursing home residents using new national quality indicators.

To determine the predictors of physical function (PF) decline among nursing home residents using items from the Long-term care Information system For Evidence (LIFE), a system launched in 2021 to ensure the quality of long-term care. The LIFE data of 1648 residents from 45 nursing homes in Japan were retrospectively collected in July 2021 (T0) and January 2022 (T1), including demographics, PF assessed by the Barthel index (BI), nutrition and oral health, and cognitive function. The Dementia Behavior Disturbance scale was used to assess the frequency of certain behaviors, such as "waking at midnight." The predictors of PF decline, defined as a decrease ≥5 in the BI score at T1 compared with that at T0, were determined using mixed-effects logistic regression analyses. PF at T0 was classified into high (>60 BI) and low (≤60 BI) groups. The participants' mean age was 87.2 ± 7.1 years, and 45.3% experienced PF decline. The significant predictors of PF decline were age ≥ 90 years, body mass index <18.5 kg/m2 , dementia diagnosis, moderate and severe cognitive impairments, not vocalizing reciprocal exchanges at will, always "waking at midnight," and high PF at T0. The LIFE items predicted PF decline among nursing home residents, suggesting that LIFE data can be used to ensure the quality of long-term care. Geriatr Gerontol Int 2024; 24: 123-132.

Evaluating the heterogeneity of hippocampal avoidant whole brain radiotherapy treatment effect: A secondary analysis of NRG CC001.

Hippocampal avoidant whole brain radiotherapy (HA-WBRT) is the standard of care for patients needing WBRT for brain metastases. This study, using existing data from NRG Oncology CC001 including baseline tumor characteristics and patient-reported MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT) scores, sought to identify subgroups of patients that demonstrate differential neuroprotective treatment response to HA-WBRT. An exploratory analysis of NRG CC001, a phase 3 trial in which 518 patients were randomly assigned to WBRT plus memantine or HA-WBRT plus memantine, was performed. Rates of neurocognitive function failure (NCFF) were estimated between subgroups and stratified by arm. Covariate and subgroup interaction with differential treatment response were calculated. The benefit of HA-WBRT on decreasing NCFF was seen in patients living ≥ 4 months (HR 0.75, 95% CI: 0.58-0.97, P = .03), whereas patients living < 4 months derived no significant neurocognitive benefit. A significant association between baseline MDASI-BT cognitive factor and treatment response (interaction P = .03) was identified. Patients with lower MDASI-BT scores (less patient-reported cognitive impairment) derived significantly greater benefit (HR = 0.64, 95% CI: 0.48-0.85, P = .002) compared to those with highest MDASI-BT scores (HR = 1.24, 95% CI: 0.76-2.04, P = .39). Tumor histology also had a significant interaction (P = .01) with treatment response. Primary lung histology patients derived cognitive failure risk reduction (HR = 0.58, 95% CI: 0.43-0.77, P = .0007) from HA-WBRT, in contrast to nonlung primary histology patients (HR = 1.15, 95% CI: 0.78-1.50, P = .48). Differential neuroprotective response to HA-WBRT was identified in this analysis. Patients surviving ≥ 4 months derived benefit from HA-WBRT. There is evidence of heterogeneity of treatment effect for patients with less severe patient-reported cognitive impairment at baseline and those with primary lung histology.

Local production of reactive oxygen species drives vincristine-induced axon degeneration

Neurological side effects arising from chemotherapy, such as severe pain and cognitive impairment, are a major concern for cancer patients. These major side effects can lead to reduction or termination of chemotherapy medication in patients, negatively impacting their prognoses. With cancer survival rates improving dramatically, addressing side effects of cancer treatment has become pressing. Here, we use iPSC-derived human neurons to investigate the molecular mechanisms that lead to neurotoxicity induced by vincristine, a common chemotherapeutic used to treat solid tumors. Our results uncover a novel mechanism by which vincristine causes a local increase in mitochondrial proteins that produce reactive oxygen species (ROS) in the axon. Vincristine triggers a cascade of axon pathology, causing mitochondrial dysfunction that leads to elevated axonal ROS levels and SARM1-dependent axon degeneration. Importantly, we show that the neurotoxic effect of increased axonal ROS can be mitigated by the small molecule mitochondrial division inhibitor 1 (mdivi-1) and antioxidants glutathione and mitoquinone, identifying a novel therapeutic avenue to treat the neurological effects of chemotherapy.

The Efficiency of Attentional Networks in Takostubo Syndrome: A Study With the Attentional Network Task for Interaction

Introduction: The role of cardiovascular risk factors in the occurrence and progression of cognitive impairment is relevant in aging studies. In this condition, attention is one of the processes less studied, but preliminary evidence suggests an association between cardiometabolic alterations and attentional decline. Attention is not a unitary process but a set of independent systems (Alerting, Orienting, Executive), which can interact in certain conditions to ensure maximum behavioral efficiency. Methods: We investigated attentive networks and their interactions in patients with Takostubo syndrome (TTS). In all, 20 participants with TTS and 20 individuals without cardiovascular pathologies performed an Attention-Network Task for Interaction, which assesses attentional networks and their interactions. Results: Patients with TTS showed an atypical orienting effect when compared to the control group. Moreover, only the control group exhibited an interaction between orienting and alerting. Conclusion: These findings establish the relevance of brain–heart interaction in identifying attentional impairment as a prodrome of progressively severe cognitive impairment in TTS.

A serum metabolomics study of vascular cognitive impairment patients based on Traditional Chinese medicine syndrome differentiation.

Objective: Vascular cognitive impairment (VCI) accounts for approximately 50%-70% of all dementia cases and poses a significant burden on existing medical systems. Identifying an optimal strategy for preventing VCI and developing efficient symptomatic treatments remains a significant challenge. Syndrome differentiation represents a fundamental approach for personalized diagnosis and treatment in Traditional Chinese Medicine (TCM) and aligns with the principles of precision medicine. The objective of this study was to elucidate the metabolic characteristics of VCI based on TCM syndrome differentiation, thus providing novel insights into the diagnosis and treatment of VCI. Methods: A 2-year cross-sectional cognitive survey was conducted in four communities in Beijing between September 2020 and November 2022. The syndrome differentiation of participants was based on the Kidney-Yang Deficiency Syndrome Scale (KYDSS), which was originally developed by Delphi expert consultation. The identification of serum metabolites was performed by Ultra performance liquid chromatography (UPLC) analysis coupled with an electrospray ionization quadruple time-of-flight mass spectrometer (ESI-QTOF MS). Multivariate, univariate, and pathway analyses were used to investigate metabolic changes. Logistic regression models were also used to construct metabolite panels that were capable of discerning distinct groups. Phospholipase A2 (PLA2) levels were measured by a commercial ELISA kit. Results: A total of 2,337 residents completed the survey, and the prevalence of VCI was 9.84%. Of the patients with VCI, those with Kidney-Yang deficiency syndrome (VCIS) accounted for 70.87% of cases and exhibited more severe cognitive impairments. A total of 80 participants were included in metabolomics study, including 30 with VCIS, 20 without Kidney-Yang deficiency syndrome (VCINS), and 30 healthy control participants (C). Ultimately, 45 differential metabolites were identified when comparing the VCIS group with group C, 65 differential metabolites between the VCINS group and group C, and 27 differential metabolites between the VCIS group and the VCINS group. The downregulation of phosphatidylethanolamine (PE), and phosphatidylcholine (PC) along with the upregulation of lysophosphatidylethanolamine (LPE), lysophosphatidylcholine (LPC), phosphatidic acid (PA) and phospholipase A2 (PLA2) can be considered as the general metabolic characteristics associated with VCI. Dysfunction of glycerophospholipids, particularly LPEs and PCs, was identified as a key metabolic characteristic of VCIS. In particular Glycerophospho-N-Arachidonoyl Ethanolamine (GP-NArE) was discovered for the first time in VCI patients and is considered to represent a potential biomarker for VCIS. The upregulation of PLA2 expression was implicated in the induction of alterations in glycerophospholipid metabolism in both VCIS and VCINS. Moreover, robust diagnostic models were established based on these metabolites, achieving high AUC values of 0.9322, 0.9550, and 0.9450, respectively. Conclusion: These findings contribute valuable information relating to the intricate relationship between metabolic disorders in VCI, neurodegeneration and vascular/neuroinflammation. Our findings also provide a TCM perspective for the precise diagnosis and treatment of VCI in the context of precision medicine.

Behavioral symptoms of Alzheimer’s disease and autism spectrum disorder: Insights to guide future non‐pharmacological interventions

AbstractBackgroundMany behavioral and psychiatric symptoms of dementia (BPSD) share similarities with those described in pediatric autism spectrum disorder (ASD), including anxiety, depression, and communication deficits. However, the possibility of late‐life onset of behaviors stereotypic of ASD in Alzheimer’s disease (AD) has been poorly explored. Findings of three studies are presented here to illustrate associations in behaviors between ASD and AD.MethodsCare partners of persons with cognitive impairment (MCI or dementia) from the University of Kentucky Alzheimer’s Disease Research Center community‐based longitudinal cohort were surveyed using the Gilliam Autism Rating Scale‐2 (GARS‐2). Analyses included t‐tests, chi‐square, analysis of variance, and linear regression models to explore frequency of ASD behaviors in this cohort, and the relationship of behaviors represented in the GARS‐2 compared to behavioral categories used in AD assessment (Neuropsychiatric Inventory‐Questionnaire; NPI‐Q). Lastly, cross‐sectional postmortem neuropathological analyses compared “Autism Possible” to “Autism Unlikely” in available cases.ResultsAnalyses included 142 GARS‐2 respondents. A substantial number of participants presented with ASD‐like behaviors, and those with high Autism Index scores had significantly younger age at onset (71.1±11.0 vs. 76.7±8.3; p = 0.034) and more severe cognitive impairment than those who scored in the “Autism Unlikely” range. ASD‐like behaviors were also significantly correlated with BPSD severity ratings (r = 0.47; p &lt; 0.001). In neuropathological analyses, the two groups differed in the frontal and temporal regions, specific to tau pathology.ConclusionThese findings suggest that ASD‐like behaviors may emerge in AD as a result of shared neurological substrates, given that such behaviors are associated with an earlier age of onset and more severe cognitive impairment. With emerging evidence linking BPSD and ASD, additional research is needed to understand shared mechanisms, as well as development of novel treatment approaches to address behavioral symptoms of AD.

Identifying Optimal Blood Tau Epitopes for the Detection of Alzheimer’s Disease Neuropathology: An Immunoprecipitation Mass Spectrometry and Autopsy Study

AbstractBackgroundPlasma‐to‐autopsy studies are essential for validation of plasma biomarkers for the detection of Alzheimer’s disease (AD). Few such studies have been done and those that exist have had limited or no comparison of the different tau epitopes. This plasma‐to‐autopsy study is the first to use immunoprecipitation mass spectrometry (IP‐MS) to compare the accuracy of eight different plasma tau epitopes (six p‐tau, two total tau) in predicting autopsy‐confirmed AD.MethodThe sample included 123 participants from the Boston University Alzheimer’s Disease Research Center who had an available antemortem plasma sample and donated their brain for neuropathological examination. Plasma samples proximate to death were analyzed for six different plasma p‐tau (181+199+202+205+217+231) and two total tau (t‐tau) epitopes (195‐205, 212‐221) simultaneously using IP‐MS. NIA‐Reagan Institute criteria were used for the neuropathological diagnosis of AD. Binary logistic regressions tested the association between each plasma epitope and autopsy‐confirmed AD status. Area under the receiver operating curve (AUC) statistics were generated using predicted probabilities from the logistic regression models. Analyses were repeated stratified by Clinical Dementia Rating (CDR) score (i.e., &lt;1 and ≥1) at the time of blood draw. Odds Ratio (OR) was used to study associations between the different plasma tau species and CERAD and Braak classifications.Result Table 1 shows sample characteristics. Sixty‐nine of the 123 (56.1%) brain donors had autopsy‐confirmed AD and the average interval between blood draw and death was ∼5 years. Table 2 summarizes logistic regressions and Figure 1 displays ROC curves. Plasma p‐tau217 (AUC = 89.8), p‐tau231 (AUC = 83.4), and p‐tau205 (AUC = 81.3) all had excellent accuracy in discriminating AD from non‐AD brain donors. Among those with CDR≥1, p‐tau217, p‐tau231, and p‐tau205 had outstanding discrimination and all other epitopes had excellent discrimination. Among those with CDR&lt;1, p‐tau217 (AUC = 86.3) and p‐tau231 (AUC = 80.6) still had excellent discrimination accuracy; p‐tau181, p‐tau205, and t‐tau195‐209 had acceptable discrimination. Furthermore, p‐tau217, p‐tau205 and p‐tau231 were the tau species that showed higher ORs with both CERAD (ORp‐tau217 = 15.29, ORp‐tau205 = 5.05 and ORp‐tau231 = 3.86) and Braak staging (ORp‐tau217 = 14.29, ORp‐tau205 = 5.27 and ORp‐tau231 = 4.02).ConclusionPlasma levels of p‐tau217, p‐tau231, and p‐tau205 showed the best discrimination accuracy for AD confirmed neuropathology in both mild and severe cognitive impairment.