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1.
Brain ; 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39269457

RESUMEN

The neuropsychiatric syndrome of apathy is now recognized to be a common and disabling condition in Huntington's disease (HD). However, the mechanisms underlying it are poorly understood. One way to investigate apathy is to utilise a theoretical framework of normal motivated behaviour, to determine where breakdown has occurred in people with this behavioural disruption. A fundamental computation underlying motivated, goal-directed behaviour across species is weighing up the costs and rewards associated with actions. Here, we asked whether people with apathy are more sensitive to costs of actions (physical effort and time delay), less sensitive to rewarding outcomes, or both. Based on the unique anatomical substrates associated with HD pathology, we hypothesised that a general hypersensitivity to costs would underpin HD apathy. Genetically confirmed carriers of the expanded Huntingtin gene (premanifest to mild motor manifest disease (n=53) were compared to healthy controls (n = 38). Participants performed a physical effort-based decision-making task (Apple Gathering Task) and a delay discounting task (Money Choice Questionnaire). Choice data was analysed using linear regression and drift diffusion models that also accounted for the time taken to make decisions. Apathetic people with HD accepted fewer offers overall on the Apple Gathering Task, specifically driven by increased sensitivity to physical effort costs, and not explained by motor severity, mood, cognition, or medication. Drift diffusion modelling provided further evidence of effort hypersensitivity, with apathy associated with a faster drift rate towards rejecting offers as a function of varying effort. Increased delay sensitivity was also associated with apathy, both when analysing raw choice and also drift rate, where there was moderate evidence of HD apathy drifting faster towards the immediately available (low cost) option. Furthermore, the effort and delay sensitivity parameters from these tasks were positively correlated. The results demonstrate a clear mechanism for apathy in HD, cost hypersensitivity, which manifests in both the effort and time costs associated with actions towards rewarding goals. This suggests that HD pathology may cause a domain-general disruption of cost processing, which is distinct to apathy occurrence in other brain disorders, and may require different therapeutic approaches.

2.
Artículo en Inglés | MEDLINE | ID: mdl-39288961

RESUMEN

BACKGROUND AND OBJECTIVES: Neuropsychiatric symptoms (NPS) are common in older people with cognitive impairment and Alzheimer's disease (AD). No biomarkers to detect the related pathology or predict the clinical evolution of NPS are available yet. This study aimed to identify plasma proteins that may serve as biomarkers for NPS and NPS-related clinical disease progression. METHODS: A panel of 190 plasma proteins was quantified using Luminex xMAP in the Alzheimer's Disease Neuroimaging Initiative cohort. NPS and cognitive performance were assessed at baseline and after 1 and 2 years. Logistic regression, receiver operating characteristic analysis and cross-validation were used to address the relations of interest. RESULTS: A total of 507 participants with mild cognitive impairment (n=396) or mild AD dementia (n=111) were considered. Selected plasma proteins improved the prediction of NPS (area under the curve (AUC) from 0.61 to 0.76, p<0.001) and future NPS (AUC from 0.63 to 0.80, p<0.001) when added to a reference model. Distinct protein panels were identified for single symptoms. Among the selected proteins, ANGT, CCL1 and IL3 were associated with NPS at all three time points while CCL1, serum glutamic oxaloacetic transaminase and complement factor H were also associated with cognitive decline. The associations were independent of the presence of cerebral AD pathology as assessed using cerebrospinal fluid biomarkers. CONCLUSIONS: Plasma proteins are associated with NPS and improve prediction of future NPS.

3.
J Alzheimers Dis ; 101(2): 475-485, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39240639

RESUMEN

Background: Discrepancy between caregiver and patient assessments of apathy in mild cognitive impairment (MCI) is considered an index of apathy unawareness, independently predicting progression to AD dementia. However, its neural underpinning are uninvestigated. Objective: To explore the [18F]FDG PET-based metabolic correlates of apathy unawareness measured through the discrepancy between caregiver and patient self-report, in patients diagnosed with MCI. Methods: We retrospectively studied 28 patients with an intermediate or high likelihood of MCI-AD, progressed to dementia over an average of two years, whose degree of apathy was evaluated by means of the Apathy Evaluation Scale (AES) for both patients (PT-AES) and caregivers (CG-AES). Voxel-based analysis at baseline was used to obtain distinct volumes of interest (VOIs) correlated with PT-AES, CG-AES, or their absolute difference (DISCR-AES). The resulting DISCR-AES VOI count densities were used as covariates in an inter-regional correlation analysis (IRCA) in MCI-AD patients and a group of matched healthy controls (HC). Results: DISCR-AES negatively correlated with metabolism in bilateral parahippocampal gyrus, posterior cingulate cortex, and thalamus, PT-AES score with frontal and anterior cingulate areas, while there was no significant correlation between CG-AES and brain metabolism. IRCA revealed that MCI-AD patients exhibited reduced metabolic/functional correlations of the DISCR-AES VOI with the right cingulate gyrus and its anterior projections compared to HC. Conclusions: Apathy unawareness entails early disruption of the limbic circuitry rather than the classical frontal-subcortical pathways typically associated with apathy. This reaffirms apathy unawareness as an early and independent measure in MCI-AD, marked by distinct pathophysiological alterations.


Asunto(s)
Enfermedad de Alzheimer , Apatía , Disfunción Cognitiva , Fluorodesoxiglucosa F18 , Tomografía de Emisión de Positrones , Humanos , Apatía/fisiología , Masculino , Femenino , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/psicología , Disfunción Cognitiva/metabolismo , Anciano , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/psicología , Enfermedad de Alzheimer/metabolismo , Estudios Retrospectivos , Sistema Límbico/diagnóstico por imagen , Sistema Límbico/metabolismo , Pruebas Neuropsicológicas , Anciano de 80 o más Años , Persona de Mediana Edad , Cuidadores/psicología , Concienciación/fisiología
4.
Neuropsychol Rehabil ; : 1-30, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39102382

RESUMEN

Although one of the most prevalent and impactful features of Huntington's disease (HD), little is known about the impact of apathy on HD caregivers, although there is evidence it affects perceptions of distress and burden. Given the importance of the caregivers, we aimed to explore the lived experience of people supporting someone with HD and associated apathy. Semi-structured interviews were conducted with 11 caregivers and analysed using reflective thematic analysis, informed by a phenomenological framework. Five overarching themes were produced: (1) What even is apathy? (2) It makes my life harder: the practical impact of apathy, (3) They haven't forgotten me, but they have forgotten that they ever loved me, (4) I'm grieving for someone who hasn't died yet, and (5) I need a safe space to say what I really feel without fear of judgement. Inter-woven between these themes were complex narratives about the unspoken nature of HD, the invisibility of caregivers who felt trapped and unheard, and the one-sided nature of loving someone with the disease. Findings are discussed in relation to theoretical frameworks of anticipatory grief and ambiguous loss, and situated within the wider literature on caregiving for people with a neurodegenerative condition.

5.
Artículo en Ruso | MEDLINE | ID: mdl-39113447

RESUMEN

OBJECTIVE: To evaluate the frequency and severity of various clinical symptoms of Parkinson's disease (PD) depending on the BDNF rs6265 polymorphism. MATERIAL AND METHODS: The study included 533 patients with PD. The stage of PD was assessed using the Hoehn and Yahr scale (1967), motor symptoms were evaluated with MDS-UPDRS. Assessment of non-motor symptoms (NMS) in PD was conducted using the Beck Depression Inventory II (BDI-II); the Hospital Anxiety and Depression Scale (HADS); the Apathy Scale; the Montreal Cognitive Assessment (MoCA test); the Questionnaire for Impulsive-Compulsive Disorders in PD -Rating Scale (QUIP-RS). Genotyping of the BDNF variant (rs6265) was performed using real-time PCR with TaqMan probes. RESULTS: Most PD patients have a combination of NMS increasing as the disease progresses and is determined by molecular-genetic individual characteristics. There are significant differences in the severity of motor symptoms and NMS: individuals with the AA genotype showed significantly pronounced motor symptoms (p<0.0001); emotional-affective symptoms (p<0.0001); cognitive and impulsive behavioral disorders (p<0.0001). CONCLUSION: The rs6265 BDNF allele A is associated with a wide range of NMS, increasing the risk of their development in patients with PD, thus playing the important role in the etiopathogenesis of this pathology.


Asunto(s)
Factor Neurotrófico Derivado del Encéfalo , Enfermedad de Parkinson , Polimorfismo de Nucleótido Simple , Humanos , Factor Neurotrófico Derivado del Encéfalo/genética , Enfermedad de Parkinson/genética , Femenino , Masculino , Persona de Mediana Edad , Anciano , Genotipo , Índice de Severidad de la Enfermedad , Depresión/genética
7.
Can J Nurs Res ; : 8445621241276613, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39195952

RESUMEN

BACKGROUND: In long-term care facilities (LTCF), apathy is a prevalent issue, leading to cognitive decline, functional impairment, and increased mortality risk. Despite its significance, apathy often remains underrecognized and undermanaged in these settings. Recognizing and addressing the predictors of apathy is critical for early intervention and improved care outcomes. PURPOSE: This study aims to assess the prevalence of apathy and identify its associated risk factors among newly admitted residents in the Canadian LTCF, using the InterRAI Minimum Data Set (MDS 2.0). METHODS: We conducted a cross-sectional analysis of MDS 2.0 admission assessment data between 2015 and 2019, covering 157,596 residents across six Canadian provinces and one territory. Apathy was measured using the Apathy Index of the MDS 2.0, with the biopsychosocial model guiding the analysis. RESULTS: The prevalence of apathy was 12.5% (19,758 individuals). The most significant predictors include cognitive impairments, specific age groups, hearing impairments, vision impairments, facility size and location. CONCLUSIONS: The findings of this study underscore the need for tailored strategies in LTCF to address apathy, considering individual, institutional, and regional variations. Emphasis on environmental and personal factors is crucial in the management and prevention of apathy in these settings.

8.
Aging Ment Health ; : 1-10, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39164933

RESUMEN

OBJECTIVES: This study aimed to evaluate the effects of a multicomponent psychotherapy programme for people with mild Alzheimer's dementia (AD) and their caregivers on depression and related neuropsychiatric symptoms. METHOD: The cognitive behavioural therapy (CBT)-based treatment consisted of 25 weekly sessions, including behavioural activation, behaviour management, interventions for the caregiver, reminiscence, couples counselling, and cognitive restructuring. 41 participants and their caregivers were randomised to either the CBT or the control group, which received treatment-as-usual (TAU). Follow-ups took place at 6 and 12 months posttreatment. The primary outcome was depression in the patient with AD. The secondary outcomes were apathy, other neuropsychiatric symptoms, functional abilities, quality of life, and quality of the relationship with the caregiver. RESULTS: Linear mixed models revealed a statistically significant superiority of CBT regarding clinician-rated depression at the 12-month follow-up with large effect sizes (within-subject d = 1.22, between-subject d = 1.00). Effect sizes were only moderate for self-rated depression and small for informant-rated depression. There was also a significant advantage for CBT regarding clinician-rated apathy, relationship quality, and informant-rated quality of life (QoL) but not for the other neuropsychiatric symptoms or self-rated QoL. CONCLUSION: The results are very encouraging and support an adequately powered multicentre study.Trial registration: ClinicalTrials.gov NCT01273272. Date of registration: 3 Jan 2011.

9.
Heliyon ; 10(15): e35293, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39170267

RESUMEN

Background: Parkinson's disease (PD) is associated with both sleep disturbances and apathy, and within PD, apathy has been associated with REM behavior disorder and excessive daytime sleepiness. Whether other forms of sleep disturbance are similarly associated with apathy in PD remains unclear. This study explored associations between a broad array of sleep disturbances and apathy in 50 individuals with idiopathic PD (PD) and 48 matched controls (MC). Methods: Participants were adults aged 53-80 (Mdn = 67), 23 % female, and 96 % white. Sleep disturbances were measured with various questionnaires (ISI, PSQI, PROMIS-SD, ESS, PROMIS-SRI, RBDSQ). Mood was measured with the STAI and BDI-II. Apathy was evaluated using the Apathy Scale (AS). Spearman correlations and regression analyses were performed between measures of sleep disturbance and AS in the total sample and each group. Group correlations were compared using 2-sample Fisher's z test. Results: The AS total score significantly correlated with PROMIS-SRI in the total sample and multiple measures of sleep disturbance in the PD group. The apathy subscales were each significantly correlated with sleep disturbance measures in the total sample, MC, and PD groups. The correlations between several sleep and apathy values were significantly stronger in the PD group than MC. When accounting for anxiety and depression most differences were no longer significant, only the PROMIS-SRI was significantly predictive of the behavioral apathy sub score. Discussion: Evidence supports an association between sleep disturbances and apathy in individuals with PD. Specifically, insomnia severity, poor sleep quality, and daytime sleepiness were uniquely associated with apathy in this group. We did not find these associations in the matched control group. Anxiety and depression are likely involved in the association between sleep and apathy in PD. Experimental studies that manipulate or improve sleep may further elucidate the mechanisms underlying the association between sleep disturbance and apathy in PD.

10.
Alzheimers Dement (Amst) ; 16(3): e12604, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39092182

RESUMEN

Introduction: Depression and its components significantly impact dementia prediction and severity, necessitating reliable objective measures for quantification. Methods: We investigated associations between emotion-based speech measures (valence, arousal, and dominance) during picture descriptions and depression dimensions derived from the geriatric depression scale (GDS, dysphoria, withdrawal-apathy-vigor (WAV), anxiety, hopelessness, and subjective memory complaint). Results: Higher WAV was associated with more negative valence (estimate = -0.133, p = 0.030). While interactions of apolipoprotein E (APOE) 4 status with depression dimensions on emotional valence did not reach significance, there was a trend for more negative valence with higher dysphoria in those with at least one APOE4 allele (estimate = -0.404, p = 0.0846). Associations were similar irrespective of dementia severity. Discussion: Our study underscores the potential utility of speech biomarkers in characterizing depression dimensions. In future research, using emotionally charged stimuli may enhance emotional measure elicitation. The role of APOE on the interaction of speech markers and depression dimensions warrants further exploration with greater sample sizes. Highlights: Participants reporting higher apathy used more negative words to describe a neutral picture.Those with higher dysphoria and at least one APOE4 allele also tended to use more negative words.Our results suggest the potential use of speech biomarkers in characterizing depression dimensions.

11.
Front Neurol ; 15: 1358102, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39144716

RESUMEN

Introduction: Apathy is a frequent and debilitating condition among subarachnoid hemorrhage (SAH) survivors. Few studies have evaluated apathy in SAH, and none have examined the course of the condition, predictors of persistent apathy, or its impact on functional outcomes. The proposed study will examine, for the first time, the 12-month course of apathy and its impact on functional outcomes in the largest cohort of SAH survivors to date. Methods and analysis: The current study is designed as a prospective cohort study with a duration of 36 months. We will recruit 240 participants. A trained research assistant will assess apathy using the Apathy Evaluation Scale 3 months after SAH. Patients' level of functioning, comorbidity, global cognitive functioning, and depressive symptoms will be assessed. All SAH patients will participate in follow-up assessments of apathy and functioning at 9 (T2) and 15 months (T3) post-SAH or at 6 and 12 months after the first assessment. Predictors of persistent apathy and the impact of apathy on functional outcomes will be examined. Discussion: This will be the first large-scale 1-year follow-up study of apathy in SAH survivors. The findings will provide valuable data to advance our understanding of the clinical course of apathy in this population. Moreover, the results will have clinical relevance by providing essential information to patients, caregivers, and clinicians; promoting the evaluation of apathy; and facilitating the development of prevention strategies, rehabilitation programs, and therapeutic options. Ethics and dissemination: Ethical approval for this study was obtained from the Joint Chinese University of Hong Kong-New Territories East Cluster Clinical Research Ethics Committee (CREC Ref. No.: 2023.339) on 3 October 2023. The findings of this study will be shared through publication in a peer-reviewed journal, presentations at relevant conferences, and dissemination through social media platforms.

12.
J Neuromuscul Dis ; 11(5): 1123-1130, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39093078

RESUMEN

Background: Chronic respiratory failure often occurs in myotonic dystrophy type 1 (DM1) and can be treated with noninvasive home mechanical ventilation (HMV). Treatment adherence with HMV is often suboptimal in patients with DM1, but the reasons for that are not well understood. Objective: The aim of this exploratory study was to gain insight in the prevalence of mild cognitive impairment, affective symptoms, and apathy and to investigate their role in HMV treatment adherence in DM1. Methods: The Montreal Cognitive Assessment (MoCA), the Hospital Anxiety and Depression Scale (HADS), and the Apathy Evaluation Scale (AES) were used to assess cognition, affective symptoms, and apathy in DM1 patients that use HMV. Patients with low treatment adherence (average daily use HMV <5 h or <80% of the days) were compared with patients with high treatment adherence (average daily use of HMV≥5 h and ≥80% of the days). Results: Sixty patients were included. Abnormal scores were found in 40% of the total group for the MoCA, in 72-77% for the AES, and in 18% for HADS depression. There was no difference between the high treatment adherence group (n = 39) and the low treatment adherence group (n = 21) for the MoCA, AES, and HADS depression. The HADS anxiety was abnormal in 30% of the total group, and was significantly higher in the low treatment adherence group (p = 0.012). Logistic regression analysis revealed that a higher age and a higher BMI were associated with a greater chance of high treatment adherence. Conclusions: This exploratory study showed that cognitive impairment and apathy are frequently present in DM1 patients that use HMV, but they are not associated with treatment adherence. Feelings of anxiety were associated with low treatment adherence. Higher age and higher BMI were associated with high treatment adherence with HMV.


Asunto(s)
Apatía , Disfunción Cognitiva , Distrofia Miotónica , Humanos , Distrofia Miotónica/psicología , Distrofia Miotónica/terapia , Distrofia Miotónica/complicaciones , Masculino , Femenino , Persona de Mediana Edad , Adulto , Disfunción Cognitiva/etiología , Disfunción Cognitiva/terapia , Síntomas Afectivos/etiología , Síntomas Afectivos/terapia , Ventilación no Invasiva , Cumplimiento y Adherencia al Tratamiento/estadística & datos numéricos , Servicios de Atención de Salud a Domicilio , Anciano , Insuficiencia Respiratoria/terapia , Insuficiencia Respiratoria/etiología , Insuficiencia Respiratoria/psicología , Cognición
13.
J Am Med Dir Assoc ; 25(10): 105193, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39117299

RESUMEN

OBJECTIVES: This study evaluated the factorial structure, psychometric properties, and diagnostic accuracy of the Persian version of the Lille Apathy Rating Scale-Patient version (LARS-P) in stroke survivors. PARTICIPANTS: This study comprised 105 stroke survivors and 41 healthy controls. METHODS AND SETTING: Exploratory factor analysis was used to determine the factors of the LARS-P. The acceptability, reliability, and validity of the LARS-P were also assessed. Agreement between the LARS-P and the Lille Apathy Rating Scale-informed version (LARS-I) was evaluated using the Bland-Altman plot. The diagnostic accuracy of the LARS-P was determined by categorizing stroke survivors into apathetic and nonapathetic groups based on the "diagnostic criteria of apathy." RESULTS: The exploratory factor analysis showed 3 factors (action initiation and social life; novelty and motivation; and emotional and self-awareness), explaining 67.35% of the variance. Cronbach's alpha was 0.85 for between-items and 0.74 for between-subscales. Intra-class correlation coefficient (ICC)2,1 was >0.88 for test-retest and inter-rater reliability. The LARS-P showed moderate to strong correlations with the LARS-I and Neuropsychiatric Inventory-Apathy subscale (r = 0.70-0.82). In addition, the LARS-P had significant moderate correlations with 2 subscales of the Hospital Anxiety and Depression Scale, modified Rankin Scale, Barthel Index, and Lawton Instrumental Activities of Daily Living (r or Æ¿ = 0.47-0.63). There was a 96.19% agreement between LARS-P and LARS-I. The identified cutoff point (>17) for LARS-P exhibited 77.14% sensitivity and 90% specificity in diagnosing apathetic and nonapathetic stroke survivors. CONCLUSIONS AND IMPLICATIONS: The LARS-P exhibits acceptable psychometric properties in stroke survivors, presenting a promising instrument for assessing apathy through a multidimensional framework.

14.
Clin Gerontol ; : 1-9, 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39046886

RESUMEN

OBJECTIVES: The questionnaire Apathy Evaluation Scale-Self (AES-S) has been widely adopted globally, demonstrating high reliability and validity. However, direct translation of the AES into Chinese does not fit well into the Chinese cultural setting, so a structured and comprehensive revision is needed to obtain a high reliability and validity version of the scale. METHODS: In this study, 436 adults aged ≥ 60 years from two communities in Beijing were assessed using a modified AES-S. The methodology included item analysis, exploratory factor analysis, and confirmatory factor analysis. The scale's validity was tested using the Temporal Experience of Pleasure Scale (TEPS) and Mini-Mental State Examination (MMSE). Reliability assessment included retest reliability, internal consistency reliability, and split-half reliability. RESULTS: The modified Apathy Evaluation Scale-Self-Assessment (AES-S-C) presented a first-order four-factor structure with higher reliability and validity than the original version within the Chinese older adult community. CONCLUSIONS: The revised AES-S-C is more suitable for the Chinese older adults in community settings. CLINICAL IMPLICATIONS: This self-rated scale is suitable for screening apathy among older adults in community or nursing facilities, aiding in the identification of cognitive impairment and promoting mental health.

15.
J Alzheimers Dis ; 100(s1): S57-S61, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39031368

RESUMEN

Social dysfunction is a maladaptive process of coping, problem solving, and achieving one's goals. A new definition of apathy was cross-linked to social dysfunction, with a reduced goal-directed behavior and social interaction as a separate dimension. We hypothesized that these two neuropsychiatric symptoms may be included in the mild behavioral impairment diagnostic framework, operationalizing and standardizing late-life neuropsychiatric symptom assessment, to improve risk determination of dementia. Social dysfunction and apathy were transdiagnostic and prodromic for late-life cognitive disorders. A transdiagnostic approach could provide a useful mean for a better understanding of apathy and related conditions such as social behavior.


Asunto(s)
Apatía , Disfunción Cognitiva , Conducta Social , Anciano , Humanos , Apatía/fisiología , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/psicología , Pruebas Neuropsicológicas , Envejecimiento Cognitivo/fisiología
16.
Pers Soc Psychol Bull ; : 1461672241265993, 2024 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-39066671

RESUMEN

More than 5,000 Native American and Alaska Native women and girls go missing annually in the United States, and murder is the third leading cause of death for those aged 10 to 24. The current studies assess why, despite such statistics, individuals who are not Native American fail to advocate for Missing and Murdered Indigenous Women and Girls (MMIWG). The Pilot Study (N = 205) and Study 1 (N = 3,992) revealed that greater cognitive invisibility of contemporary Native Peoples (i.e., the absence of cognitive representations) was related to greater minimization of Native Peoples' experiences with racism. Racism minimization was associated with greater blaming of MMIWG victims and less blaming of societal contributors to the epidemic. These factors predicted greater apathy toward MMIWG and less MMIWG advocacy. The results suggest that the cognitive invisibility of Native Peoples affords attitudes and beliefs that allow non-Native individuals to deny, justify, and distance themselves from the MMIWG epidemic.

17.
Int J Mol Sci ; 25(14)2024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-39063235

RESUMEN

Among the symptoms of Parkinson's disease (PD), apathy comprises a set of behavioral, affective, and cognitive features that can be classified into several subtypes. However, the pathophysiology and brain regions that are involved in these different apathy subtypes are still poorly characterized. We examined which subtype of apathy is elicited in a mouse model of PD with 6-hydroxydopamine (6-OHDA) lesions and the behavioral symptoms that are exhibited. Male C57/BL6J mice were allocated to sham (n = 8) and 6-OHDA (n = 13) groups and locally injected with saline or 4 µg 6-OHDA bilaterally in the dorsal striatum. We then conducted motor performance tests and apathy-related behavioral experiments. We then pathologically evaluated tyrosine hydroxylase (TH) immunostaining. The 6-OHDA group exhibited significant impairments in motor function. In the behavioral tests of apathy, significant differences were observed between the sham and 6-OHDA groups in the hole-board test and novelty-suppressed feeding test. The 6-OHDA group exhibited impairments in inanimate novel object preference, whereas social preference was maintained in the three-chamber test. The number of TH+ pixels in the caudate putamen and substantia nigra compacta was significantly reduced in the 6-OHDA group. The present mouse model of PD predominantly showed dorsal striatum dopaminergic neuronal loss and a decrease in novelty seeking as a symptom that is related to the cognitive apathy component.


Asunto(s)
Apatía , Conducta Animal , Cuerpo Estriado , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Oxidopamina , Enfermedad de Parkinson , Animales , Oxidopamina/farmacología , Oxidopamina/efectos adversos , Apatía/efectos de los fármacos , Masculino , Ratones , Cuerpo Estriado/efectos de los fármacos , Cuerpo Estriado/patología , Cuerpo Estriado/metabolismo , Enfermedad de Parkinson/patología , Enfermedad de Parkinson/fisiopatología , Conducta Animal/efectos de los fármacos , Cognición/efectos de los fármacos , Tirosina 3-Monooxigenasa/metabolismo , Actividad Motora/efectos de los fármacos
18.
Artículo en Inglés | MEDLINE | ID: mdl-39013750

RESUMEN

OBJECTIVE: Understanding the course of individual neuropsychiatric symptoms (NPS) and their relationship with function is important for planning targeted interventions for preventing and delaying functional decline. This study aims to disentangle relative contributions of individual NPS on functional decline. METHODS: Longitudinal study of 9,358 well-characterized participants with baseline diagnoses of Mild Cognitive Impairment or AD in the National Alzheimer's Coordinating Center Uniform Data Set. Function was measured using the Functional Assessment Questionnaire (FAQ). Clinician judgment of seven common behavioral symptoms were examined simultaneously: apathy-withdrawal, depressed mood, visual or auditory hallucinations, delusions, disinhibition, irritability, and agitation. RESULTS: Apathy was the most common NPS at baseline (33.7%) and throughout follow-up, endorsed by clinicians in 63.7% of visits. Apathy was the most persistent with 36.7% of participants having clinician-endorsed apathy in ≥50% of their visits. Apathy strongly correlated with faster rate of functional decline. Compared to those who never had apathy, baseline FAQ was worse in those with intermittent or persistent/always apathy (intermittent: estimated coefficient ±SE=1.228±0.210, 95% CI=[0.817, 1.639]; persistent/always: 2.354±0.244 (95% CI=[1.876, 2.832], both p <0.001). Over time, rate of functional decline was faster in those with intermittent and persistent/always apathy (intermittent: 0.454±0.091, 95% CI=[0.276, 0.632]; persistent/always: 0.635±0.102, 95% CI=[0.436, 0.835], both p <0.001). Worse agitation, delusions, and hallucinations also correlated with functional decline, but magnitudes of the estimates were smaller. CONCLUSION: Individual NPS may be sensitive targets for tracking longitudinal change in function. The study raises awareness of the need for more comprehensive assessment of functional decline in AD patients with noncognitive symptoms.

19.
Quant Imaging Med Surg ; 14(7): 4735-4748, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-39022244

RESUMEN

Background: Apathy, characterized by diminished goal-directed behaviors, frequently occurs in patients with Parkinson's disease (PD). The dopamine-releasing neurons of the ventral tegmental area (VTA) have been closely related to this behavioral disruption and project widely to the corticolimbic areas, yet their functional and structural connectivity in regard to other brain regions remain unknown in patients with PD and pure apathy (PD-PA). This study thus aimed to characterize the alterations of functional connectivity (FC) of the VTA and white matter structural connectivity in PD-PA. Methods: In this study, 29 patients with PD-PA, 37 with PD but not pure apathy (PD-NPA), and 28 matched healthy controls (HCs) underwent T1-weighted, resting state functional magnetic resonance imaging, and diffusion tensor imaging scans. Patients of this cross-sectional retrospective study were consecutively recruited from The First Affiliated Hospital of Nanjing Medical University between April 2017 and October 2021. Meanwhile, HCs were consecutively recruited from the local community and the Health Examination Center of our hospital. An analysis of covariance and a general linear model were respectively conducted to investigate the functional and structural connectivity among three groups. The tract-based spatial statistics (TBSS) approach was used to investigate the white matter structural connectivity. Results: Patients with PD-PA showed reduced FC of the VTA with the left medial superior frontal gyrus (SFGmed) when compared to the patients with PD-NPA [t=-3.67; voxel-level P<0.001; cluster-level family-wise error-corrected P (PFWE)<0.05]. Relative to the HCs, patients with PD-PA demonstrated reduced FC of the VTA with the left SFGmed (t=-4.98; voxel-level P<0.001; cluster-level PFWE<0.05), right orbital superior frontal gyrus (SFGorb) (t=-5.08; voxel-level P<0.001; cluster-level PFWE<0.05), and right middle frontal gyrus (MFG) (t=-5.08; voxel-level P<0.001; cluster-level PFWE<0.05). Moreover, the reductions in VTA FC with the left SFGmed were associated with severe apathy symptoms in patients with PD-PA (r=-0.600; P=0.003). However, a TBSS approach did not reveal any significant differences in fiber tracts between the three groups. Conclusions: This study identified reduced FC within the mesocortical network (VTA-SFGmed) of patients with PD-PA. These findings may provide valuable information for administering neuromodulation therapies in the alleviation of apathy symptoms in those with PD.

20.
Front Public Health ; 12: 1395939, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39076422

RESUMEN

Introduction: Lassa fever is a zoonotic infectious disease endemic in West Africa with a high case-fatality rate and reported stigmatization of surviving patients. This study examines discrimination among survivors of Lassa fever (LF) complicated by hearing loss (HL). Methods: This cross-sectional qualitative study used an in-depth interview guide to collect information from patients with HL about their experience of stigma. Interviews were conducted by a trained team of interviewers at the Jos University Teaching Hospital between January and April 2022 in Hausa language after informed consent was obtained. Recordings of the interviews were transcribed and translated from Hausa to English. Data analysis was conducted using NVivo software using a thematic framework approach. Results: Most (73%) respondents were male (n = 11); 27% were female (n = 4). The median age was 35 years (interquartile range, 16.5). Some Lassa fever patients experienced stigma and discrimination (53%) including isolation and withdrawal of family and community support during and after illness. HL increased stigma, as some patients were labeled "deaf" by other community members, increasing perceived stigma and devaluation. HL affected the socio-economic wellbeing of some who could not communicate well with their families and customers and constrained social interactions, evoking pain and apathy. Some survivors of LF and victims of its sequelae of HL experienced double stigmatization. While they were ill with LF, a third of respondents reported avoidance and isolation by family and community members who withdrew care and support both to them and their close family members. These forms of stigmatization strained their relationships. Conclusion: There is a need to address stigma in LF survivors who develop HL through concerted community-owned awareness to improve their quality of life along with a robust social support system to aid prevention.


Asunto(s)
Pérdida Auditiva , Fiebre de Lassa , Investigación Cualitativa , Estigma Social , Humanos , Estudios Transversales , Nigeria , Femenino , Masculino , Fiebre de Lassa/psicología , Adulto , Persona de Mediana Edad , Pérdida Auditiva/psicología , Adulto Joven , Entrevistas como Asunto , Adolescente
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