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1.
Alzheimers Dement ; 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38958543

ABSTRACT

INTRODUCTION: We examined the burden of neuropsychiatric symptoms (NPSs) in early-onset (EO) and late-onset (LO) Alzheimer's disease (AD) and adjusted for age effects via the inclusion of cognitively unimpaired (CU) individuals. METHODS: Cross-sectional data from 2940 EOAD, 8665 LOAD, and 8775 age-stratified CU individuals (early-CU, n = 2433; late-CU, n = 6342) from the National Alzheimer's Coordinating Center database were included. Fisher's exact tests compared EOAD and LOAD on the presence and severity of NPSs. Multiple logistic regression models included an age*diagnosis interaction to examine age effects. RESULTS: Presence (ps < 0.0001) and severity (ps < 0.05) of NPS were greater in EOAD than in LOAD. However, after adjusting for base rates in NPS in CU individuals (age effects), only elation and eating behaviors were more frequent in EOAD (ps < 0.05) and nighttime behaviors more frequent and severe in LOAD (ps < 0.05). DISCUSSION: Few NPSs were specific to the EOAD versus LOAD. Previous findings of greater NPS burden in EOAD may partially reflect age effects. HIGHLIGHTS: Adjusting for age effect, elation and eating problems are more frequent in EOAD. Adjusting for age effect, sleep disturbances are more frequent and severe in LOAD. Age effects underlie higher neuropsychiatric symptom presentation in EOAD than in LOAD.

2.
medRxiv ; 2024 May 27.
Article in English | MEDLINE | ID: mdl-38854100

ABSTRACT

INTRODUCTION: A recently developed mild behavioral impairment (MBI) diagnostic framework standardizes the early characterization of neuropsychiatric symptoms in older adults. However, the links between MBI, brain function, and Alzheimer's disease (AD) biomarkers are unclear. METHODS: Using data from 128 participants with diagnosis of amnestic mild cognitive impairment and mild dementia - Alzheimer's type, we test a novel model assessing direct relationships between AD biomarker status and MBI symptoms, as well as mediated effects through segregation of the salience and default-mode networks. RESULTS: We identified a mediated effect of tau positivity on MBI through functional segregation of the salience network from the other high-level, association networks. There were no direct effects of AD biomarkers status on MBI. DISCUSSION: Our findings suggest an indirect role of tau pathology in MBI through brain network dysfunction and emphasize the role of the salience network in mediating relationships between neuropathological changes and behavioral manifestations.

3.
Alzheimers Dement ; 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38877658

ABSTRACT

BACKGROUND: The mechanisms linking mild behavioral impairment (MBI) and Alzheimer's disease (AD) have been insufficiently explored, with conflicting results regarding tau protein and few data on other metabolic markers. We aimed to evaluate the longitudinal association of the MBI domains and a spectrum of plasma biomarkers. METHODS: Our study is a secondary analysis of data from NOLAN. The longitudinal association of the MBI domains with plasma biomarkers, including pTau181, was tested using adjusted linear mixed-effects models. RESULTS: The sample comprised 359 participants (60% female, mean age: 78.3, standard deviation: 0.3 years). After 1 year, the MBI domain of abnormal perception was associated with steeper increases in plasma pTau181. Abnormal perception, decreased motivation, and impulse dyscontrol were associated with homocysteine or insulin dysregulation. DISCUSSION: Apart from the association with plasma pTau181, our results suggest that MBI might also represent metabolic dysregulation, probably contributing to dementia transition among older adults with subjective cognitive decline or mild cognitive impairment. HIGHLIGHTS: Mild behavioral impairment (MBI) psychosis was associated with steeper increases in plasma p. pTau could be a pharmacological target to treat agitation and psychosis symptoms. MBI domains were linked to metabolic dysregulation involving insulin and homocysteine.

4.
J Neurol ; 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38884789

ABSTRACT

BACKGROUND: Recent studies propose 40 Hz neural activity induction as a promising approach for managing Alzheimer's dementia (AD). However, traditional flickering light is suboptimal in addressing cognitive and neuropsychiatric symptoms (NPS) of AD. This study aims to investigate the clinical efficacy of a novel multi-luminaire lighting technology, with reduced perceptible flickering, for treating AD NPS. METHODS: This study is a prospective, convenient sampling, non-randomized case-control investigation involving seventy-eight clinically diagnosed AD patients from 7 daycare centers. Thirty-five were exposed to 40 Hz light through Delta M + BrainCare Light (M +), 4 h daily, 5 days/week, for 12 weeks. The other 43 patients served as controls. Sum of boxes of the Clinical Dementia Rating (CDR-SB) scale, Neuropsychiatric Inventory (NPI), and Zarit Burden Interview (ZBI) were assessed at baseline and the 13th week. RESULTS: At baseline, the cases had worse cognitive function, lower cognitive score (Mini-Mental State Examination, p = 0.04; Cognitive Abilities Screening Instrument, p = 0.04), and advanced caregiver burden with higher ZBI scores (p < 0.01) than the controls. After the intervention, the cases had significant improvements in NPS as assessed using the NPI (p = 0.02), especially depression and euphoria symptoms (p = 0.04 and < 0.01, respectively) and less caregiver burden (ZBI score, p < 0.01). In global function, the control group showed a significant decline in CDR-SB score (p < 0.01), while the cases did not. CONCLUSIONS: Results suggest M + may slow global function decline, preserve cognitive function, improve NPS, and reduce caregiver burden in AD patients. Larger studies with biomarkers are needed to explore underlying mechanisms.

5.
Br J Haematol ; 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38924051

ABSTRACT

Steroids are a mainstay in the treatment of acute lymphoblastic leukaemia (ALL) in children and adolescents; however, their use can cause clinically significant steroid-related neuropsychiatric symptoms (SRNS). As current knowledge on SRNS during ALL treatment is limited, we mapped the phenotypes, occurrence and treatment strategies using a database created by the international Ponte di Legno Neurotoxicity Working Group including data on toxicity in the central nervous system (CNS) in patients treated with frontline ALL protocols between 2000 and 2017. Ninety-four of 1813 patients in the CNS toxicity database (5.2%) experienced clinically significant SRNS with two peaks: one during induction and one during intensification phase. Dexamethasone was implicated in 86% of SRNS episodes. The most common symptoms were psychosis (52%), agitation (44%) and aggression (31%). Pharmacological treatment, mainly antipsychotics and benzodiazepines, was given to 87% of patients while 38% were hospitalised due to their symptoms. Recurrence of symptoms was reported in 29% of patients and two previously healthy patients required ongoing pharmacological treatment at the last follow up. Awareness of SRNS during ALL treatment and recommendation on treatment strategies merit further studies and consensus.

6.
Clin Neuropsychol ; : 1-23, 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38914594

ABSTRACT

Objective: Multiple sclerosis (MS) may include not only severe neurological signs and symptoms, but also cognitive and psychiatric disturbances. When psychiatric symptoms precede or are comorbid with MS, it poses a clinical challenge, because it may lead to a mistaken diagnosis of MS as a psychiatric disorder, delaying proper treatment. We describe the neuropsychological profile of a female patient with MS whose diagnosis was delayed due to neuropsychiatric symptoms. Method: A comprehensive analysis of the medical history and the results of a teleneuropsychological assessment of a 36-year-old Mexican woman with a diagnosis of relapsing--remitting MS (RRMS) was performed. Results: The patient indicates a long history of psychotic, anxious, and depressive features years before the first neurological symptom that led to MS going unnoticed for several years. Language, attentional, perceptual, motor, and learning skills were found to be preserved. Short-term memory and spatial orientation problems were identified, with decreased processing speed and executive dysfunction, including working memory and planning deficits. Conclusions: The patient has a non-typical presentation of neuropsychological alterations with cognitive and behavioral symptoms that resemble dorsolateral frontal lobe syndrome. This case study highlights the importance of considering MS in differential diagnosis of patients with psychiatric symptoms, even in the absence of obvious neurological signs.

7.
J Alzheimers Dis ; 100(1): 193-205, 2024.
Article in English | MEDLINE | ID: mdl-38848176

ABSTRACT

Background: The NIA-AA Research Framework on Alzheimer's disease (AD) proposes a transitional stage (stage 2) characterized by subtle cognitive decline, subjective cognitive decline (SCD) and mild neurobehavioral symptoms (NPS). Objective: To identify participant clusters based on stage 2 features and assess their association with amyloid positivity in cognitively unimpaired individuals. Methods: We included baseline data of N = 338 cognitively unimpaired participants from the DELCODE cohort with data on cerebrospinal fluid biomarkers for AD. Classification into the AD continuum (i.e., amyloid positivity, A+) was based on Aß42/40 status. Neuropsychological test data were used to assess subtle objective cognitive dysfunction (OBJ), the subjective cognitive decline interview (SCD-I) was used to detect SCD, and the Neuropsychiatric Inventory Questionnaire (NPI-Q) was used to assess NPS. A two-step cluster analysis was carried out and differences in AD biomarkers between clusters were analyzed. Results: We identified three distinct participant clusters based on presented symptoms. The highest rate of A+ participants (47.6%) was found in a cluster characterized by both OBJ and SCD. A cluster of participants that presented with SCD and NPS (A+:26.6%) and a cluster of participants with overall few symptoms (A+:19.7%) showed amyloid positivity in a range that was not higher than the expected A+ rate for the age group. Across the full sample, participants with a combination of SCD and OBJ in the memory domain showed a lower Aß42/ptau181 ratio compared to those with neither SCD nor OBJ. Conclusions: The cluster characterized by participants with OBJ and concomitant SCD was enriched for amyloid pathology.


Subject(s)
Alzheimer Disease , Amyloid beta-Peptides , Biomarkers , Cognitive Dysfunction , Neuropsychological Tests , Peptide Fragments , Humans , Male , Female , Amyloid beta-Peptides/cerebrospinal fluid , Amyloid beta-Peptides/metabolism , Aged , Cognitive Dysfunction/cerebrospinal fluid , Cognitive Dysfunction/psychology , Cognitive Dysfunction/diagnosis , Biomarkers/cerebrospinal fluid , Peptide Fragments/cerebrospinal fluid , Alzheimer Disease/cerebrospinal fluid , Alzheimer Disease/psychology , Alzheimer Disease/diagnosis , Middle Aged , Cohort Studies , Aged, 80 and over , Cluster Analysis
8.
Expert Opin Emerg Drugs ; : 1-15, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38822731

ABSTRACT

INTRODUCTION: Agitation, psychosis, and apathy are prevalent and highly distressing neuropsychiatric symptoms (NPS) of Alzheimer's disease (AD) that have been linked to numerous negative outcomes, including increased mortality, worsened cognitive decline, and caregiver burden. Current treatments for AD-associated agitation, namely atypical antipsychotics, provide some benefits but may increase the risk of serious adverse events and death. Meanwhile, no pharmacotherapies have been approved by regulatory agencies for the treatment of psychosis or apathy in AD. Over the past decade, many new and repurposed drugs have emerged as potential therapeutic options for managing these challenging NPS. AREAS COVERED: This review aims to provide a comprehensive summary of pharmacotherapies that have recently been investigated in phase 2 and 3 clinical trials for the treatment of agitation, psychosis, or apathy in AD. EXPERT OPINION: Novel atypical antipsychotics, serotonergic antidepressants, cannabinoids, and dextromethorphan combination drugs have shown promising results for alleviating agitation. Pimavanserin appears to be the most effective emerging therapy for psychosis, while methylphenidate has demonstrated good efficacy for apathy. Further research on biomarkers of NPS severity and treatment response, as well as continued improvements in methodological approaches are needed to advance the field.

9.
J Neuroimmunol ; 392: 578369, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38823118

ABSTRACT

Neuropsychiatric symptoms in N-methyl-d-aspartate receptor encephalitis (NMDARE) have led some to pursue empiric trials of electroconvulsive therapy (ECT). A scoping review identified 39 patients diagnosed with NMDARE undergoing ECT. Separately, a retrospective cohort was reviewed to characterize 21 patients. Clinical improvement was attributed to ECT in 49% of patients in the scoping review and 19% of patients in the retrospective cohort; timing of immunotherapies was a confounding factor. Worsening of clinical course following ECT was reported in 28% of patients in the scoping review and 38% of patient in the retrospective review. There is currently insufficient data supporting a beneficial effect of ECT in NMDARE.


Subject(s)
Anti-N-Methyl-D-Aspartate Receptor Encephalitis , Electroconvulsive Therapy , Humans , Anti-N-Methyl-D-Aspartate Receptor Encephalitis/therapy , Electroconvulsive Therapy/methods , Retrospective Studies , Female , Male , Adult , Young Adult , Middle Aged , Cohort Studies , Adolescent , Treatment Outcome
10.
Article in English | MEDLINE | ID: mdl-38847905

ABSTRACT

Long COVID, a condition characterized by persistent symptoms after COVID-19 infection, is increasingly being recognized worldwide. Neurologic symptoms are frequently reported in survivors of COVID-19, making it crucial to better understand this phenomenon both on a societal scale and for the quality of life of these patients. Between January 1, 2020, and July 31, 2022, Illinois (IL) had a standardized cumulative death rate that ranked it 24th out of the 51 states in the United States (US). However, the US had one of the highest per capita COVID-19 death rates among large, high-income countries. [Bollyky T. et al. 2023] As a result of the increased number of COVID-19 infections, there was a rise in the number of patients experiencing Long COVID. At our neuro-infectious disease clinic in Chicago (IL), we observed an increasing number of patients presenting with cognitive and other neurologic symptoms after contracting COVID-19. Initially, we needed to provide these individuals with a better understanding of their condition and expected outcomes. We were thus motivated to further evaluate this group of patients for any patterns in presentation, neurologic findings, and diagnostic testing that would help us better understand this phenomenon. We aim to contribute to the growing body of research on Long COVID, including its presentation, diagnostic testing results, and outcomes to enlighten the long COVID syndrome. We hypothesize that the neurological symptoms resulting from long COVID persist for over 12 months. We conducted a retrospective analysis of clinical data from 44 patients with long-COVID. Cognitive symptoms were the most common presenting concern. Abnormalities in Montreal Cognitive Assessment, electroencephalogram, serum autoantibody testing, and cerebrospinal fluid were found in minority subsets of our cohort. At 12 months, most patients continue to experience neurologic symptoms, though more than half reported moderate or marked improvement compared to initial presentation. Although most of the patients in this study did not show a consistent occurrence of symptoms suggesting a cohesive underlying etiology, our clinical data demonstrated some features of Long COVID patients in Chicago (IL) that could lead to new research avenues, helping us better understand this syndrome that affects patients worldwide.

12.
J Clin Med ; 13(12)2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38929966

ABSTRACT

Background/Objectives: Huntington's disease (HD) is an autosomal dominant genetic disorder causing progressive neurodegeneration which, aside from symptomatic therapies for controlling psychological and motor problems, currently has no effective treatment. People who receive this diagnosis often feel disoriented and lost without guidance. Furthermore, HD patients are estimated to have a two to seven times greater risk of suicide death compared to the general population. The current review investigates the complex relationship between HD and suicide, seeking to identify key risk factors influencing suicidal ideation and behaviour in affected individuals. Methods: We conducted a systematic review following the PRISMA guidelines. Studies were searched for on the PubMed, Cochrane, and Web of Science databases, and 17 articles met the inclusion criteria. Results: The findings reveal that emotional strain, neuropsychiatric symptoms, and the absence of a cure contribute to heightened suicidal tendencies in HD patients. Critical periods for suicide risk coincide with early symptomatic stages of disease or the successive phase, with the loss of independence impacting on daily functioning. Risk factors associated with HD include a depressive mood, cognitive impairments, and a history of suicide attempts. Conclusions: From a prevention perspective, a comprehensive multidisciplinary and multidimensional approach could enhance the overall well-being of people with HD. In particular, screening for suicidal thoughts in people with HD could mitigate suicide risk.

13.
JMIR Nurs ; 7: e54496, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38805252

ABSTRACT

BACKGROUND: The behavioral and psychological symptoms of dementia (BPSD) are common among people with dementia and have multiple negative consequences. Artificial intelligence-based technologies (AITs) have the potential to help nurses in the early prodromal detection of BPSD. Despite significant recent interest in the topic and the increasing number of available appropriate devices, little information is available on using AITs to help nurses striving to detect BPSD early. OBJECTIVE: The aim of this study is to identify the number and characteristics of existing publications on introducing AITs to support nursing interventions to detect and manage BPSD early. METHODS: A literature review of publications in the PubMed database referring to AITs and dementia was conducted in September 2023. A detailed analysis sought to identify the characteristics of these publications. The results were reported using a narrative approach. RESULTS: A total of 25 publications from 14 countries were identified, with most describing prospective observational studies. We identified three categories of publications on using AITs and they are (1) predicting behaviors and the stages and progression of dementia, (2) screening and assessing clinical symptoms, and (3) managing dementia and BPSD. Most of the publications referred to managing dementia and BPSD. CONCLUSIONS: Despite growing interest, most AITs currently in use are designed to support psychosocial approaches to treating and caring for existing clinical signs of BPSD. AITs thus remain undertested and underused for the early and real-time detection of BPSD. They could, nevertheless, provide nurses with accurate, reliable systems for assessing, monitoring, planning, and supporting safe therapeutic interventions.


Subject(s)
Artificial Intelligence , Dementia , Humans , Dementia/diagnosis , Dementia/nursing
14.
JMIR Form Res ; 8: e53192, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38717798

ABSTRACT

BACKGROUND: Apathy, depression, and anxiety are prevalent neuropsychiatric symptoms experienced by older adults. Early detection, prevention, and intervention may improve outcomes. OBJECTIVE: We aim to demonstrate the feasibility of deploying web-based weekly questionnaires inquiring about the behavioral symptoms of older adults with normal cognition, mild cognitive impairment, or early-stage dementia and to demonstrate the feasibility of deploying an in-home technology platform for measuring participant behaviors and their environment. METHODS: The target population of this study is older adults with normal cognition, mild cognitive impairment, or early-stage dementia. This is an observational, longitudinal study with a study period of up to 9 months. The severity of participant behavioral symptoms (apathy, depression, and anxiety) was self-reported weekly through web-based surveys. Participants' digital biomarkers were continuously collected at their personal residences and through wearables throughout the duration of the study. The indoor physical environment at each residence, such as light level, noise level, temperature, humidity, or air quality, was also measured using indoor environmental sensors. Feasibility was examined, and preliminary correlation analysis between the level of symptoms and the digital biomarkers and between the level of symptoms and the indoor environment was performed. RESULTS: At 13 months after recruitment began, a total of 9 participants had enrolled into this study. The participants showed high adherence rates in completing the weekly questionnaires (response rate: 275/278, 98.9%), and data collection using the digital technology appeared feasible and acceptable to the participants with few exceptions. Participants' severity of behavioral symptoms fluctuated from week to week. Preliminary results show that the duration of sleep onset and noise level are positively correlated with the anxiety level in a subset of our participants. CONCLUSIONS: This study is a step toward more frequent assessment of older adults' behavioral symptoms and holistic in situ monitoring of older adults' behaviors and their living environment. The goal of this study is to facilitate the development of objective digital biomarkers of neuropsychiatric symptoms and to identify in-home environmental factors that contribute to these symptoms.

15.
Brain Behav ; 14(5): e3532, 2024 May.
Article in English | MEDLINE | ID: mdl-38779749

ABSTRACT

BACKGROUND: Neurocognitive and psychiatric disorders have been proved that they can comorbid more often with idiopathic normal pressure hydrocephalus (iNPH) than general population. However, the potential causal association between these disorders and iNPH has not been assessed. Thus, our study aims to investigate the causal relationship between them based on a bidirectional Mendelian randomization (MR) analysis. METHODS: Random effects of the inverse variance weighted (IVW) method were conducted to obtain the causal association among the neurocognitive disorders, psychiatric disorders, and iNPH. Genome-wide association studies (GWAS) of 12 neurocognitive and psychiatric disorders were downloaded via the OpenGWAS database, GWAS Catalog, and Psychiatric Genomics Consortium, whereas GWAS data of iNPH were obtained from the FinnGen consortium round 9 release, with 767 cases and 375,610 controls of European ancestry. We also conducted the sensitivity analysis in these significant causal inferences using weighted median model, Cochrane's Q test, MR-Egger regression, MR Pleiotropy Residual Sum and Outlier detect and the leave-one-out analysis. RESULTS: For most of the neurocognitive and psychiatric disorders, no causal association was established between them and iNPH. We have found that iNPH (odds ratio [OR] = 1.030, 95% confidence interval [CI]: 1.011-1.048, p = .001) is associated with increased risk for schizophrenia, which failed in validation of sensitivity analysis. Notably, genetically predicted Parkinson's disease (PD) is associated with increased risk of iNPH (OR = 1.256, 95% CI: 1.045-1.511, p = .015). CONCLUSION: Our study has revealed the potential causal effect in which PD associated with an increased risk of iNPH. Further study is warranted to investigate the association between PD and iNPH and the potential underlying mechanism.


Subject(s)
Genome-Wide Association Study , Hydrocephalus, Normal Pressure , Mendelian Randomization Analysis , Mental Disorders , Humans , Hydrocephalus, Normal Pressure/genetics , Hydrocephalus, Normal Pressure/epidemiology , Mental Disorders/genetics , Mental Disorders/epidemiology , Neurocognitive Disorders/genetics , Neurocognitive Disorders/epidemiology
16.
J Geriatr Psychiatry Neurol ; : 8919887241254470, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38769750

ABSTRACT

BACKGROUND: Neuropsychiatric symptoms affect the majority of dementia patients. Past studies report high rates of potentially inappropriate prescribing of psychotropic medications in this population. We investigate differences in neuropsychiatric diagnoses and psychotropic medication prescribing in a local US cohort by sex and race. METHODS: We utilize Medicare claims and prescription fill records in a cohort of 100% Medicare North and South Carolina beneficiaries ages 50 and above for the year 2017 with a dementia diagnosis. We identify dementia and quantify diagnosis of anxiety, depression and psychosis using validated coding algorithms. We search Medicare claims for antianxiety, antidepressant and antipsychotic medications to determine prescriptions filled. RESULTS: Anxiety and depression were diagnosed at higher rates in White patients; psychosis at higher rates in Black patients. (P < .001) Females were diagnosed with anxiety, depression and psychosis at higher rates than males (P < .001) and filled more antianxiety and antidepressant medications than males. (P < .001) Black and Other race patients filled more antipsychotic medications for anxiety, depression and psychosis than White patients. (P < .001) Antidepressants were prescribed at higher rates than antianxiety or antipsychotic medications across all patients and diagnoses. Of patients with no neuropsychiatric diagnosis, 11.4% were prescribed an antianxiety medication, 22.8% prescribed an antidepressant and 7.6% prescribed an antipsychotic. CONCLUSIONS: The high fill rate of antianxiety (benzodiazepine) medications in dementia patients, especially females is a concern. Patients are prescribed psychotropic medications at high rates. This practice may represent potentially inappropriate prescribing. Patient/caregiver education with innovative community outreach and care delivery models may help decrease medication use.

17.
Am J Hosp Palliat Care ; : 10499091241253838, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38714329

ABSTRACT

End-of-life (EOL) care has been a common option for patients with terminal medical conditions such as cancers. However, the utilization of EOL care in Alzheimer disease and other dementing conditions have become available relatively recently. As the end-stage dementia approaches, the clinicians and caregivers become faced with numerous clinical challenges-delirium, neuropbehavioral symptoms, the patient's inability to communicate pain and associated discomfort, food refusal, and so on. In addition to providing quality clinical care to the EOL patients, clinicians should pay special attention to their families, assuring that their loved ones will receive supportive measures to improve quality of life (QOL).

18.
Trends Mol Med ; 2024 May 30.
Article in English | MEDLINE | ID: mdl-38821772

ABSTRACT

Neuropsychiatric symptoms (NPSs) in Alzheimer's disease (AD) constitute multifaceted behavioral manifestations that reflect processes of emotional regulation, thinking, and social behavior. They are as prevalent in AD as cognitive impairment and develop independently during the progression of neurodegeneration. As studying NPSs in AD is clinically challenging, most AD research to date has focused on cognitive decline. In this opinion article we summarize emerging literature on the prevalence, time course, and the underlying genetic, molecular, and pathological mechanisms related to NPSs in AD. Overall, we propose that NPSs constitute a cluster of core symptoms in AD, and understanding their neurobiology can lead to a more holistic approach to AD research, paving the way for more accurate diagnostic tests and personalized treatments embracing the goals of precision medicine.

19.
Front Psychiatry ; 15: 1231361, 2024.
Article in English | MEDLINE | ID: mdl-38800068

ABSTRACT

Background: Neuropsychiatric symptoms (NPSs) are a distressful aspect of dementia and the knowledge of structural correlates of NPSs is limited. We aimed to identify associations of fronto-limbic circuit with specific NPSs in patients with various types of cognitive impairment. Methods: Of 84 participants, 27 were diagnosed with mild cognitive impairment (MCI), 41 with Alzheimer's disease (AD) dementia and 16 with non-AD dementia. In all patients we assessed regional brain morphometry using a region of interest (ROI)-based analysis. The mean cortical thickness (CT) of 20 cortical regions and the volume (V) of 4 subcortical areas of the fronto-limbic system were extracted. NPSs were rated with the Neuropsychiatric Inventory (NPI). We used multiple linear regression models adjusted for age and disease duration to identify significant associations between scores of NPI sub-domains and MRI measures of brain morphometry. Results: All significant associations found were negative, except those between irritability and the fronto-opercular regions in MCI patients (corresponding to a 40-50% increase in CT) and between delusions and hippocampus and anterior cingulate gyrus (with a 40-60% increase). Apathy showed predominant involvement of the inferior frontal regions in AD group (a 30% decrease in CT) and of the cingulate cortex in non-AD group (a 50-60% decrease in CT). Anxiety correlated in MCI patients with the cingulate gyrus and caudate, with a CT and V decrease of about 40%, while hallucinations were associated with left enthorinal gyrus and right amygdala and temporal pole. Agitation showed associations in the AD group with the frontal regions and the temporal pole, corresponding to a 30-40% decrease in CT. Euphoria, disinhibition and eating abnormalities were associated in the MCI group with the entorhinal, para-hippocampal and fusiform gyri, the temporal pole and the amygdala (with a 40-70% decrease in CT and V). Finally, aberrant motor behavior reported a significant association with frontal and cingulate regions with a 50% decrease in CT. Conclusion: Our findings indicate that specific NPSs are associated with the structural involvement of the fronto-limbic circuit across different types of neurocognitive disorders. Factors, such as age and disease duration, can partly account for the variability of the associations observed.

20.
Zh Nevrol Psikhiatr Im S S Korsakova ; 124(4. Vyp. 2): 49-55, 2024.
Article in Russian | MEDLINE | ID: mdl-38696151

ABSTRACT

OBJECTIVE: To assess the prevalence of mild behavioral impairment (MBI ) in elderly individuals with mild cognitive impairment (MCI ), refine diagnostic criteria, and characterize the identified neuropsychiatric symptoms. MATERIAL AND METHODS: Sixty-three individuals over 50 years of age (median 72 [68; 77]) with MCI underwent psychiatric and psychometric assessments using clinical and psychopathological methods and scales. Statistical analysis was conducted to evaluate intergroup differences, ROC-analysis with calculation of the area under the curve (AUC) was performed, and sensitivity, specificity, and accuracy of MBI diagnosis were determined for MBI-C. RESULTS: The prevalence of MBI using only ISTAART research criteria was 65%. An optimal diagnostic cut point for the MBI-C scale with the highest AUC (0.793), at 10 points, was identified. Upon a comprehensive assessment of MBI using criteria and optimal cut point values from the MBI-C scale, the prevalence was 33% (median 16 [14; 20]). Patients with MBI+MCI and MCI only did not significantly differ in MMSE and MoCA test results. Significant intergroup differences were observed in the severity of symptoms such as apathy (p<0.001), depression and anxiety (p<0.001), agitation and impulsivity (p<0.001), social behavioral disturbances (p=0.009), and subsyndromal psychotic symptoms (p<0.001). The most common symptoms were related to impulse control deficits, irritability, agitation, depression, anxiety, and apathy, while less common symptoms were associated with social behavioral disturbances and subsyndromal psychotic symptoms. CONCLUSION: Novel data on the diagnostic features of MBI in elderly patients with MCI in the Russian-speaking population are presented. An optimal diagnostic cut point for the MBI-C scale in a sample of patients from specialized clinics for comprehensive use with commonly accepted criteria was determined. Further research is needed to adapt and validate the MBI-C scale and provide prognostic evaluation of MBI in the context of MCI progression to dementia.


Subject(s)
Cognitive Dysfunction , Humans , Cognitive Dysfunction/diagnosis , Female , Male , Aged , Middle Aged , Prevalence , Psychometrics , Neuropsychological Tests , Sensitivity and Specificity
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