Amidst an amygdala renaissance in Alzheimer's disease.

The amygdala was highlighted as an early site for neurofibrillary tau tangle pathology in Alzheimer's disease in the seminal 1991 article by Braak and Braak. This knowledge has, however, only received traction recently with advances in imaging and image analysis techniques. Here, we provide a cross-disciplinary overview of pathology and neuroimaging studies on the amygdala. These studies provide strong support for an early role of the amygdala in Alzheimer's disease and the utility of imaging biomarkers of the amygdala in detecting early changes and predicting decline in cognitive functions and neuropsychiatric symptoms in early stages. We summarize the animal literature on connectivity of the amygdala, demonstrating that amygdala nuclei that show the earliest and strongest accumulation of neurofibrillary tangle pathology are those that are connected to brain regions that also show early neurofibrillary tangle accumulation. Additionally, we propose an alternative pathway of neurofibrillary tangle spreading within the medial temporal lobe between the amygdala and the anterior hippocampus. The proposed existence of this pathway is strengthened by novel experimental data on human functional connectivity. Finally, we summarize the functional roles of the amygdala, highlighting the correspondence between neurofibrillary tangle accumulation and symptomatic profiles in Alzheimer's disease. In summary, these findings provide a new impetus for studying the amygdala in Alzheimer's disease and a unique perspective to guide further study on neurofibrillary tangle spreading and the occurrence of neuropsychiatric symptoms in Alzheimer's disease.

Severe steroid-related neuropsychiatric symptoms during paediatric acute lymphoblastic leukaemia therapy-An observational Ponte di Legno Toxicity Working Group Study.

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.

Neuropsychiatric symptoms: Risk factor or disease marker? A study of structural imaging biomarkers of Alzheimer's disease and incident cognitive decline.

Neuropsychiatric symptoms (NPS) are risk factors for Alzheimer's disease (AD) but can also manifest secondary to AD pathology. Mild behavioral impairment (MBI) refers to later-life emergent and persistent NPS that may mark early-stage AD. To distinguish MBI from NPS that are transient or which represent psychiatric conditions (non-MBI NPS), we investigated the effect of applying MBI criteria on NPS associations with AD structural imaging biomarkers and incident cognitive decline. Data for participants (n = 1273) with normal cognition (NC) or mild cognitive impairment (MCI) in the National Alzheimer's Coordinating Center Uniform Data Set were analyzed. NPS status (MBI, non-MBI NPS) was derived from the Neuropsychiatric Inventory Questionnaire and psychiatric history. Normalized measures of bilateral hippocampal (HPC) and entorhinal cortex (EC) volume, and AD meta-region of interest (ROI) mean cortical thickness were acquired from T1-weighted magnetic resonance imaging scans. Multivariable linear and Cox regressions examined NPS associations with imaging biomarkers and incident cognitive decline, respectively. MBI was associated with lower volume and cortical thickness in all ROIs in both NC and MCI, except for EC volume in NC. Non-MBI NPS were only associated with lower HPC volume in NC. Although both of the NPS groups showed higher hazards for MCI/dementia than No NPS, MBI participants showed more rapid decline. Although both types of NPS were linked to HPC atrophy, only NPS that emerged and persisted in later-life, consistent with MBI criteria, were related to AD neurodegenerative patterns beyond the HPC. Moreover, MBI predicted faster progression to dementia than non-MBI NPS.

Inflammatory biomarkers for neurobehavioral dysregulation in former American football players: findings from the DIAGNOSE CTE Research Project.

BACKGROUND: Traumatic encephalopathy syndrome (TES) is defined as the clinical manifestation of the neuropathological entity chronic traumatic encephalopathy (CTE). A core feature of TES is neurobehavioral dysregulation (NBD), a neuropsychiatric syndrome in repetitive head impact (RHI)-exposed individuals, characterized by a poor regulation of emotions/behavior. To discover biological correlates for NBD, we investigated the association between biomarkers of inflammation (interleukin (IL)-1ß, IL-6, IL-8, IL-10, C-reactive protein (CRP), tumor necrosis factor (TNF)-α) in cerebrospinal fluid (CSF) and NBD symptoms in former American football players and unexposed individuals. METHODS: Our cohort consisted of former American football players, with (n = 104) or without (n = 76) NBD diagnosis, as well as asymptomatic unexposed individuals (n = 55) from the DIAGNOSE CTE Research Project. Specific measures for NBD were derived (i.e., explosivity, emotional dyscontrol, impulsivity, affective lability, and a total NBD score) from a factor analysis of multiple self-report neuropsychiatric measures. Analyses of covariance tested differences in biomarker concentrations between the three groups. Within former football players, multivariable linear regression models assessed relationships among log-transformed inflammatory biomarkers, proxies for RHI exposure (total years of football, cumulative head impact index), and NBD factor scores, adjusted for relevant confounding variables. Sensitivity analyses tested (1) differences in age subgroups (< 60, ≥ 60 years); (2) whether associations could be identified with plasma inflammatory biomarkers; (3) associations between neurodegeneration and NBD, using plasma neurofilament light (NfL) chain protein; and (4) associations between biomarkers and cognitive performance to explore broader clinical symptoms related to TES. RESULTS: CSF IL-6 was higher in former American football players with NBD diagnosis compared to players without NBD. Furthermore, elevated levels of CSF IL-6 were significantly associated with higher emotional dyscontrol, affective lability, impulsivity, and total NBD scores. In older football players, plasma NfL was associated with higher emotional dyscontrol and impulsivity, but also with worse executive function and processing speed. Proxies for RHI exposure were not significantly associated with biomarker concentrations. CONCLUSION: Specific NBD symptoms in former American football players may result from multiple factors, including neuroinflammation and neurodegeneration. Future studies need to unravel the exact link between NBD and RHI exposure, including the role of other pathophysiological pathways.

Clinical and diagnostic features of long-COVID patients presenting with neurologic symptoms in Chicago.

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.

Emerging therapies for treatment of agitation, psychosis, or apathy in Alzheimer's disease.

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.

The Relationship Between First Presenting Neuropsychiatric Symptoms in Older Adults and Autopsy-Confirmed Memory Disorders.

OBJECTIVES: Although dementia is typically considered a disease of cognitive decline, almost all patients present with neuropsychiatric symptoms (NPS) at some stage of their disease. Few studies have assessed the timing of NPS onset in relation to pathological diagnoses of neurodegenerative diseases. We sought to examine the association between the first presenting clinically significant NPS in aging individuals and neuropathological diagnoses of memory disorders. DESIGN: This retrospective longitudinal cohort study utilized the National Alzheimer's Coordinating Center (NACC) dataset, which includes participant data from 37 Alzheimer's Disease Research Centers collected between 2005 and 2022. PARTICIPANTS: Participants (N = 5,416) aged 45 years or older with Clinical Dementia Rating-Global ratings of less than or equal to 1 were included in this analysis. A total of 4,033 (74.5%) participants presented with at least one NPS at any NACC visit. MEASUREMENTS: To measure first NPS, the NACCBEHF variable was used, a clinician-rated variable defined as "the predominant symptom that was first recognized as a decline in the subject's behavior." Neuropathologic variables included assessments of Alzheimer's Disease, Frontotemporal Dementia, Lewy Body Dementia, Cerebral Amyloid Angiopathy, Hippocampal Sclerosis, and Cerebrovascular Disease. RESULTS: Presentation with any clinically significant first NPS was associated with several neuropathological diagnoses including Alzheimer's Disease, Frontotemporal Lobar Dementia with TDP-43 pathology, and Lewy Body Dementia. While specific first NPS were associated with Frontotemporal Dementia neuropathology (personality change and disinhibition) and Lewy Body Dementia neuropathology (psychosis and REM behavior disturbance), Alzheimer's Disease neuropathology was associated with the majority of NPS. CONCLUSIONS: Since neuropsychiatric symptoms are frequently the first presenting symptom of dementia, their associations with well-defined neuropathological diagnoses may help clinicians predict the subtype of future dementias.

Demographics, Symptoms, Psychotropic Use, and Caregiver Distress in Patients With Early vs Late Onset Dementia.

BACKGROUND: Understanding experiences and challenges faced by persons living with Early-Onset Dementia (EOD) compared to individuals diagnosed with Late-Onset Dementia (LOD) is important for the development of targeted interventions. OBJECTIVE: Describe differences in sociodemographic, neuropsychiatric behavioral symptoms, caregiver characteristics, and psychotropic use. DESIGN, SETTING, PARTICIPANTS: Cross-sectional, retrospective study including 908 UCLA Alzheimer's Dementia Care Program participants (177 with EOD and 731 with LOD). MEASUREMENTS: Onset of dementia was determined using age at program enrollment, with EOD defined as age <65 years and LOD defined as age >80 years. Sociodemographic and clinical characteristics were measured once at enrollment. Behavioral symptoms were measured using the Neuropsychiatric Inventory Questionnaire (NPI-Q) severity score and caregiver distress was measured using the NPI-Q distress score. Medications included antipsychotic, antidepressant, benzodiazepines and other hypnotics, antiepileptics, and dementia medications. RESULTS: EOD compared to LOD participants were more likely men, college graduates, married, live alone, and have fewer comorbidities. EOD caregivers were more often spouses (56% vs 26%, p <0.01), whereas LOD caregivers were more often children (57% vs 10%, p <0.01). EOD was associated with lower odds of being above the median (worse) NPI-Q severity (adjusted odds ratio [aOR], 0.58; 95% CI 0.35-0.96) and NPI-Q distress scores (aOR, 0.53; 95% CI 0.31-0.88). Psychotropic use did not differ between groups though symptoms were greater for LOD compared to EOD. CONCLUSION: Persons with EOD compared to LOD had sociodemographic differences, less health conditions, and fewer neuropsychiatric symptoms. Future policies could prioritize counseling for EOD patients and families, along with programs to support spousal caregivers of persons with EOD.

Neuropsychiatric Symptom Profile in Alzheimer's Disease and Their Relationship With Functional Decline.

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.

Identifying and Diagnosing TDP-43 Neurodegenerative Diseases in Psychiatry.

Neuropsychiatric symptoms (NPS) are common manifestations of neurodegenerative disorders and are often early signs of those diseases. Among those neurodegenerative diseases, TDP-43 proteinopathies are an increasingly recognized cause of early neuropsychiatric manifestations. TDP-43-related diseases include frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), and Limbic-Predominant Age-Related TDP-43 Encephalopathy (LATE). The majority of TDP-43-related diseases are sporadic, but a significant proportion is hereditary, with progranulin (GRN) mutations and C9orf72 repeat expansions as the most common genetic etiologies. Studies reveal that NPS can be the initial manifestation of those diseases or can complicate disease course, but there is a lack of awareness among clinicians about TDP-43-related diseases, which leads to common diagnostic mistakes or delays. There is also emerging evidence that TDP-43 accumulations could play a role in late-onset primary psychiatric disorders. In the absence of robust biomarkers for TDP-43, the diagnosis remains primarily based on clinical assessment and neuroimaging. Given the association with psychiatric symptoms, clinical psychiatrists have a key role in the early identification of patients with TDP-43-related diseases. This narrative review provides a comprehensive overview of the pathobiology of TDP-43, resulting clinical presentations, and associated neuropsychiatric manifestations to help guide clinical practice.

Compassionate mind training for people with Parkinson's disease: A pilot study and predictors of response.

INTRODUCTION: People with Parkinson's disease (PD) often present with disabling neuropsychiatric symptoms. Compassionate mind training (CMT) is a psychological approach effective in reducing stress and promoting psychological well-being. Heart rate variability (HRV), a measure reflecting sympathovagal balance, has been associated with psychological well-being and a compassionate attitude. AIM: To assess the feasibility and effectiveness of CMT in enhancing the quality of life and psychological well-being in PD patients. Additionally, we evaluated HRV as a physiomarker for assessing the CMT outcomes. METHODS: Twenty-four PD patients participated in the study. A 6-week online CMT intervention was delivered on a weekly basis. At baseline and post-intervention patients completed questionnaires assessing depression, anxiety and quality of life. In a subsample of 11 patients, HRV was measured at baseline and post-intervention in three conditions: at rest, during stress and after 3 min of deep breathing. RESULTS: The attendance rate was 94.3%. Quality of life and perceived stigma improved post-intervention as compared with baseline (p = 0.02 and p = 0.03 for PD Questionnaire-39 total score and Stigma subscore, respectively). After CMT, patients presented better physiological regulation to stress, as measured by higher HRV as compared with baseline (p = 0.005). Notably, patients who were more resilient to stress at baseline (less decrease in HRV during stress) experienced a more substantial reduction in anxiety and depression following CMT. CONCLUSIONS: CMT is feasible and can improve quality of life and stigma in PD patients. HRV emerges as a promising physiomarker for predicting and measuring the outcomes of psychological interventions in PD.

Trajectories of behavior and social cognition in behavioral variant frontotemporal dementia and primary psychiatric disorders: A call for better operationalization of socioemotional changes.

BACKGROUND AND PURPOSE: Behavioral variant frontotemporal dementia (bvFTD) and primary psychiatric disorders (PPD), such as mood, psychotic, and autism spectrum disorders, share similar clinical characteristics of behavior and social cognition. Better understanding of clinical progression in bvFTD and PPD is essential for adequate disease monitoring and trial design. METHODS: In this longitudinal study (N = 89), patients with bvFTD and PPD with at least one follow-up assessment were included from the Social Brain Project of the Alzheimer Center Amsterdam. Behavioral change and social cognitive decline were assessed via informant-rated questionnaires (Cambridge Behavioral Inventory-Revised, Frontal Behavioral Inventory [FBI], Stereotypy Rating Inventory, Frontotemporal Dementia Rating Scale, Revised Self-Monitoring Scale [RSMS]-caregiver) and patient assessment (Ekman 60-Faces Test, RSMS-patient, Emotional Contagion Scale). Clinical trajectories (median = 1.4 years, interquartile range = 1.0-2.2) were examined using linear mixed models. In a subsample, associations with baseline serum neurofilament light (sNfL) were examined. RESULTS: At baseline, behavioral and social cognitive symptoms were similar between diagnosis groups, except for poorer emotion recognition in bvFTD. Over time, behavioral symptoms worsened in bvFTD, whereas most measures remained stable and the FBI improved in PPD. Regarding social cognition, emotion recognition and caregiver-reported socioemotional sensitivity worsened in bvFTD and remained stable in PPD. Patient-reported social cognitive measures did not change over time. Higher sNfL was associated with faster behavioral change. CONCLUSIONS: Trajectories of behavior and social cognition differentiate bvFTD from PPD, provided that social cognition is not patient-reported. Therefore, we stress the need to optimize longitudinal social cognitive assessment in bvFTD. sNfL may be a useful prognostic marker of behavioral progression in neuropsychiatric populations.

Neuropsychiatric Profiles and Cerebral Amyloid Burden in Adults without Dementia.

INTRODUCTION: We comprehensively evaluated how self- and informant-reported neuropsychiatric symptoms (NPS) were differentially associated with cerebral amyloid-beta (Aß) PET levels in older adults without dementia. METHODS: Two hundred and twenty-one participants (48% female, age = 73.4 years ± 8.4, Clinical Dementia Rating = 0 [n = 184] or 0.5 [n = 37]) underwent an Aß-PET scan (florbetapir or PIB), comprehensive neuropsychological testing, and self-reported (Geriatric Depression Scale - 30 item [GDS-30]) and informant-reported interview (Neuropsychiatric Inventory Questionnaire [NPI-Q]) of NPS. Cerebral Aß burden was quantified using centiloids (CL). NPI-Q and GDS-30 queried the presence of NPS within 4 subdomains and 6 subscales, respectively. Regression models examined the relationship between NPS and Aß-PET CL. RESULTS: Both higher self- and informant-reported NPS were associated with higher Aß burden. Among specific NPI-Q subdomains, informant-reported changes in depression, anxiety, and irritability were all associated with higher Aß-PET. Similarly, self-reported (GDS-30) subscales of depression, apathy, anxiety, and cognitive concern were associated with higher Aß-PET. When simultaneously entered, only self-reported cognitive concern was associated with Aß-PET in the GDS-30 model, while both informant-reported anxiety and depression were associated with Aß-PET in the NPI-Q model. Clinical status moderated the association between self-reported NPS and Aß-PET such that the positive relationship between self-perceived NPS and Aß burden strengthened with increasing functional difficulties. CONCLUSIONS: In a cohort of older adults without dementia, both self- and informant-reported measures of global NPS, particularly patient-reported cognitive concerns and informant-reported anxiety and depression, corresponded with cerebral Aß burden. NPS may appear early in the prodromal disease state and relate to initial AD proteinopathy burden, a relationship further exaggerated in those with greater clinical severity.

Neuroanatomical and neurocognitive correlates of delusion in Alzheimer's disease and mild cognitive impairment.

BACKGROUND: Neuropsychiatric symptoms and delusions are highly prevalent among people with dementia. However, multiple roots of neurobiological bases and shared neural basis of delusion and cognitive function remain to be characterized. By utilizing a fine-grained multivariable approach, we investigated distinct neuroanatomical correlates of delusion symptoms across a large population of dementing illnesses. METHODS: In this study, 750 older adults with mild cognitive impairment and Alzheimer's disease completed brain structural imaging and neuropsychological assessment. We utilized principal component analysis followed by varimax rotation to identify the distinct multivariate correlates of cortical thinning patterns. Five of the cognitive domains were assessed whether the general cognitive abilities mediate the association between cortical thickness and delusion. RESULTS: The result showed that distributed thickness patterns of temporal and ventral insular cortex (component 2), inferior and lateral prefrontal cortex (component 1), and somatosensory-visual cortex (component 5) showed negative correlations with delusions. Subsequent mediation analysis showed that component 1 and 2, which comprises inferior frontal, anterior insula, and superior temporal regional thickness accounted for delusion largely through lower cognitive functions. Specifically, executive control function assessed with the Trail Making Test mediated the relationship between two cortical thickness patterns and delusions. DISCUSSION: Our findings suggest that multiple distinct subsets of brain regions underlie the delusions among older adults with cognitive impairment. Moreover, a neural loss may affect the occurrence of delusion in dementia largely due to impaired general cognitive abilities.

Emotion Regulation in Dementia Caregiving: The Role of Neuropsychiatric Symptoms and Attachment Orientation.

Family caregivers are usually the main source of support for persons living with dementia, being exposed to a loved one's suffering, which can lead to experiencing strong and negative emotions. This study aimed to identify factors capable of explaining individual differences in the way caregivers regulate their emotions. This cross-sectional study included 78 informal caregivers (M = 64.84 years; SD = 13.32) and 84 controls (non-caregivers) (M = 77 years; SD = 7.59). Neuropsychiatric symptoms (NPS), attachment orientations, and emotion regulation were measured using self-report scales. Caregivers of persons living with dementia used more expressive suppression in comparison to non-caregivers. NPS and attachment avoidance were associated with expressive suppression. Moderation analyses showed that NPS only predicted expressive suppression when attachment avoidance was low or medium. The present study showed that caregivers are more likely to suppress their emotions in the presence of NPS, especially those with lower/middle levels of attachment avoidance. Psychological interventions targeting emotion regulation should be offered especially to caregivers that face NPS of persons living with dementia and present lower/middle levels of attachment avoidance.

Neuropsychiatric Comorbidities and Psychotropic Medication Use in Medicare Beneficiaries With Dementia by Sex and Race.

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.

Treatment of Neuropsychiatric Symptoms in Parkinson's Disease With Botulinum Toxin A: A 12 week Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVE: The study aimed to evaluate the impact of Botulinum toxin A (BoNT/A) on neuropsychiatric symptoms in Parkinson's disease (PD) patients. METHODS: A total of 125 PD patients and an equal number of age- and gender-matched healthy controls were involved. Mental health status was assessed using the Cornell Medical Index (CMI) self-assessment questionnaire. Sixty-four PD patients exhibiting neuropsychiatric symptoms were selected for the controlled study and randomly grouped into treatment and control groups. The treatment group received BoNT/A injections, while the control group received a placebo. The primary outcome measures included depression scores from the CMI and the proportion of patients displaying improvement in neuropsychiatric symptoms at 8 weeks post-treatment. The secondary outcome was other CMI scores at 4, 8, and 12 weeks post-treatment. RESULTS: The outcomes revealed that PD patients had significantly higher scores in various neuropsychiatric factors compared to healthy controls. At 4 weeks post-treatment, the treatment group displayed improvements in depression and tension. At 8 weeks post-treatment, they exhibited significant reductions in depression, anxiety, sensitivity, and tension compared to the control group. Moreover, a notably higher percentage of patients in the treatment group showed improvement in neuropsychiatric symptoms compared to the control group. At 12 weeks post-treatment, the treatment group exhibited significant improvements in somatization, depression, sensitivity, and tension. CONCLUSION: PD patients commonly experience multiple neuropsychiatric symptoms, and BoNT/A has demonstrated efficacy in alleviating these symptoms. Specifically, BoNT/A was found to effectively alleviate somatization, tension, anxiety, depression, and sensitivity in PD patients.

Validity and Reliability of the Turkish Version of Mild Behavioral Impairment Checklist in Patients With Cognitive Impairment.

BACKGROUND AND OBJECTIVE: The Mild Behavioral Impairment-Checklist (MBI-C) was developed to detect and standardize neuropsychiatric symptoms. The objective of this study was to evaluate the Turkish adaptation, validity, and reliability of the MBI-C. METHODS: The sample of our study consisted of 80 patients with cognitive impairment and a control group with 113 participants whose cognitive impairment was not detected in standard tests. Participants were evaluated with the Standardized Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Geriatric Depression Scale-15 (GDS-15), MBI-C and Neuropsychiatric Inventory (NPI). RESULTS AND CONCLUSION: In the reliability analysis, the Cronbach-alpha value for MBI-C was found to be .810. In the ROC analysis performed with the total MBI-C score, the area under the curve (AUC) was calculated as .821 and the cut-off score was determined as 8.5; sensitivity was calculated as .77 and specificity as .83. A strong positive correlation was found between test-retest MBI-C scores (r = .886, P < .0019). A strong positive correlation was found between MBI-C and NPI scores (r = .964, P < .001). MBI-C scores were significantly negatively correlated with MMSE and MoCA scores and positively correlated with GDS-15 scores. The results of our study showed that the Turkish version of the MBI-C is a valid and reliable measurement.

Behavioral Impairments and Increased Risk of Cortical Atrophy Risk Scores Among World Trade Center Responders.

Objective: World Trade Center (WTC) responders are susceptible to both cognitive and neuropsychiatric impairments, particularly chronic posttraumatic stress disorder. The present study examined self-reported behavioral impairments in a sample of 732 WTC responders, 199 of whom were determined to have high risk of WTC-related cortical atrophy by an artificial neural network. Results: We found that responders at increased risk of cortical atrophy showed behavioral impairment across five domains: motivation, mood, disinhibition, empathy, and psychosis (14.6% vs 3.9% in the low-risk group; P = 3.90 × 10-7). Factor analysis models revealed that responders at high risk of cortical atrophy tended to have deficits generalized across all aspects of behavioral impairment with focal dysfunction in sensory psychosis. We additionally describe how relationships are modulated by exposure severity and pharmacological treatments. Discussion: Our findings suggest a potential link between sensory deficits and the development of cortical atrophy in WTC responders and may indicate symptoms consistent with a clinical portrait of parietal dominant Alzheimer's disease or a related dementia (ADRD). Results underscore the importance of investigating neuropsychiatric symptomatology in clinical evaluations of possible ADRD.

An 11-Fold Higher Risk of Incident Mild Cognitive Impairment With Hispanic Ethnicity and Baseline Neuropsychiatric Symptoms.

OBJECTIVE: Neuropsychiatric symptoms (NPSs) have been linked to cognitive decline. This study explored ethnic differences and the effects of baseline NPSs on incident mild cognitive impairment (MCI) among 386 Hispanic and non-Hispanic participants from the Texas Harris Alzheimer's Research Study. METHODS: Data on NPSs from the Neuropsychiatric Inventory Questionnaire were available for all participants. Cox proportional hazards regression models were used to estimate the effect of ≥1 NPS at baseline and Hispanic ethnicity on incident MCI over a 7-year follow-up period. RESULTS: NPSs at baseline were associated with incident MCI for Hispanic participants but not non-Hispanic participants. Being Hispanic with at least one NPS at baseline had an 11-times higher risk of incident MCI. CONCLUSIONS: The Hispanic participants converted to MCI to a greater extent than the non-Hispanic participants. Only depressive symptoms increased the risk of MCI among non-Hispanics. Being of Hispanic ethnicity and having NPSs appeared to jointly increase the risk of progressing to MCI. To better understand the Alzheimer's disease continuum, further studies should explore other cultural, genetic, and medical risk factors influencing disease progression. Our findings strongly suggest the need to incorporate NPSs as outcomes of disease progression in future clinical trials involving Hispanic participants.