Symptoms In Mild Cognitive Impairment Research Articles

Obstructive Sleep Apnea Among Patients with Mild Cognitive Impairment

Background: Obstructive sleep apnea (OSA) is associated with cognitive disorders, but little is known about prevalence of co-occurring OSA and mild cognitive impairment (MCI) as well as about co-occurring OSA and Alzheimer’s disease (AD). Pathophysiological models integrating OSA, cognitive deficits and neurodegeneration remain speculative. Findings in this area could contribute to the knowledge about pathophysiological processes in cognitive disorders and neurodegenerative processes, be helpful for the diagnosis of cognitive disorders and provide approaches for the treatment of cognitive disorders. Objective: Examining the prevalence of OSA and patterns of cognitive deficits as well as AD biomarker profiles associated with OSA in a cohort of 104 MCI patients. Methods: Assessments used include: respiratory polygraphy, The Consortium to Establish a Registry for Alzheimer’s Disease Neuropsychological Battery (CERAD NB), Tau, phosphoTau181, amyloid-β-1–42/1–40, 18F-fluorodeoxyglucose positron emission tomography (F18-FDG-PET). Results: Prevalence of OSA of any severity: 58,7% (Apnea Hypopnea Index (AHI)≥5/h), OSA in a moderate-to-severe extent (AHI≥15/h): 25%. Only 13.1% of MCI patients with OSA reported daytime sleepiness. MCI-OSA patients showed no specific neuropsychological pattern. Presence of OSA was not associated with specific AD biomarker profiles in the whole study group besides a positive association between AD positivity in an AD biomarker sub cohort. Conclusions: OSA is highly prevalent in patients with MCI. It might often remain undiagnosed as only a small number of MCI-OSA patients report daytime sleepiness. OSA could contribute to MCI symptoms and even to AD pathology. Further research is needed to validate these findings and to investigate possible pathophysiological relationships between OSA and MCI as well as between OSA and AD.

A randomized controlled trial on the effects of traditional Thai mind-body exercise (Ruesi Dadton) on biomarkers in mild cognitive impairment.

Exercise has been shown to reduce the rate of mild cognitive impairment (MCI) and Alzheimer's disease. Although motor coordination movements and poses in Ruesi Dadton (RD) exercises may improve cognitive function, RD is rarely used for MCI. To date, there is insufficient evidence on whether 12 weeks of RD exercise correlates with blood biomarkers related to neurogenesis and plasticity. To determine the effects on blood biomarkers of 12-week RD in MCI. Two-group parallel randomized controlled trial. Community exercise. Individual with MCI. Fifty-eight participants (n.=29 in each group). The RD group performed 60min of RD exercises (15 poses) three times weekly for 12 weeks. The control group received no intervention. In addition, both groups were given information regarding MCI symptoms by the physician on the first day. Peripheral blood was collected to measure serum brain-derived neurotrophic factor (BDNF) and sirtuin 1 (SIRT1) levels before and after intervention. The effects of 12-week RD pre- and post-intervention were examined using 2×2 repeated multivariate analyses, which showed significant differences in interaction by group and time. Student's t tests and paired t tests were employed in subsequent analyses to evaluate between-group and within-group differences for both biomarkers. In each test, we discovered increased levels of BDNF and SIRT1 in the RD group but not in the control group. These findings suggested that RD could benefit MCI patients through enhanced BDNF and SIRT1 levels. Twelve weeks of RD might be helpful to patients with MCI and older people who experience cognitive impairment by improving blood biomarkers responsible for brain plasticity and amyloid plaque degradation.

Anosognosia is associated with increased prevalence and faster development of neuropsychiatric symptoms in mild cognitive impairment.

Both the loss of awareness for cognitive decline (a. k.a anosognosia) and neuropsychiatric symptoms (NPS) are common in patients with Alzheimer's disease (AD) dementia, even in prodromal stages, and may exacerbate functional impairment and negatively impact caregiver burden. 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). We included 237 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) with a baseline clinical diagnosis of MCI. Everyday Cognition (ECog) questionnaire scores were used to measure complaints from participants and study-partners at baseline and annually over a mean of 4.29 years [standard deviation (SD) = 2.72]. 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 without more than two consecutive deviating observations during the follow-up period. The 12-item study-partner-rated Neuropsychiatric Inventory determined the presence or absence of specific NPS. Survival analyses were performed to analyze the frequency and temporal onset of NPS over time in individuals with and without anosognosia. Thirty-eight out of 237 participants displayed anosognosia. Groups had similar lengths of follow-up at baseline (p > 0.9), though participants with anosognosia had lower MMSE scores (p = 0.049) and a higher proportion of amyloid-positivity using PET (p < 0.001. At baseline, the frequencies of agitation (p = 0.029) and disinhibition (p < 0.001) were higher in the anosognosia group compared to the non-anosognosia group. Survival analyses showed earlier onset of seven of the 12 NPS in the anosognosia group (p's < 0.001). Loss of awareness for cognitive decline is associated with greater frequency and earlier onset of NPS over time in participants with MCI. These results support the hypothesis of a potential common underlying neurophysiological process for anosognosia and NPS, a finding that needs to be addressed in future studies.

Service provision for older adults living in prison with dementia/mild cognitive impairment in England and Wales: a national survey

ABSTRACT Older adults are the fastest growing age sub-group in prison. Prison, health and social work staff are required to provide support for complex health and social care issues including Dementia and Mild Cognitive Impairment (MCI). Dementia care for those living in the community is a national priority. There is, however, a lack of empirical evidence regarding service provision for those living in prison. This study was the first national survey of England and Wales to establish current service provision. Questionnaires were distributed to heads of healthcare and governors of all prisons in England and Wales. Our response rate was 85 (78%) for governors and 77 (71%) for healthcare managers. Reported prevalence of dementia/MCI from respondents was well below prevalence estimates from research. Furthermore, only 23 prisons (30%) had routine screening, and the majority reported that they did not have a defined care pathway (53; 69%) for dementia/MCI. Overall, the provision of services for those experiencing symptoms of dementia and MCI in prison is sub-optimal; however, many respondents reported aspirations to enhance services for this group. The forthcoming Ministry of Justice’s national strategy for ageing prisons should include recommended care pathways for dementia and MCI to strive towards equivalence of care to community settings.

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&gt;0.01), executive function (P&gt;0.01), receptive language (P&gt;0.01) and memory skills (P&gt;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.

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 &gt; .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 &gt; .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.

Synaptic Marker NPTX2 Predicts Risk of MCI Clinical Symptom Onset

AbstractBackgroundNeuronal pentraxin 2 (NPTX2) is a synaptic protein involved in the homeostatic regulation of cortical network dynamics and synaptic plasticity. Prior cross‐sectional studies suggest that NPTX2 levels decline across the spectrum of Alzheimer’s disease (AD), and that NPTX2 levels can distinguish individuals with normal cognition vs. mild cognitive impairment (MCI) and AD dementia. Less is known about how levels of NPTX2 among individuals with normal cognition relate to future clinical outcomes. To address this, we examined whether baseline levels of NPTX2 predicted time to onset of clinical symptoms of MCI, both alone and in combination with AD biomarkers, among individuals who were cognitively normal at baseline and have undergone 16.3y of follow‐up, on average.MethodCerebrospinal fluid (CSF) was collected at baseline from 269 cognitively normal BIOCARD Study participants (M baseline age = 57.7y), including 77 (29%) who subsequently progressed to MCI or dementia (Table 1). Baseline NPTX2 levels were measured from three highly correlated peptides using quantitative parallel reaction monitoring mass spectrometry. NPTX2 peptide levels were standardized and averaged to create an NPTX2 composite score. Baseline levels of Aβ42/Aβ40, p‐tau181, and t‐tau were measured using Lumipulse automated electrochemiluminescence assays.ResultIn Cox regression models, lower NPTX2 levels were significantly associated with earlier time to MCI clinical symptom onset (HR = 0.76, 95% CI (0.601, 0.962), p = 0.02; Figure 1a). After accounting for CSF AD biomarkers (i.e., Aβ42/Aβ40 and tau), the association between NPTX2 levels and MCI symptom onset appeared stronger (Table 2; Figure 1b). Importantly, NPTX2 did not interact with AD biomarker levels (all p &gt; 0.11) or APOE‐ε4 genetic status (p = 0.71) in relation to MCI symptom onset.ConclusionCSF levels of the synaptic marker NPTX2 predict time to progress to MCI among individuals with normal cognition, suggesting that NPTX2 may be an early prognostic biomarker of synaptic dysfunction. Moreover, this association appears to be additive and independent of AD biomarker levels. Future work is underway to determine if NPTX2 provides resilience to cognitive impairment in the presence of AD pathology, and if there is a differential relationship with markers of amyloid vs. tau.

54 Neuropsychiatric Symptoms in Mild Cognitive Impairment and Dementia with Lewy Bodies

Objective:Neuropsychiatric symptoms (NPS) can be observed in mild cognitive impairment (MCI) and dementia. Hallucinations are a core clinical symptom of Dementia with Lewy Bodies (DLB). In this study, we investigated NPS in healthy control and MCI groups who would later be diagnosed with DLB to determine which symptoms would present early.Participants and Methods:Participants included those originally diagnosed as healthy controls (n=55), MCI with DLB etiology (n=215), and DLB (n=1059). The control and MCI groups progressed to DLB at later visits in the study. NPS data were collected using the Neuropsychiatric Inventory Questionnaire (NPI-Q) that was obtained from the National Alzheimer's Coordinating Center.Results:To determine which NPS presented early in the DLB course, we ran ANCOVAs to assess the role of original diagnosis on each NPS, using age as a covariate and applying Bonferroni correction. The control and MCI groups, who were later diagnosed with DLB, had greater severity of delusions, hallucinations, agitation, and apathy than the DLB group. The MCI group that would later be diagnosed with DLB had greater severity of anxiety and motor symptoms than the DLB group. The control group had greater irritability severity than the DLB group, and the controls had greater nighttime behavior severity than the MCI group, who had greater severity than the DLB group.Conclusions:Overall, we found that NPS present early in those who will be diagnosed with DLB, even when they are diagnosed as healthy controls. These results suggest that examination of NPS is important even in healthy adults, and their presence may be the onset of the DLB process before an official diagnosis of the condition.

Cerebrospinal Fluid Alzheimer's Disease Biomarker Patterns of Change Prior to the Onset of Mild Cognitive Impairment.

Cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) are altered many years before the onset of clinical symptoms of mild cognitive impairment (MCI). Incorporating clinical symptom onset time into biomarker modeling may enhance our understanding of changes preceding MCI. Using a new analytical approach, we examined patterns of biomarker change prior to MCI symptom onset among individuals who progressed from normal cognition to MCI, stratified based on the age of symptom onset. We also analyzed biomarker patterns of change among participants who remained cognitively normal, and examined potential modifiers of biomarker trajectories, including demographics and apolipoprotein E (APOE) status. Analyses included 93 participants who progressed from normal cognition to MCI and 186 participants who remained cognitively normal, over an average follow-up period of 16.2 years. CSF biomarkers, including Aβ42, Aβ40, total tau (t-tau), and phosphorylated tau181 (p-tau181), were measured using the fully automated Lumipulse assays. Among participants who progressed to MCI, Aβ42/Aβ40 decreased, and t-tau and p-tau181 increased. For participants who did not progress to MCI, CSF biomarkers showed relatively stable patterns. In both progressors and non-progressors, APOE4 carriers showed lower Aβ 42/Aβ40 levels (compared to non-carriers) at each point of the mean curves. Among non-progressors, APOE4 carriers had higher levels of p-tau181, p-tau181/(Aβ 42/Aβ40), and t-tau/(Aβ 42/Aβ 40). Additionally, among those who did not progress, female sex was associated with higher levels of t-tau, p-tau181, t-tau/(Aβ 42/Aβ 40), and p-tau181/(Aβ 42/Aβ 40). These findings suggest that this analytic approach may provide additional insights into biomarker changes during early phases of AD.

Network analysis of neuropsychiatric symptoms in Alzheimer’s disease

BackgroundNeuropsychiatric symptoms due to Alzheimer’s disease (AD) and mild cognitive impairment (MCI) can decrease quality of life for patients and increase caregiver burden. Better characterization of neuropsychiatric symptoms and methods of analysis are needed to identify effective treatment targets. The current investigation leveraged the National Alzheimer’s Coordinating Center (NACC) Uniform Data Set (UDS) to examine the network structure of neuropsychiatric symptoms among symptomatic older adults with cognitive impairment.MethodsThe network relationships of behavioral symptoms were estimated from Neuropsychiatric Inventory Questionnaire (NPI-Q) data acquired from 12,494 older adults with MCI and AD during their initial visit. Network analysis provides insight into the relationships among sets of symptoms and allows calculation of the strengths of the relationships. Nodes represented individual NPI-Q symptoms and edges represented the pairwise dependency between symptoms. Node centrality was calculated to determine the relative importance of each symptom in the network.ResultsThe analysis showed patterns of connectivity among the symptoms of the NPI-Q. The network (M = .28) consisted of mostly positive edges. The strongest edges connected nodes within symptom domain. Disinhibition and agitation/aggression were the most central symptoms in the network. Depression/dysphoria was the most frequently endorsed symptom, but it was not central in the network.ConclusionsNeuropsychiatric symptoms in MCI and AD are highly comorbid and mutually reinforcing. The presence of disinhibition and agitation/aggression yielded a higher probability of additional neuropsychiatric symptoms. Interventions targeting these symptoms may lead to greater neuropsychiatric symptom improvement overall. Future work will compare neuropsychiatric symptom networks across dementia etiologies, informant relationships, and ethnic/racial groups, and will explore the utility of network analysis as a means of interrogating treatment effects.

NPTX2 in Cerebrospinal Fluid Predicts the Progression From Normal Cognition to Mild Cognitive Impairment.

This study examined whether cerebrospinal fluid (CSF) baseline levels of the synaptic protein NPTX2 predict time to onset of symptoms of mild cognitive impairment (MCI), both alone and when accounting for traditional CSF Alzheimer's disease (AD) biomarker levels. Longitudinal NPTX2 levels were also examined. CSF was collected longitudinally from 269 cognitively normal BIOCARD Study participants (mean baseline age = 57.7 years; mean follow-up = 16.3 years; n = 77 progressed to MCI/dementia). NPTX2 levels were measured from 3 correlated peptides using quantitative parallel reaction monitoring mass spectrometry. Levels of Aβ42 /Aβ40 , p-tau181 , and t-tau were measured from the same CSF specimens using Lumipulse automated electrochemiluminescence assays. In Cox regression models, lower baseline NPTX2 levels were associated with an earlier time to MCI symptom onset (hazard ratio [HR] = 0.76, SE = 0.09, p = 0.023). This association was significant for progression within 7 years (p = 0.036) and after 7 years from baseline (p = 0.001). Baseline NPTX2 levels improved prediction of time to MCI symptom onset after accounting for baseline AD biomarker levels (p < 0.01), and NPTX2 did not interact with the CSF AD biomarkers or APOE-ε4 genetic status. In linear mixed effects models, higher baseline p-tau181 and t-tau levels were associated with higher baseline levels of NPTX2 (both p < 0.001) and greater rates of NPTX2 declines over time. NPTX2 may be a valuable prognostic biomarker during preclinical AD that provides additive and independent prediction of MCI onset among individuals who are cognitively normal. We hypothesize that NPTX2-mediated circuit homeostasis confers resilience during the early phase of AD. ANN NEUROL 2023;94:620-631.

Bidirectional association between depressive symptoms and mild cognitive impairment over 20 years: Evidence from the Health and Retirement Study in the United States

BackgroundResearch examining the association between depressive symptoms and mild cognitive impairment (MCI) has yielded conflicting results. This study aimed to examine the bidirectional association between depressive symptoms and MCI, and the extent to which this bidirectional association is moderated by gender and education. MethodsData come from the US Health and Retirement Study over a 20-year period (older adults aged ≥50 years). Competing-risks regression is employed to examine the association between baseline high-risk depressive symptoms and subsequent MCI (N = 9317), and baseline MCI and subsequent high-risk depressive symptoms (N = 9428). Interactions of baseline exposures with gender and education are tested. ResultsAfter full adjustment, baseline high-risk depressive symptoms were significantly associated with subsequent MCI (SHR = 1.20, 95%CI 1.08–1.34). Participants with baseline MCI are more likely to develop subsequent high-risk depressive symptoms than those without baseline MCI (SHR = 1.16, 95%CI 1.01–1.33). Although gender and education are risk factors for subsequent depression and MCI, neither moderates the bidirectional association. LimitationsItems used to construct the composite cognitive measure are limited; selection bias due to missing data; and residual confounding. ConclusionsOur study found a bidirectional association between depressive symptoms and MCI. High-risk depressive symptoms are related to a higher risk of subsequent MCI; and MCI predicts subsequent high-risk depression. Though neither gender nor education moderated the bidirectional association, public health interventions crafted to reduce the risk of depression and MCI should pivot attention to older women and those with less formal education.

Auditory hallucinations of Buddhist chanting as an initial symptom of mild cognitive impairment with Lewy bodies.

The authors declare there are no competing interests. The data that support the findings of this study are available from the corresponding author upon reasonable request.

Longitudinal associations of emergent and persistent affective dysregulation symptoms with incident dementia in dementia‐free older adults

AbstractBackgroundNeuropsychiatric symptoms (NPS) are risk factors for dementia. Mild behavioral impairment (MBI) is a neurobehavioral syndrome that refines NPS assessment to improve dementia prognostication by identifying later‐life emergent and persistent NPS specifically as the at‐risk group. Affective dysregulation contributes to dementia risk and is an MBI domain characterized by the inability to regulate emotions. Here, we investigate the longitudinal association of MBI‐affective dysregulation with incident dementia in dementia‐free older adults from the National Alzheimer Coordinating Centre (NACC).MethodNACC participants with no history of psychiatric, neurological, or neurodevelopmental disorders were included. MBI‐affective dysregulation status was determined based on Neuropsychiatric Inventory Questionnaire (NPI‐Q) depression, anxiety, and elation scores at two consecutive visits. The comparator group involved participants with no NPS prior to dementia. Participants with dementia at baseline were excluded from the study. Kaplan‐Meier curves of dementia‐free survival over ten years were generated for MBI‐affective dysregulation versus no NPS. Cox proportional hazard models were implemented to assess the risk of dementia, adjusted for age, sex, years of education, race, APOE e4 status, and clinical cognitive diagnosis. Potential interactions were further explored for relevant model covariates.ResultThe final sample consisted of 3,446 participants with no NPS (mean age 73.1; 63.0% female), and 1,156 with MBI‐affective dysregulation (mean age 75.1; 53.9% female). MBI‐affective dysregulation was associated with lower chance of dementia‐free survival (log rank, p&lt;0.001) and 1.67 times greater risk of dementia compared to no NPS (CI:1.4‐2, p&lt;0.001). Moderation analysis revealed that in participants with normal cognition (NC), those with MBI‐affective dysregulation were at 2.56 times greater risk of dementia than those with no NPS (CI:1.87‐3.49, p&lt;0.001). In mild cognitive impairment (MCI), the risk associated with MBI‐affective dysregulation was 1.4 times greater than no NPS (CI:1.14‐1.72, p = 0.02).ConclusionThe emergence of persistent affective dysregulation symptoms in dementia‐free older adults is associated with substantial risk for dementia. When emerging in individuals with NC, these persistent affective symptoms represent a greater risk compared to those with no NPS, compared to emergence of these symptoms in MCI. MBI‐affective dysregulation is an important risk factor for dementia and should be considered in clinical assessments.

Neuropsychiatric symptoms in mild cognitive impairment and Alzheimer’s disease: Relation with disease stage, sex, and daily function impairment

AbstractBackgroundTo reveal the relations between neuropsychiatric symptoms (NPS), stages of cognitive impairment, sex, and daily function impairment in patients with mild cognitive impairment (MCI) and Alzheimer’s disease (AD).Method1,154 patients with MCI and AD were enrolled from 2014 to 2021 from the Memory Clinic, The First Affiliated Hospital of Chongqing Medical University. Mini‐mental State Examination (MMSE) was used to assess the cognitive function, and Clinical dementia rating scale (CDR) was used to evaluate the disease severity of patients. NPS and function of patients’ daily life were evaluated by Neuropsychiatric Inventory (NPI) and activities of daily living (ADL) respectively.ResultPsychosis symptoms displayed the highest prevalence in MCI (43.3%) and mild AD stage (62.2%), while in moderate and severe AD, behavior symptoms showed its dominance (86.7% and 96.4%, respectively). Delusion, apathy, AMB and sleep disturbance were the discriminant symptoms across the spectrum of cognitive decline (all P &lt;0.05). Depression was more prominent in female (26.1% vs. 14.9% in MCI; 40.2% vs. 21.0% in AD, all P&lt; 0.05) while male patients presented higher prevalence in apathy (27.0% vs. 18.6% in MCI; 54.1% vs. 42.8% in AD, all P&lt; 0.05). Physical self‐maintenance was negatively impacted by apathy and sleep disturbance at mild AD stage, while instrumental activity of daily living was significantly influenced by aberrant motor behavior in MCI and mild AD (all P&lt; 0.05).ConclusionThe prevalence of NPS is correlated with sex, the stage of cognitive impairment and daily living function. Revealing their relations can allow he development of better prevention and treatment strategies for patients with cognitive impairment.