Loneliness is a highly prevalent experience in schizophrenia. Theoretical models developed in the general population propose that loneliness is tantamount to a feeling of being unsafe, is accompanied by enhanced environmental threat perception, and leads to poor physical, emotional, and cognitive functioning. Previous research has reported that loneliness is associated with poorer physical and emotional health in schizophrenia; however, few studies have directly compared loneliness and its correlates in persons with schizophrenia and non-psychiatric comparison subjects. The purpose of the current study was to evaluate similarities and differences in the construct of loneliness, the equivalency of the measurement of this construct, and similarities and differences in the pattern of external correlates of loneliness between schizophrenia and non-psychiatric comparison groups. The third version of the University of California, Los Angeles Loneliness Scale (UCLA-3) was administered to 116 individuals with schizophrenia or schizoaffective disorder and 106 non-psychiatric comparison subjects. Additional clinical and positive psychological measures were collected, as well as demographic characteristics of the two groups. Multiple groups confirmatory factor analysis revealed that the UCLA-3 was best characterized by a bifactor model in which all items loaded on a general loneliness dimension as well as one of two orthogonal method factors reflecting item wording in both groups. Furthermore, the UCLA-3 exhibited invariant measurement of these latent constructs across groups. Mean levels of loneliness were nearly a standard deviation higher in the schizophrenia group. Nonetheless, the overall pattern and strength of correlates were largely similar across groups, with loneliness being positively associated with depression, anxiety, and perceived stress, and negatively correlated with mental well-being, happiness, and resilience. Subtle differences in correlates of age, optimism, and satisfaction with life were found. Overall, loneliness appears to be distinct from other schizophrenia-related deficits and operates similarly across schizophrenia and NC groups, suggesting that theoretical models of loneliness developed in the general population may generalize to schizophrenia.

IMPORTANCE Wisdom is a neurobiological personality trait made up of specific components, including prosocial behaviors, emotional regulation, and spirituality. It is associated with greater well-being and happiness. OBJECTIVE To evaluate the effectiveness of interventions to enhance individual components of wisdom. DATA SOURCES MEDLINE and PsycINFO databases were searched for articles published through December 31, 2018.STUDY ELIGIBILITY CRITERIA Randomized clinical trials that sought to enhance a component of wisdom, used published measures to assess that component, were published in English, had a minimum sample size of 40 participants, and presented data that enabled computation of effect sizes were included in this meta-analysis.DATA EXTRACTION AND SYNTHESIS Random-effect models were used to calculate pooled standardized mean differences (SMDs) for each wisdom component and random-effects meta-regression to assess heterogeneity of studies.MAIN OUTCOMES AND MEASURES Improvement in wisdom component using published measures.RESULTS Fifty-seven studies (N = 7096 participants) met review criteria: 29 for prosocial behaviors, 13 for emotional regulation, and 15 for spirituality. Study samples included people with psychiatric or physical illnesses and from the community. Of the studies, 27 (47%) reported significant improvement with medium to large effect sizes. Meta-analysis revealed significant pooled SMDs for prosocial behaviors (23 studies; pooled SMD, 0.43 [95% CI, 0.22-0.3]; P = .02), emotional regulation (12 studies; pooled SMD, 0.67 [95% CI, 0.21-1.12]; P = .004), and spirituality (12 studies; pooled SMD, 1.00 [95% CI, 0.41-1.60]; P = .001). Heterogeneity of studies was considerable for all wisdom components. Publication bias was present for prosocial behavior and emotional regulation studies; after adjusting for it, the pooled SMD for prosocial behavior remained significant (SMD, 0.4 [95% CI, 0.16-0.78]; P = .003). Meta-regression analysis found that effect sizes did not vary by wisdom component, although for trials on prosocial behaviors, large effect sizes were associated with older mean participant age (β, 0.08 [SE, 0.04]), and the reverse was true for spirituality trials (β, −0.13 [SE, 0.04]). For spirituality interventions, higher-quality trials had larger effect sizes (β, 4.17 [SE, 1.07]), although the reverse was true for prosocial behavior trials (β, −0.91 [SE 0.44]).CONCLUSIONS AND RELEVANCE Interventions to enhance spirituality, emotional regulation, and prosocial behaviors are effective in a proportion of people with mental or physical illnesses and from the community. The modern behavioral epidemics of loneliness, suicide, and opioid abuse point to a growing need for wisdom-enhancing interventions to promote individual and societal well-being.

Introduction:The locus coeruleus (LC) undergoes extensive neurodegeneration in early Alzheimer's disease (AD). The LC is implicated in regulating the sleep-wake cycle, modulating cognitive function, and AD progression.This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Hypertension is common among older adults and is believed to increase susceptibility to Alzheimer’s disease, but mechanisms underlying this relationship are unclear. Hypertension also promotes circle of Willis atherosclerosis, which contributes to cerebral hypoperfusion and arterial wall stiffening, two potential mechanisms linking hypertension to Alzheimer’s disease. To examine the role of circle of Willis atherosclerosis in the association between hypertension and Alzheimer’s disease neuropathology, we analyzed post-mortem neuropathological data on 2198 decedents from the National Alzheimer’s Coordinating Center database (mean [standard deviation] age at last visit 80.51 [1.95] and 47.1% female) using joint simultaneous (i.e., mediation) modeling. Within the overall sample and among Alzheimer’s dementia decedents, hypertension was indirectly associated with increased neuritic plaques and neurofibrillary tangles through its association with circle of Willis atherosclerosis. Similar indirect effects were observed for continuous measures of systolic and diastolic blood pressure. These results suggest that hypertension may promote Alzheimer’s disease pathology indirectly through intracranial atherosclerosis by limiting cerebral blood flow and/or dampening perivascular clearance. Circle of Willis atherosclerosis may be an important point of convergence between vascular risk factors, cerebrovascular changes, and Alzheimer’s disease neuropathology.

Introduction: Apolipoprotein E (APOE) interacts with Alzheimer's disease pathology to promote disease progression. We investigated the moderating effect of APOE on independent associations of amyloid and tau positron emission tomography (PET) with cognition. Methods: For 297 nondemented older adults from the Alzheimer's Disease Neuroimaging Initiative, regression equations modeled associations between cognition and (1) cortical amyloid beta (Aβ) PET levels adjusting for tau and (2) medial temporal lobe (MTL) tau PET levels adjusting for Aβ, including interactions with APOE ε4-carrier status. Results: Adjusting for tau PET, Aβ was not associated with cognition and did not interact with APOE. In contrast, adjusting for Aβ PET, MTL tau was associated with all cognitive domains. Further, there was a stronger moderating effect of APOE on MTL tau and memory associations in ε4-carriers, even among Aβ-negative individuals. Discussion: Findings suggest that APOE may interact with tau independently of Aβ and that elevated MTL tau confers negative cognitive consequences in Aβ-negative ε4 carriers.

Introduction:Practice effects (PEs) on cognitive tests obscure decline, thereby delaying detection of mild cognitive impairment (MCI). Importantly, PEs may be present even when there are performance declines, if scores would have been even lower without prior test exposure. We assessed how accounting for PEs using a replacementparticipants method impacts incident MCI diagnosis.Methods: Of 889 baseline cognitively normal (CN) Alzheimer's Disease Neuroimaging Initiative (ADNI) participants, 722 returned 1 year later (mean age = 74.9 ± 6.8 at baseline). The scores of test-naïve demographically matched "replacement" participants who took tests for the first time were compared to returnee scores at follow-up.PEs-calculated as the difference between returnee follow-up scores and replacement participants scores-were subtracted from follow-up scores of returnees. PE-adjusted cognitive scores were then used to determine if individuals were below the impairmentThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Objective: Making decisions is central to the exercise of control over one’s well-being. Many individuals with serious mental illnesses (SMI) experience limitations in their decision making capacity. These individuals have often been placed under legal guardianship, and substitute decision makers have been appointed to make decisions on their behalf. More recently, Supported Decision Making (SDM) has emerged as a possible alternative in some cases. SDM involves recruitment of trusted supports to enhance an individual’s capacity in the decision making process, enabling them to retain autonomy in life decisions. This overview examines issues associated with decision making capacity in SMI, frameworks of substitute decision making and SDM, and emerging empirical research on SDM. Method: Overview of medical and legal literature. Results: Many, but not all, individuals with SMI exhibit decrements in decision making capacity and skill, in part due to cognitive impairment. There is no published data on rates of substitute decision making/guardianship or SDM for SMI. Only three empirical studies have explored SDM in this population. These studies suggest that SDM is viewed as an acceptable and potentially superior alternative to substitute decision making for patients and their caretakers. Conclusions: SDM is a promising alternative to substitute decision making for persons with SMI. Further empirical research is needed to clarify candidates for SDM, decisions in need of support, selection of supporters, guidelines for the SDM process, integration of SDM with emerging technological platforms, and outcomes of SDM. Recommendations for implementation of and research on SDM for SMI are provided.

Background Background: The Apathy Scale (AS), a popular measure of apathy in Parkinson's disease (PD), has been somewhat limited for failing to characterize dimensions of apathy, such as those involving cognitive, behavioral, and emotional apathy symptoms. This study sought to determine whether factors consistent with these apathy dimensions in PD could be identified on the AS, examine the associations between these factors and disease-related characteristics, and compare PD patients and healthy control (HCs) on identified factors. Methods Methods: Confirmatory (CFA) and exploratory factor analysis (EFA) were conducted on AS scores of 157 nondemented PD patients to identify AS factors. These factors were then correlated with important diseaserelated characteristics, and PD and HC participants were compared across these factors. ResultsResults: Previously proposed AS models failed to achieve an adequate fit in CFA. A subsequent EFA revealed two factors on the AS reflecting joint cognitive-behavioral aspects of apathy (Motivation-Interest-Energy) and emotional apathy symptoms (Indifference). Both factors were associated with anxiety, depression, healthrelated quality of life, and independent activities of daily living, with Indifference associated more with the latter. In addition, only the Indifference factor was associated with cognitive functioning. PD patients reported higher levels of symptoms than HCs on both factors, with the group difference slightly larger on the Motivation-Interest-Energy factor. Conclusion Conclusion: The AS can be decomposed into two factors reflecting Motivation-Interest-Energy and Indifference symptoms. These factors are differentially associated with clinical variables, including cognition and independent activities of daily living, indicating the importance of evaluating apathy from a multidimensional perspective.Apathy is among the most common psychiatric symptoms in Parkinson's disease (PD). Prevalence estimates of apathy in PD range from 17% to 62%. Although there is a substantial overlap between apathy and depression (e.g., common symptoms of lack of energy, fatigue, and loss of interest), a growing body of literature suggests that symptoms of apathy and depression are dissociable in PD, with 5% to 33% of individuals reporting apathy in isolation from any other psychiatric symptom. 1-8 This is likely attributed to nonoverlapping symptoms, such as diminished initiation and interests in the absence of affective evaluation in apathy as opposed to depression. 9 Apathy is associated with diminished quality of life, 10 a reduction in activities of daily living, 2,11 and may be a predictor of future executive dysfunction and global cognitive decline. 4,5,12 1 Veterans Administration San Diego Healthcare System,