Cerebral Amyloid Angiopathy in Patients with Cognitive Impairment -Cerebrospinal Fluid Biomarkers.

INTRODUCTION: Cerebral amyloid angiopathy (CAA) is characterized by amyloid ß (Aß) deposition in brain vessels, leading to hemorrhagic phenomena and cognitive impairment. Magnetic resonance imaging (MRI)-based criteria allow a diagnosis of probable CAA in vivo, but such a diagnosis cannot predict the eventual development of CAA. METHODS: We conducted a retrospective cohort study of 464 patients with cognitive disorders whose data were included in a brain health biobank. De-identified parameters including sex, age, cognitive score, APOE status and cerebrospinal fluid (CSF) levels of Aß 1-40, Aß 1-42, phosphorylated tau, and total tau were assessed in those with and without CAA. Odds ratios (ORs) and 95% confidence intervals (CIs) were determined. RESULTS: CAA was present in 53 of 464 (11.5%) patients. P-tau level was significantly higher in those with CAA (115 vs 84.3 pg/ml p=0.038). In univariate analyses, the risk of developing CAA was higher with increased age (OR, 1.036; 95% CI: 1.008, 1.064; p = 0.011) and decreased CSF level of Aß 1-40 (OR, 0.685; 95% CI: 0.534, 0.878; p = 0.003). In multivariate analyses, the risk of CAA remained higher with a decreased CSF level of Aß 1-40 (OR, 0.681; 95% CI: 0.531, 0.874; p = 0.003). CONCLUSION: These findings suggest that Aß 1-40 levels in the CSF might be a useful molecular biomarker of CAA in patients with dementia.

Pimavanserin Treatment for Psychosis in Patients with Dementia with Lewy Bodies: A Case Series.

BACKGROUND Many patients with dementia with Lewy bodies (DLB) experience cholinesterase inhibitor- and antipsychotic-resistant psychosis. The new second-generation antipsychotic pimavanserin has been used with some success in the treatment of psychosis in other forms of dementia, including Alzheimer disease and Parkinson disease dementia. It is possible that pimavanserin may also be useful in the treatment of psychosis in DLB. We sought to describe the disease course and treatment of psychosis in 4 patients with DLB who were prescribed pimavanserin after other medications failed to reduce the frequency or severity of hallucinations and delusions. CASE REPORT This is a case series of 4 male patients (ages 56 to 74 at the beginning of the reports) who developed DLB and psychosis (eg, visual illusions, visual and olfactory hallucinations, and paranoid delusions). All 4 patients were prescribed cholinesterase inhibitors (eg, donepezil or rivastigmine) prior to pimavanserin, and only 1 patient experienced improved psychosis while on cholinesterase inhibitors. All 3 patients who were prescribed first-generation antipsychotics (eg, haloperidol) or traditional second-generation antipsychotics (eg, olanzapine, risperidone, or quetiapine) experienced initial or lasting side effects with no improvement of psychosis. Conversely, all 4 patients tolerated pimavanserin well, and 3 of the 4 patients experienced significant improvement of psychosis (eg, fewer hallucinations, fewer delusions, reduced paranoia, and/or reduced distress or agitation related to hallucinations and delusions) when prescribed pimavanserin. CONCLUSIONS This case series suggests that pimavanserin is tolerable in older males with DLB and that it may be useful for the reduction of distressful hallucinations, delusions, and paranoia in patients with DLB.

IPA and WPA-SOAP position statement on deprivation of liberty of older persons with mental health conditions.

In recognition of the challenges faced by older persons deprived of their liberty, a call was made for input into the 2022 report to the United Nations Human Rights Council (HRC) on older persons. This Position Statement outlines the views of two global organizations, the International Psychogeriatric Association (IPA) and the World Psychiatric Association Section of Old Age Psychiatry (WPA-SOAP), working together to provide rights and dignity-based mental health services to older persons and it was sent to the Independent Expert on the enjoyment of all human rights by older persons at HRC.

Advances in Management of Psychosis in Neurodegenerative Diseases.

PURPOSE OF THE REVIEW: Psychosis is broadly defined as a disengagement from reality. It describes syndromes that impair both thought content and thought process. Psychosis negatively impacts an individual's quality of life, in addition to the families caring for them. Psychosis with different types of hallucinations and delusions occurs in the context of delirium. Neuropsychiatric symptoms (NPS) are almost universal in the course of common neurodegenerative disorders (NDD) like Alzheimer's disease (AD) or Parkinson's disease (PD). In this paper, the authors took an effort to characterize AD and PD psychosis with a special focus on the most diagnostically reliable features. Effectiveness and limitations of pharmacological interventions are discussed. RECENT FINDINGS: Consensus diagnostic criteria have evolved for psychosis secondary to AD as well as psychosis in PD. Psychotropic medications can be effective in the treatment of NPS in NDD; however, clinicians must be mindful of the side effects. There is a consensus on benefit of initiating any acetylcholinesterase inhibitor (ACHI: donepezil, rivastigmine, and galantamine) as a first line of treatment for psychosis in AD, as it may reduce and/or avoid the need for the use antipsychotics. Pimavanserin, a selective-serotonin inverse agonist that preferentially targets 5-HT2A receptors, while avoiding activity at dopamine and other receptors commonly targeted by antipsychotics had recently been approved by FDA to treat hallucinations and delusions in PD. Quetiapine is widely prescribed for the treatment of psychosis in different NDD, but the data remains equivocal. Psychosis with different types of hallucinations and delusions may occur in the context of delirium and is almost universal as a neuropsychiatric symptom in the course of PD and AD. Currently, pimavanserin remains the only pharmacologic agent approved for treatment of psychosis in PD. In cases of other NPS in other than Parkinson's diseases, atypical antipsychotics are commonly used off-label. More research is greatly needed to advance this field and address NPS especially psychosis in geriatric population.

Cognitive functions, apolipoprotein E genotype and hormonal replacement therapy of postmenopausal women.

OBJECTIVE: The results of many studies revealed that estrogen plus progestogen therapy (EPT) may modify dementia development risk in relation to the apolipoprotein E gene (APOE) polymorphisms. However, the mechanism and subsequently clinical importance of such an effect are still unexplained. The objective of this study was to explore the influence of EPT on cognitive functioning of women in their postmenopausal life in relation to APOE polymorphism. METHODS: The group of 214 women was recruited (106 out of this group with EPT) to the study. The inclusion criteria were: minimum two years after the last menstruation, FSH concentration over 30 U/ml and no dementia signs on Montreal Cognitive Assessment (MoCA). Computerized battery of Central Nervous System Vital Signs (CNS VS) test was used to diagnostic cognitive functions. APOE genotype was performed by multiplex PCR. Statistical analysis was performed using two-way analysis of variance in STATISTICA software. RESULTS & CONCLUSION: The women after menopause have reduced neurocognitive index (NCI) and cognitive functions. NCI and all studied cognitive functions of the patients depended significantly on APOE polymorphisms. The presence of APOE4 corresponded with decreased cognitive functions as opposed to APOE2 which was present in women with better level of cognitive functions. Constantly using EPT correlated with three cognitive functions: memory, verbal memory and processing speed, which were significantly worse for women taking EPT than not taking ones. The interaction between APOE polymorphisms and EPT application was significant only for processing speed. EPT applying women with ε2/ε3 and ε4 obtained better scores in processing speed than women not taking EPT with these APOE polymorphisms. The opposite situation concerned women with ε3/ε3, women taking EPT achieved worse processing scores in comparison with those not taking EPT. It should be noted that APOE polymorphism assessment may be a factor in predicting the effect of EPT on cognitive functioning in postmenopausal period.