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Background: Agitation and aggression are common in patients with Alzheimer’s disease and related dementias and pose a significant burden on patients, caregivers, and the healthcare systems. Guidelines recommend personalized behavioral interventions as the first-line treatment; however, these interventions are often underutilized. The Standardizing Care for Neuropsychiatric Symptoms and Quality of Life in Dementia (StaN) study (ClinicalTrials.gov Identifier # NCT0367220) is a multisite randomized controlled trial comparing an Integrated Care Pathway, that includes a sequential pharmacological algorithm and structured behavioral interventions, with treatment-as-usual to treat agitation in dementia in long-term care and inpatient settings. Objective: To describe the rationale and design of structured behavioral interventions in the StaN study. Methods: Structured behavioral interventions are designed and implemented based on the following considerations: 1) personalization, 2) evidence base, 3) dose and duration, 4) measurement-based care, and 5) environmental factors and feasibility. Results: The process to design behavioral interventions for each individual starts with a comprehensive assessment, followed by personalized, evidence-based interventions delivered in a standardized manner with ongoing monitoring of global clinical status. Measurement-based care is used to tailor the interventions and integrate them with pharmacotherapy. Conclusion: Individualized behavioral interventions in patients with dementia may be challenging to design and implement. Here we describe a process to design and implement individualized and structured behavioral interventions in the context of a multisite trial in long-term care and inpatient settings. This process can inform the design of behavioral interventions in future trials and in clinical settings for the treatment of agitation in dementia.

To explore how processing lexicality may change with aging and in the presence of Alzheimer’s disease (AD), we conducted two experiments investigating lexicality judgements using an on-line behavioural psycholinguistic methodology and electrophysiological/event-related potential (ERP) methods; oddball lexical decision tasks. Results from these lexical decision tasks showed that while those with AD show similar rates of accuracy for their lexical decision as compared older adults (OA), they are particularly slowed when making judgements for pseudowords. Our results from the ERP tasks also showed that the two groups behaved differently with regard to elicitation of the P3 ERP response, which indicates differences in how these two groups form lexical categories. The pattern of ERP responses suggests that older adults are sensitive to the orthography/phonology of the stimuli during the course of lexical processing as compared to participants with AD who show less sensitivity to orthographic/phonological cues. Additionally, the ERP P3 amplitude results suggest further linguistically related differences between healthy older adults and those with AD, and highlight the importance and usefulness of combining behavioural psycholinguistic and ERP methodologies.

Background Major prevention trials for Alzheimer’s disease (AD) are now focusing on multidomain lifestyle interventions. However, the exact combination of behavioral factors related to AD pathology remains unclear. In 2 cohorts of cognitively unimpaired individuals at risk of AD, we examined which combinations of personality traits, neuropsychiatric symptoms, and cognitive lifestyle (years of education or lifetime cognitive activity) related to the pathological hallmarks of AD, amyloid-β, and tau deposits. Methods A total of 115 older adults with a parental or multiple-sibling family history of sporadic AD (PREVENT-AD [PRe-symptomatic EValuation of Experimental or Novel Treatments for AD] cohort) underwent amyloid and tau positron emission tomography and answered several questionnaires related to behavioral attributes. Separately, we studied 117 mutation carriers from the DIAN (Dominant Inherited Alzheimer Network) study group cohort with amyloid positron emission tomography and behavioral data. Using partial least squares analysis, we identified latent variables relating amyloid or tau pathology with combinations of personality traits, neuropsychiatric symptoms, and cognitive lifestyle. Results In PREVENT-AD, lower neuroticism, neuropsychiatric burden, and higher education were associated with less amyloid deposition (p = .014). Lower neuroticism and neuropsychiatric features, along with higher measures of openness and extraversion, were related to less tau deposition (p = .006). In DIAN, lower neuropsychiatric burden and higher education were also associated with less amyloid (p = .005). The combination of these factors accounted for up to 14% of AD pathology. Conclusions In the preclinical phase of both sporadic and autosomal dominant AD, multiple behavioral features were associated with AD pathology. These results may suggest potential pathways by which multidomain interventions might help delay AD onset or progression.

ObjectiveTo identify the pathophysiologic mechanisms and clinical significance of anosognosia for cognitive decline in mild cognitive impairment.MethodsWe stratified 468 patients with amnestic mild cognitive impairment into intact and impaired awareness groups, determined by the discrepancy between the patient and the informant score on the Everyday Cognition questionnaire. Voxel-based linear regression models evaluated the associations between self-awareness status and baseline β-amyloid load, measured by [18F]florbetapir, and the relationships between awareness status and regional brain glucose metabolism measured by [18F]fluorodeoxyglucose at baseline and at 24-month follow-up. Multivariate logistic regression tested the association of awareness status with conversion from amnestic mild cognitive impairment to dementia.ResultsWe found that participants with impaired awareness had lower [18F]fluorodeoxyglucose uptake and increased [18F]florbetapir uptake in the posterior cingulate cortex at baseline. In addition, impaired awareness in mild cognitive impairment predicted [18F]fluorodeoxyglucose hypometabolism in the posterior cingulate cortex, left basal forebrain, bilateral medial temporal lobes, and right lateral temporal lobe over 24 months. Furthermore, participants with impaired awareness had a nearly 3-fold increase in likelihood of conversion to dementia within a 2-year time frame.ConclusionsOur results suggest that anosognosia is linked to Alzheimer disease pathophysiology in vulnerable structures, and predicts subsequent hypometabolism in the default mode network, accompanied by an increased risk of progression to dementia. This highlights the importance of assessing awareness of cognitive decline in the clinical evaluation and management of individuals with amnestic mild cognitive impairment.

Introduction Dementia is associated with stress, anxiety, and depression in both patients and caregivers. Yoga may be a viable therapeutic modality to address these challenges, as it has been shown to decrease stress and improve anxiety and depressive symptoms in various populations. While there is preliminary data on dyadic exercise interventions for dementia patients and their caregivers, to date no research has examined the effectiveness of a dyadic yoga intervention. Methods We propose an 8-week single arm pilot trial of a dyadic chair yoga intervention for patients and their caregivers (n = 30-40). The primary outcome is perceived stress (Perceived Stress Scale (PSS)), while secondary outcomes include symptoms of depression (Patient Health Questionnaire (PHQ9)) and anxiety (Generalized Anxiety Disorder 7-Item Scale (GAD7)). Exploratory outcomes include caregiver burden (Zarit Burden Inventory (ZBI)), quality of interactions (Dyadic Relationship Scale (DRS)), well-being (12-Item Well-Being Questionnaire (W-BQ12)), mindfulness (Five Facet Mindfulness Questionnaire (FFMQ)), and self-compassion (Short Form of the Self-Compassion Scale (SCS-SF)). Results The protocol of this study will be presented at AAGP 2020 in San Antonio, Texas. Results will be ready by mid-2020. Conclusions We anticipate that this novel dyadic chair yoga intervention will improve stress, as well as depression, anxiety, and other outcomes, in dementia patients and their caregivers. If successful, this study provides crucial pilot data for a larger definitive randomized controlled trial. Future studies can also assess whether this intervention may improve direct and indirect health-care costs. This research was funded by: This low-cost pilot study has received no outside funding.

Background Current pharmacological treatments and psychotherapeutic approaches often have adverse effects or are ineffective in late-life cognitive and mental illnesses. Mind-body interventions offer a holistic approach and are of interest because of potential patient acceptability and scalability. Objective To synthesize current evidence on mind-body interventions in treating or preventing mental illnesses and cognitive disorders in older adults. Search Strategy A search was conducted using Ovid MEDLINE, EMBASE, and PsycINFO articles published from 1993 to 2017. Selection Criteria 1) Randomized controlled trials, 2) involving older adults (>60 years old), 3) suffering from mental illness or cognitive decline, 4) comparing mind-body interventions with a control group. Mind-body interventions included: imagery, meditation, prayer, autogenic training, tai chi & variants, and yoga. Control group included: health education, other non-pharmacological interventions, treatment as usual, or no treatment at all. Data Collection and Analysis Data included number of patients, age, psychiatric diagnoses, type of intervention, frequency andduration, control conditions, outcomes measures and treatment results. Results 3916 articles were reviewed and ten met inclusion criteria. Six were on Tai Chi and four assessed meditation-based therapies. Clinically significant improvement in depressive and anxiety symptoms were reported, as well as improvement insomedomains of cognition and reduced risk of cognitive deterioration. Conclusion There is increasing evidence that mind-body interventions may potentially be useful in the treatment or prevention of geriatric mental illnesses and cognitive disorders. There are important methodological limitations of the current literature such as small sample sizes, heterogeneous study populations, and varying clinical outcomes.

Background: Both subjective cognitive decline (SCD) and a family history of Alzheimer's disease (AD) portend risk of brain abnormalities and progression to dementia. Posterior default mode network (pDMN) connectivity is altered early in the course of AD. It is unclear whether SCD predicts similar outcomes in cognitively normal individuals with a family history of AD. Methods: We studied 124 asymptomatic individuals with a family history of AD (age 64 ± 5 years). Participants were categorized as having SCD if they reported that their memory was becoming worse (SCD+). We used extensive neuropsychological assessment to investigate five different cognitive domain performances at baseline (n = 124) and 1 year later (n = 59). We assessed interconnectivity among three a priori defined ROIs: pDMN, anterior ventral DMN, medial temporal memory system (MTMS), and the connectivity of each with the rest of brain. Results: Sixty-eight (55%) participants reported SCD. Baseline cognitive performance was comparable between groups (all false discovery rate-adjusted p values >.05). At follow-up, immediate and delayed memory improved across groups, but the improvement in immediate memory was reduced in SCD+ compared with SCD− (all false discovery rate–adjusted p values −, SCD+ subjects showed increased pDMN–MTMS connectivity (false discovery rate–adjusted p

Neighbourhood density (N) has been shown to influence how lexical stimuli are accessed. In young adults, a large N is facilitatory for words but inhibitory for pseudowords in English. While there is a paucity of studies probing N as people age, results to date point towards changes in lexical processing that occur with aging. We are not aware of any studies that have sought to investigate N in Alzheimer’s disease (AD) in English. Results from the lexical decision task reported here support previous N findings for young adults. However, older adults and those with AD showed a different pattern of performance. Both were slower to respond to and made more errors to high versus low N pseudowords but, unlike young adults, older adult groups showed a decrease in sensitivity to N for words. Results suggest that the aging process may change how N is processed; older individuals are no longer as sensitive to N and this appears to be further altered by AD. In the context of the multiple read-out model of lexical processing, this change may be due to a longer time required to activate lexical neighbours which, in turn, results in differential N effects for words and pseudowords.

Cognitive reserve could be defined as the accumulation of experiences, abilities, knowledge and changes that occur throughout the lifespan. One of the most difficult changes in life is the experience of emigrating to a foreign country.The present investigation aimed to compare the cognitive reserve of two paired groups of elderly: Italians living in Italy and Italians who in adult age (around 20 years) emigrated to Montreal. Both groups attended the same years of school, in Italy.Cognitive reserve was measured in the two groups by a structured and standardised questionnaire, the cognitive reserve questionnaire.Cognitive reserve showed to be significantly higher in the Italian-Canadian individuals (i.e. Italians who emigrated).Emigration might act as an environmental factor that enriches people's lifestyle and reflects itself in the amount of their cognitive reserve.

The exploratory eye movements of patients with schizophrenia reportedly differ from those of patients without schizophrenia and healthy controls. In an attempt to determine whether exploratory eye movements provide valid markers for schizophrenia, the present collaborative study was conducted in six countries to analyze the stability of and variation in the following parameters of exploratory eye movements: the number of eye fixations (NEFs) and mean eye scanning length (MESL) in a retention task; the cognitive search score (CSS) that indicates how frequently the eye focused on each important area of a figure in order to recognize it in a comparison task; and the responsive search score (RSS), which reflects the frequency of eye fixations on each section of a figure in response to questioning in a comparison task. In addition, we investigated the validity of the currently employed discriminant function to extract a common feature of schizophrenia by applying it to the findings of the present study. The exploratory eye movements of 145 patients with schizophrenia, 116 depressed patients and 124 healthy controls at seven WHO collaborative centers in six countries were measured using eye mark recorders during viewing of stationary S-shaped figures in two sequential tasks. The RSSs of patients with schizophrenia were found to be significantly lower than those of depressed patients or healthy controls irrespective of geographical location, with no significant difference existing between the RSSs for depressed patients and those for healthy controls. By inserting the RSS and NEF data for each subject into the formula used to calculate discriminant function, patients with schizophrenia could be discriminated from depressed patients and healthy controls with a sensitivity of 89.0% and a specificity of 86.7%. The RSS is an exploratory eye movement parameter that detected schizophrenia irrespective of culture, race and various other subject variables. Furthermore, it is indicative of the stable, significant difference that exists between subjects with and without schizophrenia. The results of discriminant analysis confirm the previously reported validity of discriminant function.

Recent studies have suggested clinical differences among selective serotonin reuptake inhibitors. In a 12-week randomized, multicenter, double-blind trial, the antidepressant and anxiolytic efficacy of the selective serotonin reuptake inhibitors paroxetine and fluoxetine was compared in patients with moderate to severe depression.A total of 203 patients were randomized to fixed doses (20 mg/day) of paroxetine or fluoxetine for the first six weeks of therapy. From week 7-12, dosing could be adjusted biweekly, as required (paroxetine 20-50 mg/day, and fluoxetine 20-80 mg/day). The mean prescribed doses were paroxetine 25.5 mg/day (range 20.0-40.2 mg/day), and fluoxetine 27.5 mg/day (range 20.0-59.5 mg/day). Emergence of motor nervousness or restlessness was assessed using the ESRS scale for akathisia.Both active treatments demonstrated comparable antidepressant efficacy (HAM-D, CGI). Anxiolytic activity of the two drugs (COVI, STAI, HAM-D) was also comparable. However, paroxetine was found to be superior to fluoxetine on two subscore measures at week 1 of therapy (HAM-D Agitation item, p0.05; Psychic Anxiety item, p0.05), with no differences detected after week 2. The overall incidence of adverse effects was comparable in the two treatment groups. Constipation, dyspepsia, tremor, sweating and abnormal ejaculation were more common in paroxetine-treated subjects, whereas nausea and nervousness were more frequent in fluoxetine-treated patients. Weight loss was more common in the fluoxetine versus paroxetine group (11.88% versus 2.94%, respectively). ESRS scores for akathisia were low throughout the study and showed little change.Differences observed between the two drugs in antianxiety effects were limited to two measures of anxiety among several others.The data indicate that paroxetine and fluoxetine have comparable antidepressant and anxiolytic efficacy. Paroxetine appears to produce an earlier improvement in agitation and psychic anxiety symptoms compared with fluoxetine.

The exploratory eye movements of patients with schizophrenia reportedly differ from those of patients without schizophrenia and healthy controls. In an attempt to determine whether exploratory eye movements provide valid markers for schizophrenia, the present collaborative study was conducted in six countries to analyze the stability of and variation in the following parameters of exploratory eye movements: the number of eye fixations (NEFs) and mean eye scanning length (MESL) in a retention task; the cognitive search score (CSS) that indicates how frequently the eye focused on each important area of a figure in order to recognize it in a comparison task; and the responsive search score (RSS), which reflects the frequency of eye fixations on each section of a figure in response to questioning in a comparison task. In addition, we investigated the validity of the currently employed discriminant function to extract a common feature of schizophrenia by applying it to the findings of the present study. The exploratory eye movements of 145 patients with schizophrenia, 116 depressed patients and 124 healthy controls at seven WHO collaborative centers in six countries were measured using eye mark recorders during viewing of stationary S-shaped figures in two sequential tasks. The RSSs of patients with schizophrenia were found to be significantly lower than those of depressed patients or healthy controls irrespective of geographical location, with no significant difference existing between the RSSs for depressed patients and those for healthy controls. By inserting the RSS and NEF data for each subject into the formula used to calculate discriminant function, patients with schizophrenia could be discriminated from depressed patients and healthy controls with a sensitivity of 89.0% and a specificity of 86.7%. The RSS is an exploratory eye movement parameter that detected schizophrenia irrespective of culture, race and various other subject variables. Furthermore, it is indicative of the stable, significant difference that exists between subjects with and without schizophrenia. The results of discriminant analysis confirm the previously reported validity of discriminant function.

Eighty patients whose tardive dyskinesia (TD) had been assessed two years previously were reevaluated. The majority (66%) showed no change in their TD. An almost equal number improved (18%) and worsened (16%). Patients whose TD improved were younger (P

Bipolar affective disorder arising for the first time in old age (60 years and over) has not been extensively studied. The authors present a prevalence study of mania arising after age 60. Of 217 patients admitted to our unit in a 2-year period, 10 (4.7%) showed symptoms of mania, using the DSM-III criteria. This constitutes 9.3% of 108 affective disorder patients admitted during the same period. An important factor in the precipitation of these attacks was marital discord, leading, in several cases, to separation, even in this age group.

Patients with late-onset psychosis (defined as psychosis requiring hospitalization at age 45 or more, n = 20) were compared with early-onset psychosis patients (defined as psychosis requiring hospitalization at age 25 or less, n = 56) for the prevalence of tardive dyskinesia (TD). Late-onset psychosis patients were found to have significantly more TD (p less than 0.01), which was more severe (p less than 0.05) and developed in a relatively shorter period of neuroleptic treatment (p less than 0.001), than patients with early-onset psychosis. In addition, TD patients (irrespective of early or late onset of neuroleptic treatment) were found to show a preponderance of drug-free periods (p less than 0.01) in their past neuroleptic history, more so than non-TD patients. Our findings indicate that late-onset psychosis should be considered to be a risk factor for the development of TD.

1. 1. A survey of 315 chronic inpatients for the presence of extrapyramidal side effects indicates that 58.7% of the patients had no evidence of extrapyramidal side effects, 28.6% had tardive dyskinesia (TD) alone, 8.9% had pseudoparkinsonism and 3.8% had a combination of both. 2. 2. Women seemed to exhibit more side effects. 3. 3. Aging was another factor associated with a higher risk for the appearance of extrapyramidal side effects. 4. 4. Affective disorder patients carried more risk than patients with schizophrenia. 5. 5. The low prevalence of the combined TD and pseudoparkinsonism may be related to several factors. The possible explanations are explored and discussed. These patients present a therapeutic dilemna.

Thirty-five bipolar outpatients treated with lithium carbonate were followed for up to 5 years with the aim of studying the relation of the lithium ratio (LR) and its predictive value. Only male responders were found to have higher LR than male nonresponders. No difference was found between the mean LR of men and women, as a group. Aging also had no effect on LR. Positive family history of affective disorders was correlated with high LR, irrespective of response.

1. The in vitro autoradiographic distribution of calcium channel antagonist binding sites for 1,4-dihydropyridine and phenylalkylamine has been investigated in rat, guinea pig and human brain. 2. 1,4-dihydropyridine([3H] (+) PN200-110) and phenylalkylamine ([3H] (−) D-888) binding sites are identically distributed in the brain of the three mammalian species studied. 3. High densities of calcium antagonist binding sites are present in brain areas enriched in synaptic contacts such as the hippocampus, cortex and striatum. Low to moderate densities of sites are found in other regions such as the thalamus, hypothalamus and brain stem. 4. These data demonstrate the existence of specific calcium antagonist binding sites in mammalian brain including man. These sites are discretely distributed with highest concentrations present in the hippocampus and cortex. Moreover, the similar distribution of binding sites for [3H](+)PN200-110 and [3H](−) D-188 suggests that 1,4-dihydropyridine and phenylalkylamine bind to the same receptor site complex in mammalian brain.

Among 108 primarily psychiatric outpatients surveyed for tardive dyskinesia (TD), eight (7.4%) developed the disorder by the end of a two-year prospective study. A comparison between the TD patients and a control group (matched for age, sex, duration of neuroleptic treatment, and diagnosis) yielded no confirmed predisposing factor differentiating the two populations. However, age, especially in women, may be important in the development of TD.

1. Neurochemical analyses of the medial frontal cortex in a case of Gerstmann-Straussler syndrome revealed a 52% decrease in choline acetyltransferase. 2. In contrast muscarinic receptors, amino acids, monoamines and somatostatin were unchanged. 3. The monoamine metabolites homovanillic acid and 5-hydroxyindole acetic acid were elevated. 4. These data suggest a selective degeneration of cortical cholinergic pathways, as has been observed in Alzheimer's disease. 5. The cholinergic input to the cortex may well therefore play a role in the cognitive deficit of these 2 forms of dementia.

In a four-segment long-term (greater than or equal to 6 mo) study, patients with schizophrenia received oral haloperidol in single daily doses and subsequently depot intramuscular (IM) haloperidol decanoate q28d. For each route of administration, a period of stabilization was followed by a maintenance period. Dosages for both oral haloperidol and IM haloperidol decanoate were determined on the basis of the patient's past psychiatric history and clinical response during the stabilization period. To characterize the concentration-time profile of the two routes of administration, blood samples were obtained on two separate occasions at steady state during maintenance dosing for each route of administration. Examination of values for cumulative area under the plasma concentration-time curves (AUC) to each sampling time indicated a sustained release of haloperidol from the intramuscularly administered haloperidol decanoate. Dose ranges during maintenance periods were 5-35 mg/d for oral haloperidol (mean, 17 mg/d), and 75-500 mg/28 d for IM haloperidol decanoate (mean, haloperidol decanoate was 243 mg equivalents of haloperidol/28 d). The ratio of long-acting to daily oral doses during maintenance therapy ranged from 9.4:1.0 to 15.0:1.0 (mean, 14.1:1.0). At these ratios, plasma concentration data showed that haloperidol decanoate gave lower values than did oral haloperidol for peak plasma, minimum plasma, and mean steady-state plasma concentrations. The absolute concentration swing was significantly less for decanoate than for the oral drug. Dose-normalized AUC values were compared determine the IM dose of haloperidol decanoate that would have yielded haloperidol plasma concentrations equivalent to those resulting from daily oral administration of haloperidol for 28 days.(ABSTRACT TRUNCATED AT 250 WORDS)