Very Late-onset Schizophrenia-like Psychosis Research Articles

Impact of loneliness and social isolation in older people in Japan

A decline in social functioning is a hallmark of dementia and is associated with worsening cognitive impairment, various behavioral and psychological symptoms, and caregiver burden. Since the feeling of loneliness is related to social function decline in people with mild cognitive impairment (MCI) and dementia, care for the social isolation that can cause loneliness is considered important in Japan, where the number of older people living alone is increasing.In addition to dementia, late-onset psychosis is also known to be affected by loneliness and social isolation. Psychosis that develops after age 60 and does not involve organic or affective disorders is defined as very late-onset schizophrenia-like psychosis (VLOSLP) and is known to be different in quality from psychosis that develops at a younger age. Social isolation has been reported as one of risk factors of VLOSLP, and although people with VLOSLP are independent in daily life, their social functioning is impaired in a way that is different from dementia due to their abnormalities in the content of thinking. Therefore, social isolation and decline of social functioning are also major problems for VLOSLP. Longitudinally, people with VLOSLP are more likely than the general older population to progress to dementia including Lewy body disease and Alzheimer’s disease subtypes. With the increasing importance of early diagnosis and intervention of these neurodegenerative diseases, identification and intervention of people with VLOSLP is a challenging but important topic.We are now investigating the use of robots with communication capabilities aiming to improve loneliness and social isolation of older people living alone with MCI, mild dementia and VLOSLP. On the other hand, we have found that loneliness in MCI and mild dementia does not necessarily correlate with social isolation status, such as living alone, indicating that loneliness and social isolation among older people requires further research.

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

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. 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. 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. 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.

Vascular Schizophrenia-like Psychosis in Older Adults.

The aims of this study were to analyze prevalence and severity of vascular risk factors in older patients referred to our clinic due to onset of Very Late-Onset Schizophrenia-Like Psychosis (VLOSLP) and to create a specific phenotype based on pathophysiological insight rather than age of onset. In a longitudinal study, 103 (M = 39, F = 64; mean age of 80.32 ± 7.65 years) patients were evaluated with cognitive, neuropsychiatric, and functional assessment scales. Blood concentration of hemoglobin (Hb), mean corpuscular volume (MCV), platelets, total protein test (TPT), creatinine, azotemia, glycemia, total cholesterol (TC), triglycerides (TG), uric acid (UA), sodium (Na), potassium (K), chlorine (Cl), calcium (Ca), folate, vitamin B12 (Vit-B12), and homocysteine were measured. Presence/absence of tobacco use, alcohol consumption, psychoactive substance use, hypertension, hyperlipidemia, diabetes mellitus, and history of vascular disease were collected. Females were more apathetic than males (NPI-Apathy: p = 0.040). Males had a significantly higher level of Hb (p = 0.019) and UA (p = 0.001), and a lower level of platelets (p = 0.004) and Ca (p = 0.003), and used more tobacco (p = 0.046) and alcohol (p = 0.024) than females. Comparing patients < 80 and ≥80 years, we found differences in frequency of vascular risk factors among men (p = 0.027). In total, 102 patients were treated for psychosis (59.16% of them were using atypical antipsychotics). The results of this study could be useful for a progressive demonstration of the causal relationship between cardiac and cerebral vascular events and VLOSLP.

VERY LATE-ONSET SCHIZOPHRENIA-LIKE PSYCHOSIS: CASE REPORT AND CRITICAL LITERATURE REVIEW.

Late-life psychosis presents a challenge, wherein a wide range of differential diagnoses should be considered. Very late-onset schizophrenia-like psychosis (VLOSLP) is a nosological entity that remains a conundrum. We provide a comprehensive literature review on the neurobiological underpinnings of VLOSLP. We describe a case that typifies the clinical presentation of VLOSLP. Although not pathognomonic, certain features, namely the two-stage progression of psychotic episode, partition delusions, multimodal hallucinations, and absent formal thought disorder or negative symptoms, are quite suggestive of VLOSLP. Several medical causes that might cause late-life psychosis, including neuroinflammatory/immunology diseases, were ruled out. Neuroimaging revealed basal ganglia lacunar infarctions along with chronic white matter small-vessel ischemic disease. The diagnosis of VLOSLP is based on clinical evidence, and the aforementioned clinical features support this diagnostic hypothesis. This case adds to the growing body of evidence pertaining to the relevance of cerebrovascular risk factors in the pathophysiology of VLOSLP, alongside age-specific neurobiological processes. We hypothesized that microvascular brain lesions disrupt the frontal-subcortical circuitry and uncover other core neuropathological processes. Future research should focus on identifying a specific biomarker that would allow clinicians to more accurately diagnose VLOSLP, differentiate it from other overlapping clinical entities such as dementia or post-stroke psychosis, and provide a tailored treatment for the patient.

Usefulness of Low-Dose Olanzapine for Initial and Maintenance Treatments of Very-Late-Onset Schizophrenia-Like Psychosis: A Case Report

In pharmacotherapy for schizophrenia, it is recommended that antipsychotic medications should not be discontinued, and their dosage should not be reduced during the stabilization and maintenance phases. Nevertheless, these drugs also have side effects that can increase extrapyramidal symptoms and mortality in the elderly population. It is yet to be determined whether antipsychotics should be reduced or discontinued in patients with very-late-onset schizophrenia-like psychosis (VLOSLP) during the stabilization and maintenance stages. Therefore, we describe the case of an elderly woman for whom low-dose olanzapine was useful throughout the initial, stabilization, and maintenance phases of VLOSLP. The patient was a 70-year-old woman who had experienced persistent hallucinations and delusions for 3 years. Two years after her diagnosis, except for relapse due to self-discontinuation, she remained in remission of her psychotic symptoms by continuing olanzapine treatment (2.5 mg/day). The standard effective dose of olanzapine was 10 mg/day, and she was able to respond to therapy with a low dose of olanzapine in the initial and subsequent phases of stabilization and maintenance. It is suggested that the discontinuation of antipsychotics should be avoided to avoid recurrence, even if the dose is lower than the standard amount during the stabilization and maintenance phases. Additionally, if the patient progresses to dementia, the treatment approach may vary, and it is imperative to monitor cognitive decline and self-discontinuation of oral medications during the follow-up of VLOSLP.

Characteristics of very late-onset schizophrenia-like psychosis classified with the biomarkers for Alzheimer's disease: a retrospective cross-sectional study.

We aimed to investigate the association between very late-onset schizophrenia-like psychosis (VLOSLP), a schizophrenia spectrum disorder with an onset of ≥60 years, and Alzheimer's disease (AD) using biomarkers. Retrospective cross-sectional study. Neuropsychology clinic of Osaka University Hospital in Japan. Thirty-three participants were classified into three groups: eight AD biomarker-negative VLOSLP (VLOSLP-AD), nine AD biomarker-positive VLOSLP (VLOSLP+AD), and sixteen amnestic mild cognitive impairment due to AD without psychosis (aMCI-P+AD) participants. Phosphorylated tau levels in the cerebrospinal fluid and 18F-Florbetapir positron emission tomography results were used as AD biomarkers. Several scales (e.g. the Mini-Mental State Examination (MMSE), Wechsler Memory Scale-Revised (WMS-R) Logical Memory (LM) I and II, and Neuropsychiatric Inventory (NPI)-plus) were conducted to assess clinical characteristics. Those in both VLOSLP-AD and +AD groups scored higher than those in aMCI-P+AD in WMS-R LM I. On the other hand, VLOSLP+AD participants scored in between the other two groups in the WMS-R LM II, with only VLOSLP-AD participants scoring significantly higher than aMCI-P+AD participants. There were no significant differences in sex distribution and MMSE scores among the three groups or in the subtype of psychotic symptoms between VLOSLP-AD and +AD participants. Four VLOSLP-AD and five VLOSLP+AD participants harbored partition delusions. Delusion of theft was shown in two VLOSLP-AD patients and five VLOSLP+AD patients. Some VLOSLP patients had AD pathology. Clinical characteristics were different between AD biomarker-positive and AD biomarker-negative VLOSLP, which may be helpful for detecting AD pathology in VLOSLP patients.

Pineal volume reduction as the neural correlate of very late-onset schizophrenia-like psychosis.

This study aimed to examine the relationship between pineal parenchymal volume (PPV) and schizophrenia-like psychosis (SLP) at the onset of ≥60 years. Exactly 21 patients with SLP, 50 with Alzheimer's disease (AD) with delusions of theft, and 35 with normal cognition were selected. The PPVs in patients with SLP and patients with AD with delusional theft were significantly lower than those in patients with normal cognition. Moreover, PPVs in nine patients with Very late-onset schizophrenia-like psychosis (VLOSLP) tended to be lower than that in patients with normal cognition. Thus, pineal volume reduction could be a neural correlate of VLOSLP.

Characteristics of very late-onset schizophrenia-like psychosis as prodromal dementia with Lewy bodies: a cross-sectional study

BackgroundThis study aimed to identify cases of potential prodromal DLB in very late-onset schizophrenia-like psychosis (VLOSLP), using indicative biomarkers of dementia with Lewy bodies (DLB), and to evaluate the characteristics of psychosis as prodromal DLB.MethodsData of patients with VLOSLP without dementia and Parkinsonism, who underwent testing for at least one indicative biomarker of DLB, were retrospectively collected from the database of the psychiatry clinic at the Osaka University Hospital. Patients were divided into two groups based on the positive (VLOSLP+LB) and negative (VLOSLP–LB) results of the indicative biomarkers of DLB. Age, gender, cognitive battery scores, prevalence of each type of delusions and hallucinations, cerebral volume, and cerebral perfusion were compared between the two groups.ResultsEleven VLOSLP+LB and 23 VLOSLP–LB participants were enrolled. There were no significant differences in age, proportion of females, and MMSE scores between the two groups. The standardized score of the digit symbol substitution test was significantly lower in the VLOSLP+LB than in VLOSLP–LB group (6.9 [3.1] vs. 10.0 [2.7], p = 0.005). The prevalence of visual hallucinations was significantly higher in the VLOSLP+LB group than in the VLOSLP-LB group (81.8% vs. 26.1%, p = 0.003). Auditory hallucinations were prevalent in both groups (43.5% in VLOSLP–LB, and 45.5% in VLOSLP+LB). Among patients with auditory hallucinations, auditory hallucinations without coexistent visual hallucinations tended to be more prevalent in VLOSLP–LB (7 out of 10) than in VLOSLP+LB patients (1 out of 5). Although cerebral volume was not different in any region, cerebral perfusion in the posterior region, including the occipital lobe, was significantly lower in the VLOSLP+LB group.ConclusionsPsychomotor slowing, visual hallucinations, and reduced perfusion in the occipital lobe may be suggestive of prodromal DLB in VLOSLP patients, even though the clinical manifestations were similar in many respects between VLOSLP+LB and VLOSLP–LB. Although auditory hallucinations were prevalent in both groups, most patients in VLOSLP+LB complained of auditory hallucinations along with visual hallucinations. Future studies with a larger number of patients without selection bias are desirable.

Late Onset Psychosis and Grave's Disease: A Case Report

<h3>Introduction</h3> Prevalence of late life psychosis is 23%, however 60% of new onset psychosis in older individuals are of secondary etiology (Cohen, 2015). Psychosis in the elderly individuals could be primarily due to Very Late Onset Schizophrenia Like Psychosis (VLOSLP) vs secondary causes (Delirium, Dementia, Drugs/illicit substances/toxin, Medical conditions including autoimmune conditions.) The apparent link between autoimmune disorders and psychotic disorders has received increased interest in the last decades (Benros, 2019). A significant positive association was observed for pernicious anemia (OR = 1.91; 95% CI, 1.29–2.84), pemphigoid (OR = 1.90; 95% CI, 1.62– 2.24), psoriasis (OR = 1.70; 95% CI, 1.51–1.91), celiac disease (OR = 1.53; 95% CI, 1.12–2.10), and Graves' disease (OR = 1.33; 95% CI, 1.03–1.72) (Cullen, 2019). In this poster, we are presenting a case of a patient with Grave's disease presenting with first episode of psychosis at late age. <h3>Methods</h3> Elmhurst Hospital Center (EHC) is uniquely placed 545 bedded Hospital having 6 psychiatric inpatient units. We are presenting a case of a patient who was admitted in one of the psychiatric inpatient units. We reviewed studies and reviews over the past 10 years using PubMed, Medline and Google Scholar. Search terms included "psychosis", "autoimmune psychosis", "grave's disease" "autoimmune disorders" "very late onset psychosis" "geriatric psychosis". We reviewed available literature with regards to first episode of psychosis in old age and psychosis in autoimmune disorders specially Grave's disease. <h3>Results</h3> Stratified analyses revealed that not only is there increased comorbidity between NNAI (Non-Neurological Autoimmune) disorders and psychosis, but also NNAI disorders increase the risk for subsequent psychosis and vice versa (Alexis E. Cullen, 2019). Graves' disease which is the most common cause of hyperthyroidism, is also known to be linked to neuropsychiatric issues, and some even present with psychotic disorders (Benros, 2019). A German study found that in a cohort of 100 patients with a schizophreniform illness, 19 had increased antithyroid autoantibodies in sera, and 13 showed signs of intrathecal synthesis hereof (Endres D, 2017). Multiple factors have been suggested to underlie the observed association between NNAI disorders and psychosis, including inflammation, shared genetic vulnerability, predisposing infections, and brain-reactive antibodies (Benros ME, 2014). Along with the abovementioned possible mechanisms, in Grave's disease or hyperthyroidism, adrenergic hyperactivity is hypothesized to be a major cause of psychiatric symptoms (Bunevic?ius, 2010). Our patient's psychotic presentation substantially subsided as pharmacological interventions were taken for both hyperthyroidism and psychotic symptoms. While there have been gradually increasing literature on the association between autoimmune disorder such as Grave's disease and psychosis, there is limited work on the treatment recommendations and prognosis. <h3>Conclusions</h3> Our case is an example of psychosis of secondary etiology (due to autoimmune condition). Research on the field of psychoimmunology is gradually evolving. Most of the available literature is on the possible mechanisms of the association between autoimmune disorders including Grave's disease and psychosis. When patients present with first episode of psychosis at late age, a thorough evaluation and examination are required to rule out possible underlying medical etiologies. Similarly, when patients are diagnosed with Grave's disease and other autoimmune disorders, careful longitudinal monitoring is warranted for the early signs of psychosis. Further expansion of studies is required for targeted treatment recommendations and overall prognosis in such cases. <h3>This research was funded by</h3> No conflict of interest. <h3>References</h3> Jeppesen R and Benros ME (2019) Autoimmune Diseases and Psychotic Disorders. Front. Psychiatry 10:131. doi: 10.3389/fpsyt.2019.00131 Endres D, Dersch R, Hochstuhl B, Fiebich B, Hottenrott T, Perlov E, et al. Intrathecal thyroid autoantibody synthesis in a subgroup of patients with schizophreniform syndromes. J Neuropsychiatry Clin Neurosci. (2017) 29:365–74. doi: 10.1176/appi.neuropsych.16110296 Benros ME, Eaton WW, Mortensen PB (2014): The epidemiologic evidence linking autoimmune diseases and psychosis. Biol Psychiatry 75:300–306. Alexis E. Cullen, S. H. (2019). Associations Between Non-neurological Autoimmune Disorders and Psychosis: A Meta-analysis. Biological Psychiatry, 85:35–48.

P/Q-Type Calcium Channel Antibodies and Late Life First Break Psychosis: A Case Report

<h3>Introduction</h3> Paraneoplastic Syndrome, described in the 1940s, a phenomenon of cancer presenting with multiple different manifestations, not directly related to tumor itself, has had an overdue recognition with these conditions still being studied and researched, especially when it comes to Paraneoplastic Syndromes presenting with Neuropsychiatric Disorders (Lorraine C. Pelosof, 2010). In the psychiatric and neurological literature, there is slow yet gradual recognition of new onset psychosis in patients with no prior history of such, which are attributable to autoantibodies of different types. In some psychiatric literature, this presentation is termed as autoimmune psychosis (Thomas A Pollak, 2020). Currently known autoantigens include NMDAR, Gamma-Aminobutyric Acid Receptor- B (GABABR), Gamma-Aminobutyric Acid Receptor- A (GABAAR), components of voltage gated potassium channel (VGKC) complex, dopamine D2 receptor (D2R)(Nese Sinmaz, 2015). Autoimmune N-methyl-D-aspartate (NMDA) receptor encephalitis has been of particular interest to psychiatrists with it being the most studied paraneoplastic syndrome, as 77% of affected patients first present to psychiatry with a broad range of symptoms (Jennifer L.Kruse, 2015). Very few and limited data have been found on the association between voltage gated calcium channel (P/Q type) and psychosis. In this poster, we describe a case of an individual presenting with late onset first episode of psychosis, with positive P/Q channel antibodies. <h3>Methods</h3> Previous studies and reviews over the past 10 years were reviewed using PubMed, Medline and Google Scholar. Search terms were "psychosis", "autoimmune psychosis", "autoantibodies and psychosis" "geriatric psychosis" "P/Q-type Calcium channel" "Paraneoplastic syndrome" "very late onset psychosis". We reviewed available literature with regards to first episode of psychosis in old age and possible association with P/Q-type voltage gated calcium channel. <h3>Results</h3> DiscussionVery late onset psychosis is delineated as onset of psychosis after the age of 60 years (Howard, 2000). Prevalence of late life psychosis is 23%, however 60% of new onset psychosis in older individuals are of secondary etiology (Cohen, 2015). Psychosis in the elderly individuals could be primarily due to Very Late Onset Schizophrenia Like Psychosis (VLOSLP) vs secondary causes (Delirium, Dementia, Drugs/illicit substances/toxin, Medical conditions). In the discussed case, the patient presented with first episode of psychosis at the age of 70. The extensive workup was positive for P/Q-type Calcium channel binding antibody. Per literature review, the positive predictive value for an autoimmune neurological diagnosis (Lambert-Eaton syndrome or diverse encephalomyeloneuropathic phenotypes) among patients with positive values for P/Q -type calcium channel antibodies < 0.10 nM is 19%. The positive predictive value for a cancer diagnosis (diverse types) among patients positive for P/Q-type calcium channel antibody is 21%; approximately 18% are historical neoplasms, and 3% are detected prospectively (Zalewski NL, 2016). A spectrum of psychiatric autoimmunity beyond NMDA-R IgG is still under-recognized (Jennifer L.Kruse, 2015). In a retrospective case control study conducted by Dr. Jennifer L.Kruse in Mayo clinic, out of the 213 adult psychiatric inpatient 3 patients were found to have positive P/Q-type Calcium channel, who manifested with delusional parasitosis, mood disorder with psychotic features, and Major Depressive Disorder with Psychotic features (Jennifer L.Kruse, 2015). Another international case study found genetic association between voltage gated Calcium channel and Schizophrenia (Wen Li1, 2018). While these studies indicate the potential association between voltage gated Calcium channel and psychosis, limited case studies and research could be found on the association, extent and elaboration of the aforementioned. <h3>Conclusions</h3> While there is progressively enriched literature on psychosis due to Paraneoplastic syndrome, specifically Anti NMDA receptor encephalitis, there is not much mention of correlation between P/Q-type calcium channel binding antibodies and psychosis. Cases with rare presentations as above warrant elaborate workup. Along with the abovementioned etiologies, given the increased incidence of psychosis due to autoimmune antibodies, addition of full autoimmune antibody panel should be considered. Shared clinical experience, research and prospective clinical studies will direct developing guidelines for evaluation, management and prognostic indicators of Paraneoplastic Syndromes with Neuropsychiatric symptoms, particularly due to autoimmunity against voltage gated calcium channel (P/Q-type). <h3>This research was funded by</h3> There are no financial conflicts of interest to disclose

The challenges of the family caregivers in caring of late onset schizophrenia and very late onset schizophrenia‐like psychosis: Caregiver risk of burden and neurodegenerative disease

AbstractBackgroundThe challenges of taking care family member with Late Onset Schizophrenia (LOS) and Very Late Onset Schizophrenia Like Psychosis (VLOSLP) were enormous, include physiological and phycological factors. Family caregiver who taking care patients with schizophrenia experience emotional, physical, and financial challenges and lead of the caring process include decision of the patient’s institutionalizations. This study to investigate the burden experienced by family caregiver taking care to their family member with Late Onset Schizophrenia (LOS) and Very Late Onset Schizophrenia Like Psychosis (VLOSLP). Moreover, the impact of their challenges of the caring were maintain the FCG emotional wellbeing and how they cope of family caregivers’ strategies for the challenges.MethodThis study was cross ‐sectional, descriptive and correlational study. a total of 172 of Dyad FCG were recruited. the research instrument included the Revised Memory Behavior Checklist (RMBC), The Zarid Burden Interview (ZBI), and the Brief Psychiatric Rating Scale (BPRS). Descriptive study, Independent sample t‐test correlation and one‐way ANOVA were use to examined.ResultThe results indicated of more than 76% FCG were burdened and 29% exhibited Dementia. There was positive correlation of FCG Burden with patients Onset (Beta =1.27, p =&lt;.01), FCG sex, Income (Beta =1.31, p =&lt;.01), and level education (Beta =1.28, p =&lt;.01). There was statistically positive correlation of FCG high burden with the level cognitive of FCG (Beta =1.32, p =&lt;.01).ConclusionThe findings improve our understanding about burden and emotional wellbeing in taking care of major schizophrenic with Late Onset Schizophrenia (LOS) and Very Late Onset Schizophrenia Like Psychosis (VLOSLP) especially for women might need a management for their cope with their own feelings. The findings of the study might benefit for health professional to plan the strategies focusing on help challenges of the family caregivers especially for women. the lesson learner from the FCG of LOS might be used to improve the caregiving strategies on patients with VLOSLP.

Brain Atrophy in First-Episode Psychosis of the Elderly Is Associated With Cognitive Decline.

Objective: To study brain atrophy and cognitive decline in elderly patients with first-episode psychosis (FEP).Methods: Elderly patients aged ≥ 60 years with FEP and onset of psychotic symptoms of ≤ 1 year remitted to the Helsinki University Hospital from December 2009 to December 2011 were included in the study. Diagnoses were made using DSM-IV-TR criteria. All patients had a brain scan, magnetic resonance imaging, or computed tomography. Cognitive performance was assessed using the Consortium to Establish a Registry for Alzheimer`s Disease cognitive test battery.Results: Of the 85 patients with FEP, 18 had very late-onset schizophrenia-like psychosis (VLOSP), 20 had delusional psychosis, 12 had depressive psychosis, and 35 had psychosis due to a general medical condition. Fifteen of the patients had an earlier history of schizophrenia not known at the time of admittance. These patients were analyzed separately. A vast majority of the FEP patients in all diagnostic groups exhibited signs of cortical atrophy, which was associated with early stage cognitive decline. Multivariate analyses showed that brain atrophy was associated with a decline in Mini-Mental State Examination, Clock Drawing Test, and verbal fluency scores in FEP patients.Conclusions: Brain atrophy is a frequent finding in elderly FEP patients and is associated with cognitive decline. Elderly patients with FEP should always undergo brain atrophy and cognition screening, as they may constitute an etiologic factor in such patients.

A Case Series of Very Late-onset Schizophrenia-like Psychosis: Is It a Dimension of Dementia?

Emerging research has shown that there may be a subset of patients who develop a first-break psychosis later in life when they are over 60 years of age. Very late-onset schizophrenia-like psychosis (VLOSLP) differs from early-onset schizophrenia in a few very important ways that lead us to believe that there may be a distinct pathologic process involved. We present 4 cases of females with psychotic symptoms that first appeared after the patients were 60 years of age. We conducted a literature review and found that our older adult psychiatric unit is not alone in struggling with diagnoses for these individuals. Some of these patients have a disease that will progress to a neurocognitive disorder, but a large group of others will remain cognitively intact. Fortunately, the treatment for both processes is very similar, but studies have shown that patients with VLOSLP will need significantly lower doses of antipsychotics compared with those with early-onset schizophrenia. It remains unclear if VLOSLP is a unique disorder, a prodrome to dementia, or a different condition that is not yet understood. Further research is needed to develop comprehensive treatment for patients with VLOSLP.

Association between risk of dementia and very late-onset schizophrenia-like psychosis: a Swedish population-based cohort study.

Although the incidence of psychotic disorders among older people is substantial, little is known about the association with subsequent dementia. We aimed to examine the rate of dementia diagnosis in individuals with very late-onset schizophrenia-like psychosis (VLOSLP) compared to those without VLOSLP. Using Swedish population register data, we established a cohort of 15 409 participants with VLOSLP matched by age and calendar period to 154 090 individuals without VLOSLP. Participants were born between 1920 and 1949 and followed from their date of first International Classification of Diseases [ICD], Revisions 8-10 (ICD-8/9/10) non-affective psychotic disorder diagnosis after age 60 years old (or the same date for matched participants) until the end of follow-up (30th December 2011), emigration, death, or first recorded ICD-8/9/10 dementia diagnosis. We found a substantially higher rate of dementia in individuals with VLOSLP [hazard ratio (HR): 4.22, 95% confidence interval (95% CI) 4.05-4.41]. Median time-to-dementia-diagnosis was 75% shorter in those with VLOSLP (time ratio: 0.25, 95% CI 0.24-0.26). This association was strongest in the first year following VLOSLP diagnosis, and attenuated over time, although dementia rates remained higher in participants with VLOSLP for up to 20 years of follow-up. This association remained after accounting for potential misdiagnosis (2-year washout HR: 2.22, 95% CI 2.10-2.36), ascertainment bias (HR: 2.89, 95% CI 2.75-3.04), and differing mortality patterns between groups (subdistribution HR: 2.89, 95% CI 2.77-3.03). Our findings demonstrate that individuals with VLOSLP represent a high-risk group for subsequent dementia. This may be due to early prodromal changes for some individuals, highlighting the importance of ongoing symptom monitoring in people with VLOSLP.

457 - VERY LATE-ONSET SCHIZOPHRENIA-LIKE PSYCHOSIS… A DIAGNOSTIC DILEMMA…

Background:The nosology and etiological underpinnings of very late -onset schizophrenia-like psychosis (VLOSLP) have remained controversial. This case report highlights its diagnostic complexity.Case report:A 64-year-old woman, with a previous history of hypertension, diabetes, mild cognitive decline, right grade-4 hemiparesis as sequelae of an ischemic-stroke (three years before), started persecutory and partition delusions. After six months, the delusions were accompanied by complex visual hallucinations (scenic, lilliputian and holocampine), elementary auditory, tactile, olfactory, and gustatory hallucinations, causing a profound daily life impact, consequently she was hospitalized. Neither negative symptoms nor formal thought disorders were present. Electroencephalography and laboratorial evaluations were unremarkable (including thyroid function, folic acid, cyanocobalamin, infectious serologies and anti-gliadin/transglutaminase antibodies). Neuroimaging displayed subcortical microvascular lesions in the left centrum semiovale, bilateral thalamic and basal ganglia lacunes. Neuropsychological examination revealed mild/moderate impairment in working-memory, sustained-attention, executive functions, abstract thinking, and visuospatial abilities. Mini-mental state examination (MMSE) scored 20/30. Clozapine was started. As psychotic symptoms ameliorated cognitive deficits also improved (MMSE score: 25/30). She was discharged with residual symptoms.Discussion:Late-life psychosis implies a thorough investigation, bringing about challenges in diagnosis. Several medical causes, including neuroinflammatory/immunologic, were ruled out. This two-stage progression, with partition delusions and multimodal hallucinations, in the absence of formal thought disorder and negative symptoms is typical of VLOSP. It is arguable to ascribe our patient’s psychosis to a previous vascular dementia or to VLOSLP. Almost half of VLOSLP patients may develop dementia. It is still debatable whether this propensity is a true characteristic of VLOPSL or reflects an initial misdiagnosis. Some neuropathological studies suggest a restricted limbic tauopathy underlying VLOSP. Notwithstanding, cognitive impairment is common in VLOSLP, including in those patients who do not develop dementia. Neuroimaging studies evidence that lacunar infarction in the basal ganglia alongside chronic white matter small vessels ischemic disease, may underlie the pathophysiology of psychosis via a disruption in the frontal-subcortical pathways. Nevertheless, cases of post-stroke psychosis usually resolve in few months. In conclusion, the neurobiological underpinnings of VLOSLP are complex and multifaceted. More systematized studies using biomarkers and neuroimaging are needed so clinicians can perform a more accurate diagnosis of VLOSLP.

Risk of dementia and death in very-late-onset schizophrenia-like psychosis: A national cohort study

Knowledge is limited regarding the risks of death and dementia in very-late onset schizophrenia-like psychosis (VLOS). This study aims to scrutinize the associations between VLOS with the risks of death and dementia. Based on a prospective Israeli cohort study with national coverage, 94,120 persons without dementia or schizophrenia diagnoses aged 60 to 90 in 2012 were followed-up for the risks of dementia or death from 2013 to 2017. VLOS was classified as present from the age of the first ICD-9 diagnosis during follow-up, otherwise as absent. Hazard ratios (HR) with confidence intervals (95% CI) were computed with survival models to quantify the associations between VLOS and the risks of death and dementia, without and with adjustment for confounding. Nine sensitivity analyses were computed to examine the robustness of the results. The group with VLOS, compared to the group without, had higher death (n = 61, 18.5% vs. n = 7028, 7.5%, respectively) and dementia (n = 64, 19.5% vs. n = 5962, 6.4%, respectively) rates. In the primary analysis, the group with VLOS compared to the group without had increased risks of death (unadjusted HR = 3.10, 95% CI = 2.36, 4.06, P < .001; adjusted HR = 2.89, 95% CI = 2.15, 3.89; P < .001) and dementia (unadjusted HR = 3.81, 95% CI = 2.90, 4.99, P < .001; adjusted HR = 2.67, 95% CI = 1.82, 3.91; P < .001). The results remained statistically significant (P < .05) in all sensitivity analyses, including among persons without antipsychotic medication. The results may support notions of increased dementia risk and accelerated aging in VLOS, or that VLOS is a prodromal state of dementia.

A CASE OF VERY-LATE-ONSET SCHIZOPHRENIA-LIKE PSYCHOSIS, AN UNDER-RECOGNIZED AND DISTINCT SYNDROME IN THE GERIATRIC POPULATION

Introduction Schizophrenia is classically viewed as a neurodevelopmental disorder that manifests at an early age. However, geriatric presentations of schizophrenia-like illness have been described, suggesting a distinct syndrome and warranting a diagnosis of very-late-onset schizophrenia-like psychosis (VLOSLP). Methods A case from an acute geriatric psychiatry unit at an academic hospital is reported. Results Ms. L was a 76-year-old single Barbadian woman with no prior psychiatric or medical history who presented for inpatient evaluation of persecutory delusions and auditory hallucinations in the context of increasing paranoid behavior over the past year. She believed her neighbors were placing recording devices in her home, stealing money from her bank account, trying to deport her, and take over her apartment. For two months, she had been hearing them talk about her and could also hear Donald Trump telling her she'd be deported. Her family history was significant for a grandmother who had similar new onset of delusions and hallucinations at age 80. On exam, the patient was pleasant, cooperative, euthymic, linear, and alert and fully oriented. MMSE and MOCA performed on admission were both 29/30. Medical workup of psychosis was unrevealing and there was no recent medication or substance use. Her functional impairment due to the new symptoms was limited to slightly reduced sleep and eating (due to fear of poisoning by neighbors); she otherwise had maintained her ADLs, IADLs, and a busy social calendar with multiple volunteer activities. Conclusions The case of Ms. L illustrates a rare presentation of first episode of psychosis at advanced age with relative sparing of cognitive and functional status. This syndrome has been called very-late-onset schizophrenia-like psychosis. The poster will describe the features of this distinct syndrome and advocate for its inclusion in future diagnostic manuals. This research was funded by none

The Incidence of Nonaffective, Nonorganic Psychotic Disorders in Older People: A Population-based Cohort Study of 3 Million People in Sweden.

BackgroundThere are limited data on the epidemiology of very late-onset schizophrenia-like psychosis (VLOSLP) and how this relates to potential risk factors including migration, sensory impairment, traumatic life events, and social isolation. MethodsWe followed up a cohort of 3 007 378 people living in Sweden, born 1920–1949, from their 60th birthday (earliest: January 15, 1980) until December 30 2011, emigration, death, or first recorded diagnosis of nonaffective psychosis. We examined VLOSLP incidence by age, sex, region of origin, income, partner or child death, birth period, and sensory impairments. ResultsWe identified 14 977 cases and an overall incidence of 37.7 per 100 000 person-years at-risk (95% CI = 37.1–38.3), with evidence that rates increased more sharply with age for women (likelihood ratio test: χ2(6) = 31.56, P < .001). After adjustment for confounders, rates of VLOSLP were higher among migrants from Africa (hazard ratio [HR] = 2.0, 95% CI = 1.4–2.7), North America (HR = 1.4, 95% CI = 1.0–1.9, P = .04), Europe (HR = 1.3, 95% CI = 1.2–1.4), Russian-Baltic regions (HR = 1.6, 95% CI = 1.4–1.9), and Finland (HR = 1.6, 95% CI = 1.5–1.7). VLOSLP risk was highest for those in the lowest income quartile (HR = 3.1, 95% CI = 2.9–3.3). Rates were raised in those whose partner died 2 years before cohort exit (HR = 1.1, 95% CI = 1.0–1.3, P = .02) or whose child died in infancy (HR = 1.2, 95% CI = 1.0–1.4, P = .05), those without a partner (HR = 1.9, 95% CI = 1.8–1.9) or children (HR = 2.4, 95% CI = 2.3–2.5), and those whose child had a psychotic disorder (HR = 2.4, 95% CI = 2.2–2.6). InterpretationWe identified a substantial burden of psychosis incidence in old age, with a higher preponderance in women and most migrant groups. Life course exposure to environmental factors including markers of deprivation, isolation, and adversity were associated with VLOSLP risk.

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.

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. 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. 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. 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.

S134. THE INCIDENCE OF PSYCHOSIS IN OLDER PEOPLE: A SWEDISH POPULATION-BASED COHORT STUDY

BackgroundPeople aged 65 and above have consistently been omitted from research on the epidemiology of psychotic disorders. Correspondingly, little is known about the incidence of very late-onset schizophrenia-like psychosis (VLOSLP). We aimed to characterise the incidence of VLOSLP in a Swedish population cohort, including how incidence varied by age, sex, migration, deprivation, traumatic life events, and social isolation.MethodsWe conducted a Swedish population-based cohort study to examine the incidence of VLOSLP by potential environmental risk factors. The cohort, born in 1920–1949 and living in Sweden, were followed up from age 60 until the end of follow-up (30th December 2011), emigration, death, or diagnosis with a non-affective psychotic disorder. We used Cox regression to obtain hazard ratios and 95% confidence intervals for VLOSLP by age, sex, migration, disposable income at age 60, and the experience of the death of a partner or child, adjusting for potential confounders.ResultsIn a cohort of 2,955,796 people, we identified 14,825 cases with VLOSLP, with an overall incidence rate of 38.1 (95% CI: 37.5 – 38.7) per 100,000 person-years at-risk. Rates were higher amongst migrants from North America (HR=1.4, 95% CI=1.0–1.9), Europe (HR=1.5, 95% CI=1.4–1.6), Russian-Baltic regions (HR=1.7, 95% CI=1.4–2) and Africa (HR=2.0, 95% CI=1.4–2.7) compared to Swedish-born, with a lower rate in migrants from the Middle East (HR=0.7, 95% CI=0.5–1.0). Rates were higher in those with the lowest income (HR=3.1, 95% CI=2.9–3.3), who experienced the death of a partner (HR=1.1, 95% CI=1.0–1.2), death of a child in infancy (HR=1.2, 95% CI=1.0–1.5), and those without a partner (HR=1.8, 95% CI=1.8–1.9) or children (HR=2.6, 95% CI=2.5–2.7).DiscussionIn this large, national cohort study we identified several potential risk factors for developing psychosis later in life, including migration, deprivation, social isolation and traumatic life events. This may have important implications for our understanding of the aetiology of VLOSLP and could help to inform public mental health and service planning.