Care of Older Adults with Mental Illness in Long-Term Care Residential Facility: A Scoping Review.

OBJECTIVES: Mental illness affects approximately 1 in 8 people globally, with approximately 15% of adults aged 60 years and older experiencing a mental disorder. With the aging population, there is a growing demand for long-term care. This scoping review focuses on older adults with non-neurocognitive and non-neurodevelopmental mental illnesses (NNNDMIs) in nursing homes, exploring how the care is provided. DESIGN: A scoping review. SETTING AND PARTICIPANTS: The review includes studies addressing care for older adults with NNNDMI in nursing homes. METHOD: The PRISMA-ScR protocol was followed. Four research databases (EBSCO, PubMed, Web of Science, and Scopus) and article bibliographies were used for the literature search. Thematic analysis identified the main themes. RESULTS: From a total of 1948 search results, 13 articles were analyzed to reveal 5 themes: (1) challenges and recommendations in nursing home admission for older adults with mental illness; (2) impact on the quality of the care; (3) need for specialized staff training and competency; (4) contributions to psychiatric and behavioral symptoms; and (5) need for a range of interventions. CONCLUSION AND IMPLICATIONS: Older adults with NNNDMI face barriers during admission to long-term care facilities that highlight concerns about care quality and systemic issues. Behavioral symptoms require specialized mental health support, but access to such services is lacking. Deficiencies in staff education and burnout prevention initiatives further underscore the need for comprehensive reforms to address the unique needs of this overlooked population in long-term care settings.

"Sustaining the burden". A qualitative study on the emotional impact and social functioning of family caregivers of patients with psychosis.

Evidence shows that caring for a family member with a psychotic disorder generates a significant emotional impact and repercussions on social functioning. However, this caregiving experience can be influenced by cultural factors. The aim of this study is to explore the experience and perception of a group of family caregivers of patients with psychotic disorders of different durations regarding the emotional and social functioning repercussions of caregiving on them in Andalusia. Three focus groups (28 participants) were conducted. Data were subject to a thematic analysis. Three themes emerged from the data: 1) Emotional invasion; 2) Disruption in the caregiver's life project; and 3) Changes in the family system. Participants reported experiencing sadness, fear, overwhelm, hopelessness, and uncertainty. Caregivers' accounts reflected an interruption of their daily tasks, as well as the need to reformulate plans or goals outside the family life that require long-term commitment, such as professional development or even their residence. The narratives indicated an impact on all roles within the family system, particularly for the mother. The results are consistent with existing research. Healthcare professionals and programs should take into account the costs associated with caregiving in order to minimize them, given the impact it has on both the patient's and the caregivers' health.

Effectiveness of Acceptance and Commitment Therapy on Psychotic Severity Among Inpatients With Primary Psychoses: A Randomized Controlled Trial.

This study investigated the effectiveness of acceptance and commitment therapy (ACT) compared to treatment as usual in managing psychotic symptoms, emotional dysregulation, recovery and psychological flexibility in inpatients with primary psychoses. The Primary outcome assessed the positive and negative syndrome scale, while the secondary outcomes were to assess difficulties in the emotion regulation scale, recovery assessment scale and acceptance and action questionnaire. An open-label, two-arm parallel randomized controlled trial was conducted. Participants diagnosed with primary psychoses were randomly assigned to either the ACT (n = 33) or treatment-as-usual (n = 32) group. The intervention included six structured sessions of ACT. ACT significantly reduced psychotic symptoms from 128 to 104 (Z = 5.01) compared to treatment as usual from 130 to 117 (Z = 4.88). Emotional regulation improved significantly in the ACT group from 73 to 55 (Z = 4.835) compared to treatment as usual from 73 to 70 (Z = 2.406). Recovery increased in the ACT group from 50 to 88 (Z = 5.01) compared to treatment as usual from 51 to 61 (Z = 4.93). Psychological flexibility improved in the ACT group from 33 to 25 (Z = 4.98) compared to treatment as usual from 33 to 31 (Z = 4.75). Between-group differences after intervention were significant for psychotic symptoms, emotional regulation, recovery and psychological flexibility (Z = 2.356, 4.652, 3.881 and 4.453, respectively). Accordingly, the current study demonstrates the effectiveness of ACT in reducing psychotic symptoms and improving emotional regulation, recovery and psychological flexibility in patients with primary psychoses. Integrating ACT into standard care protocols can enhance treatment outcomes, offering a comprehensive approach to managing complex mental health conditions. Trial Registration: ClinicalTrials.gov identifier: NCT06160869.

The New Horizon of Antipsychotics beyond the Classic Dopaminergic Hypothesis-The Case of the Xanomeline-Trospium Combination: A Systematic Review.

Although the dopamine hypothesis of schizophrenia explains the effects of all the available antipsychotics in clinical use, there is an increasing need for developing new drugs for the treatment of the positive, negative, and cognitive symptoms of chronic psychoses. Xanomeline-trospium (KarXT) is a drug combination that is based on the essential role played by acetylcholine in the regulation of cognitive processes and the interactions between this neurotransmitter and other signaling pathways in the central nervous system, with a potential role in the onset of schizophrenia, Alzheimer's disease, and substance use disorders. A systematic literature review that included four electronic databases (PubMed, Cochrane, Clarivate/Web of Science, and Google Scholar) and the US National Library of Medicine database for clinical trials detected twenty-one sources referring to fourteen studies focused on KarXT, out of which only four have available results. Based on the results of these trials, the short-term efficacy and tolerability of xanomeline-trospium are good, but more data are needed before this drug combination may be recommended for clinical use. However, on a theoretical level, the exploration of KarXT is useful for increasing the interest of researchers in finding new, non-dopaminergic, antipsychotics that could be used either as monotherapy or as add-on drugs.

Differential effects of cannabis constituents on schizophrenia-related psychosis: a rationale for incorporating cannabidiol into a schizophrenia therapeutic regimen.

Schizophrenia is a serious mental health disorder that confers one of the highest mortality rates of all psychiatric illnesses. Although the disorder's psychotic symptoms are treatable with conventional antipsychotics, they remain incurable. Moreover, medication adherence is poor, and individuals with schizophrenia choose to self-medicate with illicit substances, including cannabis. It is well-established that the delta-9-tetrahydrocannabinol (delta-9-THC) component of cannabis elicits psychotomimetic effects at high doses; worsens schizophrenia-related psychosis; commonly develops into cannabis use disorder in individuals with schizophrenia; and increases the risk of earlier-onset schizophrenia symptoms in those harboring genetic susceptibility. However, individuals with schizophrenia commonly use cannabis and cannabis derivatives such as cannabidiol (CBD). These products seem to alleviate psychotic symptoms and relieve adverse side effects of antipsychotic medications. Therefore, one notion that has gained traction is the potential utility of cannabis-derived cannabidiol (CBD) as adjunct treatment to reduce schizophrenia-associated psychosis and other symptoms. Currently, preclinical and clinical data remain inconclusive. The present review distinguishes the mechanisms underlying schizophrenia-associated vs. cannabis-induced psychosis; reviews the evidence for delta-9-THC-mediated exacerbation vs. CBD-mediated amelioration of schizophrenia-associated psychosis; and describes potential approaches for incorporating CBD into schizophrenia therapeutic regimen in a safe and efficacious manner.

The Characteristics of People with Serious Mental Illness Who are at High Risk for Hospitalization or Death.

Many individuals with serious mental illness are at high risk for hospitalization or death due to inadequate treatment of medical conditions or unhealthy behaviors. The authors describe demographic and clinical characteristics associated with increased risk in this population. Electronic data were obtained for individuals in treatment at a large Veterans' healthcare system who were at high risk according to a validated model. A random sample of these individuals was assessed in person. Multivariable regressions estimated the effect of numerous demographic, health, and clinical characteristics on risk. Emergency visits and hospitalizations were common. Greater risk was associated with being male, not married, and having more diagnoses. While risk varied by race, this effect was no longer significant after controlling for other factors. Health-related quality of life worsened with increasing risk. Routine data identify a large population of high-risk individuals who may benefit from outreach to provide healthcare services.

Effects of Recreational Cannabis Legalization on Mental Health: Scoping Review.

OBJECTIVE: Recreational cannabis legalization (RCL) is expanding rapidly. RCL's effects on mental health issues are of particular concern because cannabis use is more frequent among people receiving psychiatric care and is associated with several psychiatric disorders. The authors conducted a scoping review to examine the evidence and discern gaps in the literature concerning the effects of RCL on mental health and to assess the factors responsible for an observed heterogeneity in research results. METHODS: This scoping literature review followed PRISMA guidelines. Five databases-MEDLINE, CINAHL, Embase, APA PsycInfo, and Web of Science-were searched for English- or French-language reports published between January 1, 2012, and April 30, 2023. RESULTS: Twenty-eight studies from the United States and Canada were found. The studies were classified by category of the study's data (patients receiving psychiatric care [k=1], death records [k=4], emergency department or hospital records [k=10], and the general population [k=13]) and by the diagnosis (schizophrenia or psychoses, mood disorders, anxiety disorders and symptoms, suicide or suicidal ideation, or other mental health issues) examined. The review findings revealed a paucity of research and indicated mixed and largely inconclusive results of the studies examined. Research gaps were found in the examination of potential changes in cannabis use patterns among people receiving psychiatric care and in the availability of longitudinal studies. CONCLUSIONS: Clinicians, researchers, and policy makers need to collaborate to address the research gaps and to develop evidence-based policies that reflect a thorough understanding of the effects associated with RCL.

[Clinical and psychopathological characteristics of patients with late-onset schizophrenia and schizophrenia-like psychoses in clusters identified by biological parameters]. / Kliniko-psikhopatologicheskie kharakteristiki bol'nykh s pozdno manifestiruyushchimi shizofreniei i shizofrenopodobnymi psikhozami v klasterakh, vydelennykh po biologicheskim parametram.

OBJECTIVE: To assess clinical and psychopathological characteristics of late-aged female patients with late-onset psychoses in clusters formed on the basis of biochemical and immunological blood parameters. MATERIAL AND METHODS: We examined 59 women with schizophrenia and schizophrenia-like psychoses with onset after 40 years (ICD-10 F20, F22.8, F25, F23, F06.2), including 34 women with late-onset (40-60 years) and 25 with very late onset psychoses (after 60 years). At the time of hospitalization, a clinical/ psychopathological study was carried out using CGI-S, PANSS, CDSS, and HAMD-17, as well as the activities of glutathione reductase (GR) and glutathione-S-transferase (GT) have been determined in erythrocyte hemolysates, and the activities of leukocyte elastase (LE) and α1-proteinase inhibitor (α1-PI) have been assessed in blood plasma. Biochemical and immunological parameters have been also determined in 34 age-matched mentally healthy women. RESULTS: Clustering by signs such as GR, GT, LE and α1-PI has yielded two clusters of objects (patients) significantly different in GT (p<0.0001), LE (p<0.0001), and α1-PI (p<0.001) activities. Relatively to the controls, in the cluster 1 patients, the activities of GST and α1-PI are increased, the activity of LE is decreased, whereas, in the cluster 2 patients, the activity of GR is decreased, and the activities of LE and α1-PI are increased. Cluster 1 patients differ from cluster 2 patients in greater severity of the condition (CGI-S, p=0.04) and higher total scores on PANSS subscales' items. Cluster 1 includes 76% of patients with very late onset. Different correlations between clinical and biological signs are found in two clusters. CONCLUSION: The identified clusters have different clinical and psychopathological characteristics. Dividing patients into subgroups according to biochemical and immunological parameters is promising for the search for differentiated therapeutic approaches.

Steroid-induced mania in a patient with previously well-controlled organic bipolar 1-like affective disorder secondary to acquired brain injury: case report and literature review.

Steroid-induced neuropsychiatric sequelae are common, and pose significant risks to people usually receiving glucocorticoids in the context of physical illness. Steroid-induced mania and hypomania are the most common of the acute complications, yet despite great progress in understandings in neurophysiology there are no recent studies which review the factors which might predict who will experience this severe complication, nor are there consensus guidelines on management. We report the unusual case of a woman in her 50s admitted to a psychiatric unit with steroid-induced mania despite compliance with two mood stabilisers, several days after the administration of a Dexamethasone and Docetaxel chemotherapy regime adjunctive to lumpectomy for breast cancer. She had previously been diagnosed with an organic affective disorder (with classical bipolar 1 pattern) following severe ventriculitis related to ventricular drain insertion for obstructive hydrocephalus secondary to a colloid cyst. She had no psychiatric illness before this brain injury, but has a maternal history of idiopathic bipolar 1 affective disorder. Her episode of steroid-induced mania resolved following use of sedative medications, continuation of her existing mood stabilisers, and reductions of the steroid dosing in collaboration with her oncology team, which also protected her from further manic relapses during continued chemotherapy. Established mental illness, a family history, and acquired brain injury may reflect risk factors for steroid-induced mania through currently unclear pathways. Future epidemiological studies could better confirm these observations, and basic neuroscience may look to further explore the role of extrinsic glucocorticoids in the pathophysiology of affective disorders.

SARS-CoV-2 and Adolescent Psychiatric Emergencies at the Tübingen University Hospital: Analyzing Trends, Diagnoses, and Contributing Factors.

Psychiatric emergencies have increased in recent decades, particularly with the onset of the SARS-CoV-2 pandemic, and far too little is known about the backgrounds of these emergencies. In this study, we investigated the extent to which the number of psychiatric emergencies changed during and in the aftermath of the SARS-CoV-2 pandemic at the Child and Adolescent Psychiatry (CAP) Tübingen. We considered age and psychiatric diagnoses. Additionally, we evaluated the backgrounds of the emergencies. We applied a mixed- (quantitative and qualitative) methods approach to data on emergency presentations at the CAP Tübingen from the pre-SARS-CoV-2 pandemic period (October 2019-January 2020) to Restriction Phase 1 (October 2020-January 2021), Restriction Phase 2 (October 2021-January 2022), and endemic phase (October 2022-January 2023). The total number of emergencies and those with eating disorders and affective disorders increased, while obsessive-compulsive disorders, expansive disorders and anxiety disorders decreased. The patients presenting in the pre-SARS-CoV-2 pandemic period were younger than those in the subsequent periods. We content-coded the reasons behind the emergency presentations. We also identified four areas of stressors and personality characteristics associated with the emergency presentations. In light of the increasing number of psychiatric emergencies, the long-term aim should be to meet the growing demands and create options for prevention.

The Cascade of Care for Early Psychosis Detection in a College Counseling Center.

OBJECTIVE: Programs for early detection of psychosis help identify individuals experiencing emerging psychosis and link them with appropriate services, thereby reducing the duration of untreated psychosis (DUP). The authors used the cascade-of-care framework to identify various care stages between screening and enrollment in coordinated specialty care (CSC) and to determine attrition at each stage, with the goal of identifying points in the referral process that may affect DUP. METHODS: Project partners included a college counseling center and CSC program. All college students seeking mental health services at a counseling center between 2020 and 2022 (N=1,945) completed the Prodromal Questionnaire-Brief (PQ-B) at intake. Students who met the distress cutoff score were referred for a phone screening. Those who met criteria on the basis of this screening were referred for assessment and possible enrollment into CSC. RESULTS: Six stages in the cascade of care for early detection were identified. Of the students who completed the PQ-B as part of intake (stage 1), 547 (28%) met the PQ-B cutoff score (stage 2). Counselors referred 428 (78%) students who met the PQ-B cutoff score (stage 3), and 212 (50%) of these students completed the phone screening (stage 4). Seventy-two (34%) students completed a CSC eligibility assessment (stage 5), 21 (29%) of whom were enrolled in CSC (stage 6). CONCLUSIONS: The cascade-of-care framework helped conceptualize the flow within a program for early psychosis detection in order to identify stages that may contribute to lengthier DUP. Future research is warranted to better understand the factors that contribute to DUP at these stages.

Symptomatic and Functional Outcomes Among Individuals at High Risk for Psychosis Participating in Step-Based Care.

Validated, multicomponent treatments designed to address symptoms and functioning of individuals at clinical high risk for psychosis are currently lacking. The authors report findings of a study with such individuals participating in step-based care-a program designed to provide low-intensity, non-psychosis-specific interventions and advancement to higher-intensity, psychosis-specific interventions only if an individual is not meeting criteria for a clinical response. Among individuals with symptomatic or functional concerns at enrollment, 67% met criteria for a symptomatic response (median time to response=11.1 weeks), and 64% met criteria for a functional response (median time to response=8.9 weeks).

[History of the development of domestic psychiatry: the period 1940-1980]. / Istoriya razvitiya otechestvennoi psikhiatrii: period 1940­1980 gg.

The article briefly presents an analysis of the development of domestic psychiatry (with an emphasis on research in the field of psychopathology and nosology) from the post-war period (the Great Patriotic War) to the era of "perestroika". With the founding of the Institute of Psychiatry of the USSR Academy of Medical Sciences under the leadership of V.A. Gilyarovsky, the study of endogenous diseases was based on a multidisciplinary approach, in which the clinical-psychopathological research method was combined with clinical/biological ones. The most important role of the subsequent school of A.V. Snezhnevsky in describing the syndromes and forms of the course of schizophrenia (G.A. Rotshtein, R.A. Nadzharov, A.B. Smulevich, A.K. Anufriev), its age aspects (E.Ya. Sternberg; M.S. Vrono, G.P. Panteleeva, M.Ya. Tsutsulkovskaya; V.M. Bashina) is reflected. The contribution to psychopathology of other leading Russian psychiatrists, who worked mainly in Moscow and Leningrad research institutions of that period, was noted: students of P.B. Gannushkin - O.V. Kerbikov, V.M. Morozov, D.S. Ozeretskovsky, S.G. Zhislin, as well as G.K. Ushakov, A.E. Lichko, M.M. Kabanov, G.V. Morozov, M.V. Korkina, A.A. Portnov, I.N. Pyatnitskaya and others. The priority of A.V. Snezhnevsky and G.K. Avrutsky with colleagues for the introduction of neuroleptics and other new psychotropic drugs in the treatment of mental illnesses is emphasized. The review ends with the activities of M.E. Vartanyan who headed the country's leading scientific institution in the difficult «perestroika¼ era and developed the biological approach to mental illness further with the creation of international research programs.

Inflammation and cognitive performance in first-episode schizophrenia spectrum disorders: The moderating effects of childhood trauma.

In this study, we aimed to determine whether childhood trauma moderated the relationship between inflammation and cognitive functioning in persons with first-episode schizophrenia spectrum disorders (SSDs). We included data from 92 individuals who participated in the nationwide Early-Stage Schizophrenia Outcome study. These individuals completed the Childhood Trauma Questionnaire, provided a fasting blood sample for high-sensitivity C-reactive protein analysis, and underwent extensive neuropsychological testing. The intervening effects of age, sex, education, smoking status, and body mass index were controlled. Results indicated that childhood trauma levels significantly moderated the relationship between inflammation and four cognitive domains: speed of processing, working memory, visual memory, and verbal memory. Inflammation also predicted verbal memory scores irrespective of childhood trauma levels or the covariates. Upon further exploration, the significant moderation effects appeared to be primarily driven by males. In conclusion, a history of childhood trauma may be an important determinant in evaluating how inflammation relates to the cognitive performance of people with first-episode SSDs, particularly in speed of processing, working memory, visual memory, and verbal memory. We recommend that future researchers examining the effect of inflammation on cognitive functioning in SSDs include trauma as a moderating variable in their models and further examine additional moderating effects of sex.

The Interference of Negative Symptoms of Schizophrenia on Cognitive Domains: a Long-Term Observational Study on the Role of Clozapine.

The negative symptoms of schizophrenia are responsible for patients' worse quality of life. The association with cognitive deficits impairs clinical and psychopathological conditions. Our small 5-year observational study evaluated the efficacy of clozapine in negative and cognitive symptoms in schizophrenia inpatients. The overall results showed a significant improvement in the mean total scores of the BNSS and PANSS (at baseline (T0) vs five years (T3)). The improvement was also in some negative subscales (PANSS Negative Factor subscale) but not in others and the Epitrack tool. The overall results showed that clozapine is a useful therapeutic tool that does not affect the cognitive decline of these patients.

Negative Symptoms and Cognitive Deficits in Primary Psychoses: an Observational Study in a Psychiatric Rehabilitation Centre.

Negative symptoms (NSs) and cognitive deficits (CDs) negatively affect patients' quality of life with primary psychosis. Our observational study evaluated the percentage of NSs in a group of inpatients of a psychiatric rehabilitation facility and the variation of the interaction with CDs during the COVID-19 pandemic. The results showed a significant correlation between NSs and CDs in the first observation period (PANSS - FSNS p=0.001; BNSS p=0.023; Epitrack p=0.00) and a stabilization of the results between the first and second observation periods (PANSS - FSNS: p=0.094; BNSS p=0.466; Epitrack p=0.026).

Development and validation of a prediction model for rehospitalization among people with schizophrenia discharged from acute inpatient care.

Objective: Relapses and rehospitalization prevent the recovery of individuals with schizophrenia or related psychoses. We aimed to build a model to predict the risk of rehospitalization among people with schizophrenia or related psychoses, including those with multiple episodes. Methods: This retrospective cohort study included individuals aged 18 years or older, with schizophrenia or related psychoses, and discharged between January 2014 and December 2018 from one of three Japanese psychiatric hospital acute inpatient care ward. We collected nine predictors at the time of recruitment, followed up with the participants for 12 months, and observed whether psychotic relapse had occurred. Next, we applied the Cox regression model and used an elastic net to avoid overfitting. Then, we examined discrimination using bootstrapping, Steyerberg's method, and "leave-one-hospital-out" cross-validation. We also constructed a bias-corrected calibration plot. Results: Data from a total of 805 individuals were analyzed. The significant predictors were the number of previous hospitalizations (HR 1.42, 95% CI 1.22-1.64) and the current length of stay in days (HR 1.31, 95% CI 1.04-1.64). In model development for relapse, Harrell's c-index was 0.59 (95% CI 0.55-0.63). The internal and internal-external validation for rehospitalization showed Harrell's c-index to be 0.64 (95% CI 0.59-0.69) and 0.66 (95% CI 0.57-0.74), respectively. The calibration plot was found to be adequate. Conclusion: The model showed moderate discrimination of readmission after discharge. Carefully defining a research question by seeking needs among the population with chronic schizophrenia with multiple episodes may be key to building a useful model.

Autoimmune Encephalitis with Antibodies: Anti-NMDAR, Anti-AMPAR, Anti-GQ1b, Anti-DPPX, Anti-CASPR2, Anti-LGI1, Anti-RI, Anti-Yo, Anti-Hu, Anti-CV2 and Anti-GABAAR, in the Course of Psychoses, Neoplastic Diseases, and Paraneoplastic Syndromes.

Encephalitis is a condition with a variety of etiologies, clinical presentations, and degrees of severity. The causes of these disorders include both neuroinfections and autoimmune diseases in which host antibodies are pathologically directed against self-antigens. In autoimmune encephalitis, autoantibodies are expressed in the central nervous system. The incidence of this disease is approximately 4% of all reported cases of encephalitis. Autoimmune encephalitis can be induced by antibodies against neuronal surface antigens such as N-methyl-D-aspartate-activated glutamate receptors (NMDAR), α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors (AMPAR) or gangliosides GQ1b, DPPX, CASPR2, LGI1, as well as by antibodies against neuronal intracellular antigens. The paper presents a number of both mental and neurological symptoms of autoimmune encephalitis. Moreover, the coexistence of psychoses, neoplastic diseases, and the methods of diagnosing autoimmune encephalitis are discussed. Attention was also drawn to the fact that early diagnosis, as well as early initiation of targeted treatment, increases the chance of a successful course of the therapeutic process. Strategy and Methodology: The articles on which the following paper was based were searched using search engines such as PubMed and Medline. Considering that anti-NMDAR antibodies were first described in 2007, the articles were from 2007 to 2023. The selection of papers was made by entering the phrases "autoimmune encephalitis and psychosis/paraneplastic syndromes or cancer". The total number of articles that could be searched was 747, of which 100 items were selected, the most recent reports illustrating the presented topic. Thirty-four of them were rejected in connection with case reports or papers that could not be accessed.

Clinical response to treatment with a partial dopamine agonist is related to changes in reward processing.

Aberrant neuronal coding of reward processing has been linked to psychosis. It remains unresolved how treatment with a partial dopamine agonist affects reward processing, and whether treatment affects reward processing differently in patients responding and not responding to treatment. Here, 33 antipsychotic-naïve psychosis patients and 33 matched healthy controls underwent functional magnetic resonance imaging before and after patients received aripiprazole monotherapy for six weeks. Processing of motivational salient events and negative outcome evaluation (NOE) was examined using a monetary incentive delay task. Psychopathology was assessed with the Positive and Negative Syndrome Scale, and responders were identified by having ≥30% reduction in positive symptoms (N=21). At baseline, patients displayed an increased NOE signal in the caudate and dorsolateral prefrontal cortex compared to healthy controls. In the caudate, the NOE signal was normalized at follow-up, and normalization was driven by responders. In responders only, there was a significant improvement in the motivational salience signal in the caudate at follow-up. Motivational salience and NOE signals in the caudate may be associated with a dopaminergic mechanism in patients characterized as responders which may not be the case in non-responders. Likewise, non-dopaminergic mechanism may underly abnormal NOE processing in dorsolateral prefrontal cortex.

Neurodegenerative pathologies associated with behavioral and psychological symptoms of dementia in a community-based autopsy cohort.

In addition to the memory disorders and global cognitive impairment that accompany neurodegenerative diseases, behavioral and psychological symptoms of dementia (BPSD) commonly impair quality of life and complicate clinical management. To investigate clinical-pathological correlations of BPSD, we analyzed data from autopsied participants from the community-based University of Kentucky Alzheimer's Disease Research Center longitudinal cohort (n = 368 research volunteers met inclusion criteria, average age at death 85.4 years). Data assessing BPSD were obtained approximately annually, including parameters for agitation, anxiety, apathy, appetite problems, delusions, depression, disinhibition, hallucinations, motor disturbance, and irritability. Each BPSD was scored on a severity scale (0-3) via the Neuropsychiatric Inventory Questionnaire (NPI-Q). Further, Clinical Dementia Rating (CDR)-Global and -Language evaluations (also scored on 0-3 scales) were used to indicate the degree of global cognitive and language impairment. The NPI-Q and CDR ratings were correlated with neuropathology findings at autopsy: Alzheimer's disease neuropathological changes (ADNC), neocortical and amygdala-only Lewy bodies (LBs), limbic predominant age-related TDP-43 encephalopathy neuropathologic changes (LATE-NC), primary age-related tauopathy (PART), hippocampal sclerosis, and cerebrovascular pathologies. Combinations of pathologies included the quadruple misfolding proteinopathy (QMP) phenotype with co-occurring ADNC, neocortical LBs, and LATE-NC. Statistical models were used to estimate the associations between BPSD subtypes and pathologic patterns. Individuals with severe ADNC (particularly those with Braak NFT stage VI) had more BPSD, and the QMP phenotype was associated with the highest mean number of BPSD symptoms: > 8 different BPSD subtypes per individual. Disinhibition and language problems were common in persons with severe ADNC but were not specific to any pathology. "Pure" LATE-NC was associated with global cognitive impairment, apathy, and motor disturbance, but again, these were not specific associations. In summary, Braak NFT stage VI ADNC was strongly associated with BPSD, but no tested BPSD subtype was a robust indicator of any particular "pure" or mixed pathological combination.