Epidemiology of at-risk alcohol use and associated comorbidities of interest among community-dwelling older adults: a protocol for a systematic review.

INTRODUCTION: There is little epidemiological evidence and knowledge about at-risk alcohol use among community-dwelling older adults and their chronic and acute alcohol-related comorbidities of interest. This systematic review will summarise and examine relevant studies about the epidemiology of at-risk alcohol use and associated comorbidities of interest in this population. METHODS: We will search the following databases, without language or date restrictions, from inception to 31 August 2019: Embase.com, Medline Ovid SP, Pubmed (NOT medline[sb]), CINAHL EBSCO, PsycINFO Ovid SP, Central-Cochrane Library Wiley and Web of Science (Core Collection). Search strategies will be developed in collaboration with a librarian. We will use predefined search terms for alcoholism, epidemiology, the elderly, living place and comorbidities of interest, as well as terms related to the identification of "measurements", "tools" or "instruments" for measuring harm from alcohol use. At-risk status will be determined by the amount of alcohol consumed and any comorbidities of interest associated with at-risk alcohol use, with the latter being documented separately or using an assessment tool for at-risk drinking. We will also examine the bibliographies of all the relevant articles found and search for unpublished studies. We will consider publications in all languages. ETHICS AND DISSEMINATION: No ethical approval is necessary. Results will be presented in national and international conferences on addiction and published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42018099965.

Demographics, Clinical Characteristics, and Therapeutic Approaches among Older Adults Referred to Mobile Psychiatric Crisis Intervention Teams: A Retrospective Study.

BACKGROUND / AIMS: The advent of mobile old age psychiatry intervention teams supports policies maintaining older adults in their habitual living environments, even those who are very old and suffering from acute cognitive and psychiatric impairments. Analyzing sociodemographic data, clinical and health characteristics, reasons for crisis-oriented psychiatric consultations, and other therapeutic suggestions for supporting home- or nursing home-dwelling older adult patients suffering from an onset of a psychiatric crisis. METHODS: Reviews of the medical records and discharge letters of home- or nursing home-dwelling older adults who had undergone a consultation with the Lausanne region's Mobile Old Age Psychiatry Teams (MOAPTs), between May 2016 and December 2017. RESULTS: Of 570 older adult patients referred for consultation with MOAPTs, 333 had medical records and discharge letters eligible for retrospective analysis (59%). The majority of these older adult patients were women aged over 80 years suffering from dementia, mood disorders with and without a risk of suicide, and delirium. Challenging behaviors related to different stages of cognitive impairment were the most important clinical reason for crisis consultations. Nonpharmacological and pharmacological treatments were delivered concurrently in 68% of crisis consultations. CONCLUSION: Appropriate responses by dual nurse-psychiatrist teams using crisis-oriented nonpharmacological and pharmacological interventions decreased hospitalization.

Early changes of blood lipid levels during psychotropic drug treatment as predictors of long-term lipid changes and of new onset dyslipidemia.

BACKGROUND: Cardiovascular diseases and dyslipidemia represent a major health issue in psychiatry. Many psychotropic drugs can induce a rapid and substantial increase of blood lipid levels. OBJECTIVE: This study aimed to determine the potential predictive power of an early change of blood lipid levels during psychotropic treatment on long-term change and on dyslipidemia development. METHODS: Data were obtained from a prospective study including 181 psychiatric patients with metabolic parameters monitored during the first year of treatment and with adherence ascertained. Blood lipid levels (ie, total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], non-high-density lipoprotein cholesterol [non-HDL-C], and fasting triglycerides [TGs]) were measured at baseline and after 1, 3, and/or 12 months of treatment. RESULTS: Receiver-operating characteristic analyses indicated that early (ie, after 1 month of psychotropic treatment) increases (≥5%) for TC, LDL-C, TG, and non-HDL-C and decrease (≥5%) for HDL-C were the best predictors for clinically relevant modifications of blood lipid levels after 3 months of treatment (≥30% TC, ≥40% LDL-C, ≥45% TG, ≥55% non-HDL-C increase, and ≥20% HDL-C decrease; sensitivity 70%-100%, specificity 53%-72%). Predictive powers of these models were confirmed by fitting longitudinal multivariate models in the same cohort (P ≤ .03) as well as in a replication cohort (n = 79; P ≤ .003). Survival models showed significantly higher incidences of new onset dyslipidemia (TC, LDL-C, and non-HDL-C hypercholesterolemia, HDL-C hypocholesterolemia, and hypertriglyceridemia) for patients with early changes of blood lipid levels compared to others (P ≤ .01). CONCLUSION: Early modifications of blood lipid levels following prescription of psychotropic drugs inducing dyslipidemia should therefore raise questions on clinical strategies to control long-term dyslipidemia.

[Behavorial and psychological symptoms in dementia: what alternative to drug?]. / Symptômes comportementaux et psychologiques dans les démences: quelles alternatives à la pharmacothérapie?

Behavioral and psychological symptoms of dementia (BPSD) are frequent and represent a challenge for an optimal care of patients. They must be investigated systematically and if necessary analyzed with specialized teams in the domain of old age Psychiatry so that these disorders are optimally addressed and complications are prevented. A precise analysis of potential causes of BPSD in concertation with both family members and caring team allows clinicians to avoid the use of drugs that may appear to solve the immediate issue but happen to have serious side effects or even toxicity over time.

Cognition and psychopathology in nonagenarians and centenarians living in geriatric nursing homes in Switzerland: a focus on anosognosia.

BACKGROUND: The number of nonagenarians and centenarians is rising dramatically, and many of them live in nursing homes. Very little is known about psychiatric symptoms and cognitive abilities other than memory in this population. This exploratory study focuses on anosognosia and its relationship with common psychiatric and cognitive symptoms. METHODS: Fifty-eight subjects aged 90 years or older were recruited from geriatric nursing homes and divided into five groups according to Mini-Mental State Examination scores. Assessment included the five-word test, executive clock-drawing task, lexical and categorical fluencies, Anosognosia Questionnaire-Dementia, Neuropsychiatric Inventory, and Charlson Comorbidity Index. RESULTS: Subjects had moderate cognitive impairment, with mean ± SD Mini-Mental State Examination being 15.41 ± 7.04. Anosognosia increased with cognitive impairment and was associated with all cognitive domains, as well as with apathy and agitation. Subjects with mild global cognitive decline seemed less anosognosic than subjects with the least or no impairment. Neither anosognosia nor psychopathological features were related to physical conditions. CONCLUSIONS: Anosognosia in oldest-old nursing home residents was mostly mild. It was associated with both cognitive and psychopathological changes, but whether anosognosia is causal to the observed psychopathological features requires further investigation.

Population pharmacokinetic approach to evaluate the effect of CYP2D6, CYP3A, ABCB1, POR and NR1I2 genotypes on donepezil clearance.

AIMS: A large interindividual variability in plasma concentrations has been reported in patients treated with donepezil, the most frequently prescribed antidementia drug. We aimed to evaluate clinical and genetic factors influencing donepezil disposition in a patient population recruited from a naturalistic setting. METHODS: A population pharmacokinetic study was performed including data from 129 older patients treated with donepezil. The patients were genotyped for common polymorphisms in the metabolic enzymes CYP2D6 and CYP3A, in the electron transferring protein POR and the nuclear factor NR1I2 involved in CYP activity and expression, and in the drug transporter ABCB1. RESULTS: The average donepezil clearance was 7.3 l h(-1) with a 30% interindividual variability. Gender markedly influenced donepezil clearance (P < 0.01). Functional alleles of CYP2D6 were identified as unique significant genetic covariate for donepezil clearance (P < 0.01), with poor metabolizers and ultrarapid metabolizers demonstrating, respectively, a 32% slower and a 67% faster donepezil elimination compared with extensive metabolizers. CONCLUSION: The pharmacokinetic parameters of donepezil were well described by the developed population model. Functional alleles of CYP2D6 significantly contributed to the variability in donepezil disposition in the patient population and should be further investigated in the context of individual dose optimization to improve clinical outcome and tolerability of the treatment.

Relationship of CYP2D6, CYP3A, POR, and ABCB1 genotypes with galantamine plasma concentrations.

BACKGROUND: The frequently prescribed antidementia drug galantamine is extensively metabolized by the enzymes cytochrome P450 (CYP) 2D6 and CYP3A and is a substrate of the P-glycoprotein. We aimed to study the relationship between genetic variants influencing the activity of these enzymes and transporters with galantamine steady state plasma concentrations. METHODS: In this naturalistic cross-sectional study, 27 older patients treated with galantamine were included. The patients were genotyped for common polymorphisms in CYP2D6, CYP3A4/5, POR, and ABCB1, and galantamine steady state plasma concentrations were determined. RESULTS: The CYP2D6 genotype seemed to be an important determinant of galantamine pharmacokinetics, with CYP2D6 poor metabolizers presenting 45% and 61% higher dose-adjusted galantamine plasma concentrations than heterozygous and homozygous CYP2D6 extensive metabolizers (median 2.9 versus 2.0 ng/mL · mg, P = 0.025, and 1.8 ng/mL · mg, P = 0.004), respectively. CONCLUSIONS: The CYP2D6 genotype significantly influenced galantamine plasma concentrations. The influence of CYP2D6 polymorphisms on the treatment efficacy and tolerability should be further investigated.

Population pharmacokinetic study of memantine: effects of clinical and genetic factors.

BACKGROUND AND OBJECTIVE: Memantine, a frequently prescribed anti-dementia drug, is mainly eliminated unchanged by the kidneys, partly via tubular secretion. Considerable inter-individual variability in plasma concentrations has been reported. We aimed to investigate clinical and genetic factors influencing memantine disposition. METHODS: A population pharmacokinetic study was performed including data from 108 patients recruited in a naturalistic setting. Patients were genotyped for common polymorphisms in renal cation transporters (SLC22A1/2/5, SLC47A1, ABCB1) and nuclear receptors (NR1I2, NR1I3, RXR, PPAR) involved in transporter expression. RESULTS: The average clearance was 5.2 L/h with a 27 % inter-individual variability (percentage coefficient of variation). Glomerular filtration rate (p = 0.007) and sex (p = 0.001) markedly influenced memantine clearance. NR1I2 rs1523130 was identified as the unique significant genetic covariate for memantine clearance (p = 0.006), with carriers of the NR1I2 rs1523130 CT/TT genotypes presenting a 16 % slower memantine elimination than carriers of the CC genotype. CONCLUSION: The better understanding of inter-individual variability of memantine disposition might be beneficial in the context of individual dose optimization.

Personality traits, cognition and volumetric MRI changes in elderly patients with early-onset depression: a 2-year follow-up study.

Previous studies revealed personality changes in elderly patients with early-onset depression (EOD) that persist in euthymic stages. However, depression in older patients is a complex disorder that may affect not only personality, but also cognition and brain structure. To address this issue, a cross-sectional comparison and 2-year follow-up of 28 EOD elderly patients and 48 healthy controls included detailed neurocognitive assessment, estimates of brain volumes in limbic areas and white matter hyperintensities, as well as evaluation of the Five Factor Model of personality, in a remitted mood state. Results revealed that cognitive performances as well as brain volumes were preserved in EOD patients both at baseline and at follow-up. The increased Neuroticism factor and Anxiety facet scores as well as the decreased Warmth and Positive Emotions facet scores found at baseline reached the level of healthy controls after 2 years. Only the Depression facet scores remained significantly higher in EOD patients compared to controls upon follow-up. Results were independent of depressive relapse since baseline (25% of patients). These findings suggest that both cognitive performances and brain volumes show long-term preservation in older EOD patients. In contrast, the depression-related personality facet might be a trait like marker that persists in the long-term evolution of this disorder.

Neurocognitive deficits and personality traits among euthymic patients with mood disorders in late life.

BACKGROUND: Previous studies revealed that acute depressive episodes are associated with both cognitive deficits and modified personality patterns in late life. Whether or not these psychological changes are present after remission remains a matter of debate. To date, no study provided concomitant assessment of cognition and psychological functions in this particular clinical setting. METHOD: Using a cross-sectional design, 58 remitted outpatients (36 with unipolar early-onset depression (EOD) and 22 with bipolar disorder (BD)) were compared to 62 healthy controls. Assessment included detailed neurocognitive measures and evaluation of the five factor personality dimensions (NEO-Personality Inventory). RESULTS: Group comparisons revealed significant slower processing speed, working and episodic memory performances in BD patients. EOD patients showed cognitive abilities comparable to those of elderly controls. In NEO PI assessment, both BD and EOD patients displayed higher Depressiveness facet scores. In addition, the EOD but not BD group had lower Extraversion factor, and Warmth and Positive Emotion facet scores than controls. CONCLUSIONS: After remission from acute affective symptoms, older BD patients show significant impairment in several cognitive functions while neuropsychological performances remained intact in elderly patients with EOD. Supporting a long-lasting psychological vulnerability, EOD patients are more prone to develop emotion-related personality trait changes than BD patients.

Volumetric MRI changes, cognition and personality traits in old age depression.

BACKGROUND: The presence of cognitive and structural deficits in euthymic elderly depressed patients remains a matter of debate. Integrative aetiological models assessing concomitantly these parameters as well as markers of psychological vulnerability such as persistent personality traits, are still lacking for this age group. METHODS: Cross-sectional comparisons of 38 elderly remitted patients with early-onset depression (EOD) and 62 healthy controls included detailed neuropsychological assessment, estimates of brain volumes in limbic areas and white matter hyperintensities, as well as evaluation of the Five-Factor personality dimensions. RESULTS: Both cognitive performances and brain volumes were preserved in euthymic EOD patients. No significant group differences were observed in white matter hyperintensity scores between the two groups. In contrast, EOD was associated with significant increase of Neuroticism and decrease of Extraversion facet scores. LIMITATIONS: Results concern the restricted portion of EOD patients without psychiatric and physical comorbidities. Future longitudinal studies are necessary to determine the temporal relationship between the occurrence of depression and personality dimensions. CONCLUSIONS: After remission from acute depressive symptoms, cognitive performances remain intact in elderly patients with EOD. In contrast to previous observations, these patients display neither significant brain volume loss in limbic areas nor increased vascular burden compared to healthy controls. Further clinical investigations on EOD patterns of vulnerability in old age will gain from focusing on psychological features such as personality traits rather than neurocognitive clues.