Serotonin augmentation therapy by escitalopram has minimal effects on amyloid-β levels in early-stage Alzheimer’s-like disease in mice

Abstract Background Dysfunction of the serotonergic (5-HTergic) system has been implicated in the cognitive and behavioural symptoms of Alzheimer’s disease (AD). Accumulation of toxic amyloid-β (Aβ) species is a hallmark of AD and an instigator of pathology. Serotonin (5-HT) augmentation therapy by treatment with selective serotonin reuptake inhibitors (SSRIs) in patients with AD has had mixed success in improving cognitive function, whereas SSRI administration to mice with AD-like disease has been shown to reduce Aβ pathology. The objective of this study was to investigate whether an increase in extracellular levels of 5-HT induced by chronic SSRI treatment reduces Aβ pathology and whether 5-HTergic deafferentation of the cerebral cortex could worsen Aβ pathology in the APPswe/PS1ΔE9 (APP/PS1) mouse model of AD. Methods We administered a therapeutic dose of the SSRI escitalopram (5 mg/kg/day) in the drinking water of 3-month-old APP/PS1 mice to increase levels of 5-HT, and we performed intracerebroventricular injections of the neurotoxin 5,7-dihydroxytryptamine (DHT) to remove 5-HTergic afferents. We validated the effectiveness of these interventions by serotonin transporter autoradiography (neocortex 79.7 ± 7.6%) and by high-performance liquid chromatography for 5-HT (neocortex 64% reduction). After 6 months of escitalopram treatment or housing after DHT-induced lesion, we evaluated brain tissue by mesoscale multiplex analysis and sections by IHC analysis. Results Amyloid-β-containing plaques had formed in the neocortex and hippocampus of 9-month-old APP/PS1 mice after 6 months of escitalopram treatment and 5-HTergic deafferentation. Unexpectedly, levels of insoluble Aβ42 were unaffected in the neocortex and hippocampus after both types of interventions. Levels of insoluble Aβ40 increased in the neocortex of SSRI-treated mice compared with those treated with vehicle control, but they were unaffected in the hippocampus. 5-HTergic deafferentation was without effect on the levels of insoluble/soluble Aβ42 and Aβ40 in both the neocortex and hippocampus. However, levels of soluble amyloid precursor protein α were reduced in the neocortex after 5-HTergic deafferentation. Conclusions Because this study shows that modulation of the 5-HTergic system has either no effect or increases levels of insoluble/soluble Aβ42 and Aβ40 in the cerebral cortex of APP/PS1 mice, our observations do not support 5-HT augmentation therapy as a preventive strategy for reducing Aβ pathology

Weight increase in patients with dementia, and alteration in meal routines and meal environment after integrity promoting care

AIMS: To follow weight changes in patients with moderate and severe dementia and analyse how these changes related to biological and psychological parameters after staff education and support in integrity promoting care. A further aim was to describe meal environment and routines relative to the intervention. BACKGROUND: Weight loss in patients with dementia and in particular Alzheimer’s disease (AD) is common. The etiology appears multifactorial with the meal environment and a decreased independence while eating among the factors. METHOD: Over a three-month intervention period, an integrity-promoting care training program was conducted with the staff of a long-term ward. AD patients, 18 from an intervention ward and 15 from a control ward were included and possible effects were evaluated. Weighing was conducted at the start and after completion of the intervention. Weight changes were analyzed in relation to psychological and biochemical parameters. In addition, the staff wrote diaries about e.g. changes made in the environment and in their work.RESULTS: The most prominent difference observed was weight increases in 13 of 18 patients compared to two of 15 patients in the control ward. No weight changes were related to the type of dementia. The individual weight changes correlated significant to changes in the intellectual functions. Relationships between weight change, increased motor function and increased appetite were non-significant. There was no significant relationship between weight changes and changes in biochemical parameters. According to the staff, increased contact with the patients and a more pleasant atmosphere resulted when the meal environment and routines were changed. RELEVANCE TO CLINICAL PRACTICE: Weight gain in patients with moderate and severe dementia was achieved by adjusting the meal environment to the individual’s needs. Staff education was profitable, as increased competence seemed to promote individually adapted feeding situations. Ensuring good meal situations need to be given high priority.</p

Inappropriate long-term use of antipsychotic drugs is common among people with dementia living in specialized care units

BACKGROUND: Antipsychotic drugs are widely used for the treatment of Behavioral and Psychological Symptoms of Dementia (BPSD), despite their limited efficacy and concerns about safety. The aim of this study was to describe antipsychotic drug therapy among people with dementia living in specialized care units in northern Sweden. METHODS: This study was conducted in 40 specialized care units in northern Sweden, with a total study population of 344 people with dementia. The study population was described in regard to antipsychotic drug use, ADL function, cognitive function and BPSD, using the Multi-Dimensional Dementia Assessment Scale (MDDAS). These data were collected at baseline and six months later. Detailed data about antipsychotic prescribing were collected from prescription records. RESULTS: This study showed that 132 persons (38%) in the study population used antipsychotic drugs at the start of the study. Of these, 52/132 (39%) had prescriptions that followed national guidelines with regard to dose and substance.After six months, there were 111 of 132 persons left because of deaths and dropouts. Of these 111 people, 80 (72%) were still being treated with antipsychotics, 63/111 (57%) with the same dose. People who exhibited aggressive behavior (OR: 1.980, CI: 1.515-2.588), or passiveness (OR: 1.548, CI: 1.150-2.083), or had mild cognitive impairment (OR: 2.284 CI: 1.046-4.988), were at increased risk of being prescribed antipsychotics. CONCLUSION: The prevalence of antipsychotic drug use among people with dementia living in specialized care units was high and inappropriate long-term use of antipsychotic drugs was common