A. Von Gunten

Brain aging in the oldest-old.

Nonagenarians and centenarians represent a quickly growing age group worldwide. In parallel, the prevalence of dementia increases substantially, but how to define dementia in this oldest-old age segment remains unclear. Although the idea that the risk of Alzheimers disease (AD) decreases after age 90 has now been questioned, the oldest-old still represent a population relatively resistant to degenerative brain processes. Brain aging is characterised by the formation of neurofibrillary tangles (NFTs) and senile plaques (SPs) as well as neuronal and synaptic loss in both cognitively intact individuals and patients with AD. In nondemented cases NFTs are usually restricted to the hippocampal formation, whereas the progressive involvement of the association areas in the temporal neocortex parallels the development of overt clinical signs of dementia. In contrast, there is little correlation between the quantitative distribution of SP and AD severity. The pattern of lesion distribution and neuronal loss changes in extreme aging relative to the younger-old. In contrast to younger cases where dementia is mainly related to severe NFT formation within adjacent components of the medial and inferior aspects of the temporal cortex, oldest-old individuals display a preferential involvement of the anterior part of the CA1 field of the hippocampus whereas the inferior temporal and frontal association areas are relatively spared. This pattern suggests that both the extent of NFT development in the hippocampus as well as a displacement of subregional NFT distribution within the Cornu ammonis (CA) fields may be key determinants of dementia in the very old. Cortical association areas are relatively preserved. The progression of NFT formation across increasing cognitive impairment was significantly slower in nonagenarians and centenarians compared to younger cases in the CA1 field and entorhinal cortex. The total amount of amyloid and the neuronal loss in these regions were also significantly lower than those reported in younger AD cases. Overall, there is evidence that pathological substrates of cognitive deterioration in the oldest-old are different from those observed in the younger-old. Microvascular parameters such as mean capillary diameters may be key factors to consider for the prediction of cognitive decline in the oldest-old. Neuropathological particularities of the oldest-old may be related to “longevity-enabling” genes although little or nothing is known in this promising field of future research.

Stereological analysis of neuropil threads in the hippocampal formation: relationships with Alzheimer's disease neuronal pathology and cognition

Although neuropil threads are thought to account for 85–90% of cortical tau pathology in brain ageing, their clinical significance remains controversial. Previous studies have measured densities, rather than absolute numbers, and most did not take into account possible interactions among the pathological hallmarks of Alzheimers disease (AD). We report here stereological estimates of total neurofibrillary tangle (NFT) and neuron numbers as well as total amyloid volume and neuropil thread (NT) length, in the hippocampus and entorhinal cortex of 19 very old individuals (age range: 83–101 years) with various degrees of cognitive decline. Total NT length in all areas studied increased in mildly demented cases but showed a marked decrease in Clinical Dementia Rating (CDR) scale 3 cases. Both total NFT and neuron numbers were related to NT length in the CA1 field and entorhinal cortex. A strong positive relationship was also present between the total NFT numbers in the entorhinal cortex and NT length in the CA1 field and dentate gyrus. Total NT length in the CA1 field was related to both CDR scores and presence or absence of dementia explaining 7% and 37% of their variability respectively. In multivariate models, this relationship was highly dependent on the severity of NFT formation in this area. Our data reveal that NT formation in hippocampal subdivisions and entorhinal cortex accompanies AD neuronal pathology in early stages of the degenerative process, yet its rate may decrease in severe dementia. In terms of clinicopathological correlations, NT length in the hippocampal formation does not represent an independent marker of dementia severity.

Personality Traits and Behavioural and Psychological Symptoms in Patients with Mild Cognitive Impairment

Background and Aims: Both personality changes and behavioural and psychological symptoms (BPS) may be associated with mild cognitive impairment (MCI) in later life and help identify incipient dementia. We wished to investigate the links between personality and BPS in MCI. Method: We studied premorbid personality traits as estimated 5 years back and their changes in 83 control subjects and 52 MCI patients using the revised NEO Personality Inventory for the Five-Factor Model completed by a proxy. Information on BPS was obtained using the Neuropsychiatric Inventory (NPI). Analyses were controlled for current depression and anxiety. Results: Premorbid neuroticism and openness to experience were associated with the total NPI score. The changes in neuroticism, extraversion, openness to experiences, and conscientiousness were associated with apathy and affective symptoms. Conclusions: Personality changes and BPS occur in MCI. The occurrence of affective BPS and apathy is associated with both premorbid personality traits and their changes.

The Evolution of Personality in Patients with Mild Cognitive Impairment

Aims: To describe personality traits and their changes in mild cognitive impairment (MCI) and control subjects. Methods: Sixty-three MCI and 90 control subjects were asked to describe their current personality traits by the Structured Interview for the Five-Factor Model (SIFFM). For each subject, a close relative retrospectively assessed these descriptions both as to the previous and current personality traits, using the Revised NEO Personality Inventory, Form R (NEO-PI-R). Results: Self-assessed MCI subjects reported significantly lower scores in the openness dimension than control subjects [F(1, 150) = 9.84, p = 0.002, ηp2 = 0.06]. In current observer ratings, MCI subjects had higher scores on neuroticism [F(1, 137) = 7.55, p = 0.007, ηp2 = 0.05] and lower ones on extraversion [F(1, 137) = 6.40, p = 0.013, ηp2 = 0.04], openness [F(1, 137) = 9.93, p = 0.002, ηp2 = 0.07], agreeableness [F(1, 137) = 10.18, p = 0.002, ηp2 = 0.07] and conscientiousness [F(1, 137) = 25.96, p < 0.001, ηp2 = 0.16]. Previous personality traits discriminated the groups as previous openness [odds ratio (OR) = 0.97, 95% confidence interval (CI) = 0.95-0.99, p = 0.014] and conscientiousness (OR = 0.96, 95% CI 0.94-0.98, p = 0.001) were negatively related to MCI group membership. In MCI subjects, conscientiousness [F(1, 137) = 19.20, p < 0.001, ηp2 = 0.12] and extraversion [F(1, 137) = 22.27, p < 0.001, ηp2 = 0.14] decreased between previous and current evaluations and neuroticism increased [F(1, 137) = 22.23, p < 0.001, ηp2 = 0.14], whereas no significant change was found in control subjects. Conclusions: MCI subjects undergo significant personality changes. Thus, personality assessment may aid the early detection of dementia.

Resident health-related quality of life in Swiss nursing homes.

BACKGROUND Health-related quality of life (HRQOL) levels and their determinants in those living in nursing homes are unclear. The aim of this study was to investigate different HRQOL domains as a function of the degree of cognitive impairment and to explore associations between them and possible determinants of HRQOL. METHOD Five HRQOL domains using the Minimum Data Set - Health Status Index (MDS-HSI) were investigated in a large sample of nursing home residents depending on cognitive performance levels derived from the Cognitive Performance Scale. Large effect size associations between clinical variables and the different HRQOL domains were looked for. RESULTS HRQOL domains are impaired to variable degrees but with similar profiles depending on the cognitive performance level. Basic activities of daily living are a major factor associated with some but not all HRQOL domains and vary little with the degree of cognitive impairment. LIMITATIONS This study is limited by the general difficulties related to measuring HRQOL in patients with cognitive impairment and the reduced number of variables considered among those potentially influencing HRQOL. CONCLUSION HRQOL dimensions are not all linearly associated with increasing cognitive impairment in NH patients. Longitudinal studies are required to determine how the different HRQOL domains evolve over time in NH residents.

DI-073 Off label use of psychotropic drugs in elderly patients with dementia in a psychogeriatric unit

Background The use of antidementia drugs indicated for the treatment of certain cognitive, behavioural and psychological symptoms related to dementia (BPSD) in elderly patients is limited because of their low efficacy. Therefore, other psychotropic drugs are commonly prescribed off-label. Data on off-label prescriptions of psychotropic drugs for BPSD are scarce. Purpose To assess both the frequency of psychotropic prescriptions for the treatment of BPSD and the conformity of prescriptions to official Swissmedic monographs1 (OSM) and to Swiss recommendations 20142 (SR). Material and methods Retrospective and descriptive study of patients discharged between June 1st 2013 and January 31st 2014 from the Organic Psychiatric Disorders Unit of the Geriatric Psychiatry Service of a primary and tertiary care university hospital. The number and the type of drugs prescribed were investigated and the percentage of conformity to references was analysed. Results 835 different drugs were prescribed to the 94 patients included. The average number of drugs per patient was 9 ± 3, including 4 ± 2 psychotropic drugs. Dementia was diagnosed in 89 of them for whom 409 psychotropic prescriptions were identified. Of these 409 prescriptions, 395 prescriptions targeted the treatment of BPSD. The conformity with OSM and SR were respectively 59.0% and 68.9% according to indication, 54.2% and 64.6% according to the route of administration, 38.0% and 38.8% according to the initial dose, 43.2% and 30.8% according to the maximum dose, 35.4% and 52.2% according to the duration of treatment. Conclusion Patients treated in a primary and tertiary hospital due to BPSD are systematically prescribed psychotropic medication, often outside the official recommendations. This may emphasise the substantial and unmet needs of approved drugs to treat BPSD. References Swissmedic. http://www.swissmedicinfo.ch/ (last access July 06, 2014) Savaskan, E. et al. Empfehlungen zur Diagnostik und Therapie der behavioralen und psychologischen Symptome der Demenz (BPSD). PRAXIS 2014;103:135–48 No conflict of interest.

EPA-1390 – CRTC3 polymorphisms are not associated with obesity in swiss psychiatric populations

Introduction Weight gain and obesity are serious problems associated with psychiatric diseases, in which psychotropic treatments play an important role. The CREB-regulated transcription coactivator 3 ( CRTC3 ) gene was linked to energy balance in animal models, and in humans CRTC3 rs8033595 polymorphism was associated with obesity markers only in Mexican-Americans, a population with a high prevalence of obesity. Objectives To determine whether polymorphisms within the CRTC3 gene are associated with adiposity markers in Caucasian psychiatric patients, a population with also a high prevalence of obesity. Method The association of the CRTC3 rs8033595 and 2 other selected CRTC3 polymorphisms (rs3743401 and rs3902286) was investigated in three independent groups of Caucasian psychiatric patients taking weight gain-inducing psychotropic drugs such as atypical antipsychotics, lithium and valproate (n 1 =168, n 2 =188, and n 3 =448). Body mass index (BMI) was chosen as a marker for obesity. Generalized Additive Mixed Model (GAMM) was used to test the association of CRTC3 polymorphisms with BMI. Results Obesity prevalence was high in the three psychiatric populations (n 1 :40%, n 2 :28% and n 3 :19%). The three CRTC3 polymorphisms did not deviate from Hardy-Weinberg equilibrium and the minor allelic frequency (MAF) was 44%, 25% and 19% for CRTC3 rs8033595, rs3743401 and rs3902286 , respectively. None of the CRTC3 polymorphisms were found to be associated with BMI in any of the three psychiatric samples and when analyzing the combined samples together. Conclusion CRTC3 polymorphisms seem not to have an influence on adiposity markers (BMI) in Caucasian psychiatric patients receiving drugs inducing weight gain.

EPA-1389 – Predictive values of appetite and early weight increase for long-term weight variation during psychotropic treatment.

Introduction Atypical antipsychotics and some other psychotropic drugs such as valproate, lithium or mirtazapine are known to induce several metabolic complications. However there is an inter-individual variability in developing metabolic features which may be explained by clinical and genetic factors. Objectives To determine whether weight gain and/or appetite change after one month are predictors for a weight gain after 3 and 12 months of treatment. Methods A longitudinal clinical and pharmacogenetic study is presently ongoing in the Department of Psychiatry-CHUV. Several clinical data have been recorded over one year following the introduction of psychotropic treatment. 406 patients with weight at baseline, after one month and with at least a third weight measure during the first year of treatment were included in the present study. Results Using Receiver Operating Characteristic (ROC) analyses, an initial weight increase of 5% was found to be a good predictor for a consequent weight gain at 3 months (ROC AUC =77) and one year (ROC AUC =68). By using a generalized linear mixed model corrected by several confounders, this weight change of 5% was found to be significantly associated (p-value Conclusion An initial weight gain of 5% during the first month following an introduction of atypical antipsychotics, lithium, valproate and/or mirtazapine is a predictor for further weight gain and should be a warning sign to introduce weight lowering strategies.

CP-076 Effects of pharmacist interventions on inappropriate prescribing in a geriatric psychiatry unit

Background A prospective observational study was conducted in 2012 in order to evaluate prescription of potentially inappropriate medicines (PIM) in a geriatric psychiatry unit (GPU) of Lausanne University Hospital.1 The STOPP/START criteria, an explicit screening tool, were used to detect PIM.2 This study showed a high number of PIM. Therefore, introducing a clinical pharmacist in this unit was suggested as a strategy to improve the quality of prescribing by reducing PIM. Purpose To assess the impact of a clinical pharmacist on PIM by measuring the acceptance rate of the pharmacist’s interventions (PI) in a GPU. Materials and methods A clinical pharmacy service was implemented in this GPU (16 beds) in order to optimise drug prescription. A clinical pharmacist was integrated in the multidisciplinary team and attended a variety of weekly meetings (pharmacotherapy discussions, new inpatient presentation meeting, nursing staff reports). She performed a daily medicines review (history, conciliation, checking for interaction, consultation of the electronic medical notes, laboratory data, detecting PIM with STOPP/START criteria). These activities could lead to PI with physicians if drug-related problems were observed. These PI could come from the STOPP/START criteria or after a standard pharmacist appraisal. They were categorised using the Swiss Association of Public Health Administration & Hospital Pharmacists classification [3] and communicated to physicians during meetings, in private discussions or by email. The impact of this activity was measured by the acceptance rate of the PI (number of PI accepted/total number of PI). Results Data collection started at the end of July 2013. In the last interim analysis dated 11 October, 33 patients were included. 172 PI had been made (117 standard PI and 55 STOPP/START PI) which represents 5.2 PI per patient. Acceptance rate was 85% for standard PI and 47% for STOPP/START PI. Conclusions This interim analysis shows a good integration of the clinical pharmacist into the healthcare staff with a satisfactory level of acceptance rate. However, a difference in acceptance between standard and STOPP/START PI was observed and needs to be confirmed by further inclusions. This difference may be related to the limitation of this explicit tool in geriatric psychiatry. References Weibel M-L, et al. http://www.chuv.ch/pha/pha_home/pha-recherche/pha-recherche-contributions/pha-recherche-contributions-travauxdiplomes.htm Gallager, et al. Int J Clin Pharmacol Ther 2008;46(2):72-83 http://www.gsasa.ch/pages/activites/activites-cliniques/?oid=1587&lang=FR No conflict of interest.