A voxel- and source-based morphometry analysis of grey matter volume differences in very-late-onset schizophrenia-like psychosis.

BACKGROUND: Very-late-onset schizophrenia-like psychosis (VLOSLP) is associated with significant burden. Its clinical importance is increasing as the global population of older adults rises, yet owing to limited research in this population, the neurobiological underpinnings of VLOSP remain insufficiently clarified. Here we address this knowledge gap using novel morphometry techniques to investigate grey matter volume (GMV) differences between VLOSLP and healthy older adults, and their correlations with neuropsychological scores. METHODS: In this cross-sectional study, we investigated whole-brain GMV differences between 35 individuals with VLOSLP (mean age 76.7, 26 female) and 36 healthy controls (mean age 75.7, 27 female) using whole-brain voxel-based morphometry (VBM) and supplementary source-based morphometry (SBM) on high resolution 3D T1-weighted MRI images. Additionally, we investigated relationships between GMV differences and cognitive function assessed with an extensive neuropsychological battery. RESULTS: VBM showed lower GMV in the thalamus, left inferior frontal gyrus and left insula in patients with VLOSLP compared to healthy controls. SBM revealed lower thalamo-temporal GMV in patients with VLOSLP. Processing speed, selective attention, mental flexibility, working memory, verbal memory, semantic fluency and confrontation naming were impaired in patients with VLOSLP. Correlations between thalamic volumes and memory function were significant within the group of individuals with VLOSLP, whereas no significant associations remained in the healthy controls. CONCLUSIONS: Lower GMV in the thalamus and fronto-temporal regions may be part of the underlying neurobiology of VLOSLP, with lower thalamic GMV contributing to memory impairment in the disorder.

Ghosts from the past? The association between childhood interpersonal trauma, attachment and anxiety and depression in late life.

Objectives: Research suggests that vulnerability for anxiety and depression in late life results from a complex interaction between (neuro)biological and environmental factors. In this context, there is growing evidence for the role of childhood trauma on vulnerability for both anxiety and depression throughout the course of life, mainly through its effects on attachment as a biologically based neurodevelopmental stress regulation system. Yet, the impact of childhood trauma on depression and anxiety in late life specifically remains unclear. The current study therefore aims to investigate the association between retrospectively reported childhood interpersonal trauma, attachment dimensions and levels of anxiety and depression in late life.Method: A sample of 81 community dwelling older adults completed measures of early and current adversity, attachment dimensions, and levels of anxiety and depression.Results: The occurrence and frequency of childhood trauma, but not later negative adult life events, was associated with late life anxiety and depression. Both attachment anxiety and avoidance were related to anxiety and depression. Only attachment anxiety affected the association between childhood trauma, and emotional neglect in particular, and late life anxiety and depression.Conclusion: Childhood trauma may be associated with anxiety and depression in late life. Part of this association is probably indirect, via the effect of insecure attachment and high levels of attachment anxiety in particular.

Dissecting Digital Card Games to Yield Digital Biomarkers for the Assessment of Mild Cognitive Impairment: Methodological Approach and Exploratory Study.

BACKGROUND: Mild cognitive impairment (MCI), the intermediate cognitive status between normal cognitive decline and pathological decline, is an important clinical construct for signaling possible prodromes of dementia. However, this condition is underdiagnosed. To assist monitoring and screening, digital biomarkers derived from commercial off-the-shelf video games may be of interest. These games maintain player engagement over a longer period of time and support longitudinal measurements of cognitive performance. OBJECTIVE: This paper aims to explore how the player actions of Klondike Solitaire relate to cognitive functions and to what extent the digital biomarkers derived from these player actions are indicative of MCI. METHODS: First, 11 experts in the domain of cognitive impairments were asked to correlate 21 player actions to 11 cognitive functions. Expert agreement was verified through intraclass correlation, based on a 2-way, fully crossed design with type consistency. On the basis of these player actions, 23 potential digital biomarkers of performance for Klondike Solitaire were defined. Next, 23 healthy participants and 23 participants living with MCI were asked to play 3 rounds of Klondike Solitaire, which took 17 minutes on average to complete. A generalized linear mixed model analysis was conducted to explore the differences in digital biomarkers between the healthy participants and those living with MCI, while controlling for age, tablet experience, and Klondike Solitaire experience. RESULTS: All intraclass correlations for player actions and cognitive functions scored higher than 0.75, indicating good to excellent reliability. Furthermore, all player actions had, according to the experts, at least one cognitive function that was on average moderately to strongly correlated to a cognitive function. Of the 23 potential digital biomarkers, 12 (52%) were revealed by the generalized linear mixed model analysis to have sizeable effects and significance levels. The analysis indicates sensitivity of the derived digital biomarkers to MCI. CONCLUSIONS: Commercial off-the-shelf games such as digital card games show potential as a complementary tool for screening and monitoring cognition. TRIAL REGISTRATION: ClinicalTrials.gov NCT02971124; https://clinicaltrials.gov/ct2/show/NCT02971124.

The Neuropsychological Profile and Phenomenology of Late Onset Psychosis: A Cross-sectional Study on the Differential Diagnosis of Very-Late-Onset Schizophrenia-Like Psychosis, Dementia with Lewy Bodies and Alzheimer's Type Dementia with Psychosis.

OBJECTIVE: Late onset psychosis not only occurs as a prodromal symptom to neurodegeneration, but it can also be associated with a non-progressive mild cognitive deficit. Studying the phenomenology of psychotic symptoms and the neuropsychological profile may serve as sensitive and non-invasive tools for differential diagnosis. METHOD: We compared 57 individuals with very-late-onset schizophrenia-like psychosis (VLOSLP), 49 participants with Dementia with Lewy Bodies (DLB) and 35 patients with Alzheimer's type Dementia and psychosis (AD+P) concerning the phenomenology of psychotic symptoms and the neuropsychological profile using several measures of cognitive function in a cross-sectional study. RESULTS: Participants with DLB exhibited more visual hallucinations, especially those involving animals, and less partition/paranoid delusions than both other groups. VLOSLP showed more partition delusions and auditory hallucinations of human voices than both other groups. Hence, patients with DLB and VLOSLP showed greater dissimilarity in the phenomenology of psychosis, whereas individuals with AD+P held an intermediate position. Processing speed and executive function were comparably impaired among the three groups, as was expected considering a common underlying set of neurobiological abnormalities for psychosis. However, AD+P showed more strongly reduced learning and consolidation skills, whereas DLB was associated with prominent visuoconstructive deficits. CONCLUSIONS: Phenomenology of psychosis may prove especially informative when comparing individuals with DLB to those with VLOSLP. Neuropsychological profiles are able to further aid differential diagnosis of the three groups.

Reduced tendency to attribute mental states to abstract shapes in behavioral variant frontotemporal dementia links with cerebellar structural integrity.

Theory of mind (ToM) refers to the ability to attribute mental states to others. Behavioral variant frontotemporal dementia (bvFTD) is a neurodegenerative disorder characterized by profound deficits in social cognition, including ToM. We investigate whether bvFTD affects intention attribution tendency while viewing abstract animations and whether this might represent a primary deficit. A sample of 15 bvFTD patients and 19 matched controls were assessed on cognition and performed an implicit ToM task. They were instructed to describe what they observed in movement patterns displayed by geometrical shapes (triangles). These movement patterns either represented animacy, goal-directed actions or manipulation of mental state (ToM). The responses were scored for both accuracy and intentionality attribution. Using Voxel-Based Morphometry, we investigated the structural neuroanatomy associated with intention attribution tendency. The behavioral results revealed deficits in the bvFTD group on intentionality attribution that were specific for the ToM condition after controlling for global cognitive functioning (MMSE-score), visual attention (TMT B-score), fluid intelligence (RCPMT-score) and confrontation naming (BNT-score). In the bvFTD sample, the intention attribution tendency on the ToM-condition was associated with grey matter volume of a cluster in the cerebellum, spanning the right Crus I, Crus II, VIIIb, IX, left VIIb, IX and vermal IX and X. The results reveal a specific, primary, implicit domain-general ToM deficit in bvFTD that cannot be explained by cognitive dysfunction. Furthermore, the findings point to a contribution of the cerebellum in the social-cognitive phenotype of bvFTD.

The neuropsychology and neurobiology of late-onset schizophrenia and very-late-onset schizophrenia-like psychosis: A critical review.

OBJECTIVE: The current review discusses neuropsychological profiles and the longitudinal course of cognitive dysfunction in Late Onset Schizophrenia (LOS) and Very-late-onset schizophrenia-like psychosis (VLOSLP), and attempts to clarify its neurobiological underpinnings. METHOD: A systematic literature search resulted in 29 publications describing original research on the neuropsychology of LOS/VLOSLP and 46 studies focussing on neurobiology. RESULTS: Although mildly progressive cognitive impairment is usually present, only a subgroup of LOS/VLOSLP develops dementia during a 10-year follow-up succeeding the onset of psychosis. This coincides with the absence of neuropathological evidence for neurodegeneration in many cases. Cognitive deterioration is characterized by deficits in (working) memory, language, psychomotor speed and executive functioning. Underlying neurobiological changes encompass white matter pathology, increased ventricle-to-brain ratio (VBR) with coinciding atrophy and hypo-metabolism of frontal, temporal and subcortical areas. CONCLUSIONS: Multiple changes in neurobiology and cognition contributing to LOS/VLOSLP may reflect stress-related accelerated brain aging rather than neurodegenerative pathology. Their involvement in the onset of illness, however, might be inversely proportional to pre-existing (psychosocial and/or genetic) vulnerability to psychosis.

Attachment in old age: theoretical assumptions, empirical findings and implications for clinical practice.

Contemporary theoretical models that conceptualize attachment as a biologically-based behavioral system that is activated under threat offer a heuristic theoretical framework to understand processes involved in aging and particularly individual differences in coping with the inevitable losses associated with aging and age-related disease, including dementia. This paper provides a systematic qualitative review of research concerning attachment in old age published between 1983 and June 2012. Four major findings emerged. First, studies suggest age-related changes with regard to the number and type of attachment figures, with older adults, compared to younger adults, having less attachment relations. Moreover, so-called symbolic attachments (e.g., to God or a deceased loved one) become more prominent in old age. Second, the quality of attachment changes with increasing age, with significant decreases in attachment anxiety, but not in attachment avoidance. Third, late-life attachment is in theoretically predicted ways associated with indices of intraindividual and interindividual functioning. Finally, insecure attachment has a negative impact on subjective caregiver burden and behavior of patients with dementia. There is some evidence suggesting that attachment-based interventions show positive effects in treating problem behaviors associated with dementia. However, these conclusions need to be interpreted within the context of important methodological limitations, stressing the need for future research in this domain. Guidelines for future research are outlined.