Benzodiazepines and antidepressants: Effects on cognitive and functional decline in Alzheimer's disease and Lewy body dementia

Objectives We aim to study the effects of the prescription of benzodiazepines and antidepressants on cognitive and functional decline in older adults living with Alzheimer's disease (AD) and Lewy body dementia (LBD) over a 5-year follow-up. Methods This is a longitudinal analysis of a Norwegian cohort study entitled “The Dementia Study of Western Norway” (DemVest). We included 196 patients newly diagnosed with AD (n = 111) and LBD (n = 85), followed annually for 5 years. Three prescription groups were defined: only benzodiazepines (BZD), only antidepressants (ADep), and the combination of benzodiazepines and antidepressants (BZD-ADep). Linear mixed-effects models were conducted to analyze the effect of the defined groups on the outcomes. The outcomes were functional decline, measured by the Rapid Disability Rating Scale—2, and cognition measured with the Mini-Mental State Examination. Results Prescription of the combination of benzodiazepines and antidepressants in LBD was associated with faster functional decline. In AD, the prescription of BZD and BZD-ADep was associated with greater functional deterioration. ADep alone did not show positive or negative significant associations with the studied outcomes. Conclusions BZD and especially the combination of BZD and ADep are associated with functional decline in AD and LBD and should be used cautiously.publishedVersio

Neuropsychiatric symptoms in dementia: long-term course and neuropathology

Aim: Neuropsychiatric symptoms (NPS) such as anxiety, apathy, and psychosis are important manifestations of dementia that have a major impact on the patient’s quality of life, carer burden, and risk of institutionalisation. There are few treatment options, the clinical course is not understood, and the mechanism behind the symptoms is unknown. This thesis analyses the frequency, long-term course, and pathological underpinnings of NPS. Methods: The Demvest study is a 12-year prospective longitudinal multicentre cohort study in the western part of Norway. Among the 667 patients with suspected mild dementia who were screened, 223 fulfilled the inclusion criteria were included and followed with annual assessments using the Neuropsychiatric Inventory (NPI). The attrition rate was very low, and data from 56 patients who underwent autopsy after death confirmed that the clinical diagnoses were highly accurate. The diagnostic distribution was 113 patients with Alzheimer’s disease (AD), 86 patients with Lewybody dementia (LBD), and 24 patients with other types of dementia. Results: NPS were common at baseline and only a moderate increase in NPS was observed during the first 5 years. There was also no increase in the proportion of patients with high NPI total scores. LBD was associated with a higher NPI total score and higher psychotic symptom scores. Most patients had a relapsing course or single symptomatic episodes rather than persistent symptoms, and 57% of AD and 84% of DLB patients had reoccurring psychotic symptoms. We found a significant association between cerebral amyloid angiopathy and psychosis in AD. Discussion: Severe NPS are already common at time of dementia diagnosis, and their increase with disease progression is moderate. We observed a highly individual course of NPS with unstable symptomatology. Cerebrovascular disease may increase the risk of psychosis in AD. The individual variations in NPS over time underline the need for personalised medicine in dementia care. NPS, including psychotic symptoms, should be highlighted as a natural part of the dementia syndrome

Differentiating traits and states identifies the importance of chronic neuropsychiatric symptoms for cognitive prognosis in mild dementia

Introduction Neuropsychiatric symptoms (NPS) in dementia are associated with poor cognitive outcomes in longitudinal studies. Whether this is due to differences in symptom burden between persons (BP) or changes within persons (WP) is unknown. Methods Patients with mild Alzheimer's disease (AD, n = 111) and Lewy-body dementia (LBD, n = 85) were assessed annually for 8 years. We modelled the association between NPS assessed by the Neuropsychiatric Inventory (NPI) and Mini-Mental State Examinations (MMSE) using Tobit mixed-effects model with NPS as individual means over time (BP) and its deviance (WP). Results The association between higher NPS and poorer cognitive outcomes was mostly due to BP differences for the NPI-total score, and in particular for delusions, hallucinations, agitation, aberrant motor behavior, and apathy scores. Discussion The NPS trait (BP) effect on cognitive decline is considerably stronger than the state effect (WP). Clinically, long-term rather than episodic NPS better identifies patients with poor cognitive outcomes

The individual course of neuropsychiatric symptoms in people with Alzheimer’s and Lewy body dementia: 12-year longitudinal cohort study

Introduction Understanding the natural course of neuropsychiatric symptoms (NPS) in dementia is important for planning patient care and trial design, but few studies have described the long-term course of NPS in individuals. Method Primary inclusion of 223 patients with suspected mild dementia from general practice were followed by annual assessment, including the Neuropsychiatric Inventory (NPI), for up to 12 years. Total and item NPI scores were classified as stable, relapsing, single episodic or not present based on 4.96 (s.d. 2.3) observations (98% completeness of longitudinal data) for 113 patients with Alzheimer's disease and 84 patients with LBD (68 dementia with Lewy bodies and 16 Parkinson's disease dementia). Results We found that 80% had stable NPI total ≥1, 50% had stable modest NPI total ≥12 and 25% had stable NPI total ≥24 scores. Very severe NPS (≥48) were mostly single episodes, but 8% of patients with Alzheimer's disease had stable severe NPS. Patients with Alzheimer's disease and the highest 20% NPI total scores had a more stable or relapsing course of four key symptoms: aberrant motor behaviour, aggression/agitation, delusions and irritability (odds ratio 55, P < 0.001). This was not seen in LBD. Finally, 57% of patients with Alzheimer's disease and 84% of patients with LBD had reoccurring psychotic symptoms. Conclusions We observed a highly individual course of NPS, with most presenting as a single episode or relapsing; a stable course was less common, especially in LBD. These findings demonstrate the importance of an individualised approach (i.e. personalised medicine) in dementia care.publishedVersio

Frailty in Older Adults with Mild Dementia: Dementia with Lewy Bodies and Alzheimer’s Disease

Introduction: The aim of the study is to describe the frequency of frailty in people with a new diagnosis of mild dementia due to Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB). Methods: This is a secondary analysis of the Dementia Study of Western Norway (Demvest). For this study, we analysed a sample of 186 patients, 116 with AD and 70 with DLB. Subjects were included at a time in which mild dementia was diagnosed according to consensus criteria after comprehensive standardized assessment. Frailty was evaluated retrospectively using a frailty index generated from existing data. The cut-off value used to classify an older adult as frail was 0.25. Results: The prevalence of frailty was 25.81% (n = 48). In the DLB group, 37.14% (n = 26) were classified as frail, compared to 18.97% (n = 22) of those with AD (p < 0.001). The adjusted multivariate analysis revealed an OR of 2.45 (1.15–5.23) for being frail in those with DLB when using AD as the reference group. Conclusion: Frailty was higher than expected in both types of dementia. The prevalence of frailty was higher in those with DLB compared to AD. This new finding underscores the need for a multi-systems approach in both dementias, with a particular focus on DLB

Advanced cerebral amyloid angiopathy and small vessel disease are associated with psychosis in Alzheimer's disease

This article is available to RD&E staff via NHS OpenAthens. Click on the Publisher URL, and log in with NHS OpenAthens if prompted.This study was funded by Norwegian Health Association. This paper represents independent research funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London.published version, accepted version, submitted versio

Frailty in Older Adults with Mild Dementia: Dementia with Lewy Bodies and Alzheimer’s Disease

Introduction: The aim of the study is to describe the frequency of frailty in people with a new diagnosis of mild dementia due to Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB). Methods: This is a secondary analysis of the Dementia Study of Western Norway (Demvest). For this study, we analysed a sample of 186 patients, 116 with AD and 70 with DLB. Subjects were included at a time in which mild dementia was diagnosed according to consensus criteria after comprehensive standardized assessment. Frailty was evaluated retrospectively using a frailty index generated from existing data. The cut-off value used to classify an older adult as frail was 0.25. Results: The prevalence of frailty was 25.81% (n = 48). In the DLB group, 37.14% (n = 26) were classified as frail, compared to 18.97% (n = 22) of those with AD (p < 0.001). The adjusted multivariate analysis revealed an OR of 2.45 (1.15–5.23) for being frail in those with DLB when using AD as the reference group. Conclusion: Frailty was higher than expected in both types of dementia. The prevalence of frailty was higher in those with DLB compared to AD. This new finding underscores the need for a multi-systems approach in both dementias, with a particular focus on DLB

Specific depressive symptoms are related with different patterns of alcohol use in community-dwelling older adults

Objectives To explore how individual depressive symptoms might contribute to different patterns of alcohol consumption in Colombian older adults living in the community. Methods A Secondary analysis from a nationally representative cross-sectional study of more than 23,000 older adults, with data from 19,004 participants. Drinking frequency, and level (moderate or heavy drinking) were used to assess alcohol use and depressive symptoms explored with the 15 items-GDS., using bivariate and multivariate adjusted regression models. Results Lower weekly drinking frequency and a higher number of drinks per serving were associated with total GDS score. For individual symptoms, higher drinking frequency was associated with dropping activities and a preference to stay at home. Lower drinking frequency was associated with low mood, unhappiness, feelings of emptiness, worthlessness, hopelessness, and a lack of vigour. Lower number of drinks per serving was associated with withdrawal/apathy related symptoms; these also related to higher frequency of weekly alcohol consumption. Higher number of drinks per serving was associated with feelings of emptiness, worthlessness, boredom, helplessness, worthlessness. not wanting to be alive, thinking that other people are better off in their mood, being afraid that something bad will happen and subjective memory problems. Moderate drinkers had a higher likelihood of reporting lack of vigour. Conclusion There were diverse patterns of alcohol use according to individual depressive symptoms. This has implications for interventions to reduce alcohol related harm in older people across a range of depressive symptoms with different patterns of alcohol use