Christoph Mueller

The prognosis of dementia with Lewy bodies

Dementia with Lewy bodies is the second most common form of neurodegenerative dementia, yet scarce evidence is available about its prognosis and natural history, which are crucial to inform clinical practice and research. Patients with dementia with Lewy bodies might have a less favourable prognosis, with accelerated cognitive decline, shorter lifespan, and increased admission to residential care than patients with Alzheimers disease. Health-care costs and, importantly, caregiver burden, are also reported to be higher in dementia with Lewy bodies than in Alzheimers disease. It is probable that causative factors for this less favourable prognosis are the increased prevalence and early emergence of neuropsychiatric symptoms in patients with dementia with Lewy bodies, and the challenge of accurate diagnosis. Evidence concerning quality of life and hospital admission rates is limited, despite their clinical and economic relevance.

Associations of acetylcholinesterase inhibitor treatment with reduced mortality in Alzheimer's disease: a retrospective survival analysis

Background dementia is increasingly recognised as life-limiting condition. Although the benefits of acetylcholinesterase inhibitors (AChEIs) on cognition and function are well established, their effect on survival is less clear. Objective to investigate associations between AChEI prescription and mortality in patients with Alzheimers dementia (AD) in a naturalistic setting, using detailed baseline data on cognition, functioning, and mental and physical wellbeing. Methods we used a large mental healthcare database in South London, linked to Hospital Episode Statistics and Office for National Statistics mortality data, to assemble a retrospective cohort. We conducted a survival analysis adjusting for a wide range of potential confounders using propensity scores to reduce the impact of confounding by indication. Results of 2,464 patients with AD, 1,261 were prescribed AChEIs. We detected a strong association between AChEI receipt and lower mortality (hazard ratio = 0.57; 95% CI 0.51-0.64). This remained significant after controlling for a broad range of potential confounders including psychotropic co-prescription, symptom severity, functional status and hospital admissions (hazard ratio = 0.77; 95% CI 0.67-0.87). Conclusions in a large cohort of patients with AD, AChEI prescription was associated with reduced risk of death by more than 20% in adjusted models. This has implications for individual care planning and service development.

Polypharmacy in people with dementia: Associations with adverse health outcomes

&NA; Polypharmacy has been linked to higher risks of hospitalisation and death in community samples. It is commonly present in people with dementia but these risks have rarely been studied in this population. We aimed to investigate associations between polypharmacy and emergency department attendance, any and unplanned hospitalisation, and mortality in patients with dementia. Using a large mental health care database in South London, linked to hospitalisation and mortality data, we assembled a retrospective cohort of patients diagnosed with dementia. We ascertained number of medications prescribed at the time of dementia diagnosis and conducted multivariate Cox regression analyses. Of 4668 patients with dementia identified, 1128 (24.2%) were prescribed 4–6 medications and 739 (15.8%) ≥7 medications. Compared to those using 0–3 medications, patients with dementia using 4–6 or ≥7 agents had an increased risk of emergency department attendance (hazard ratio 1.20/1.35), hospitalisation (hazard ratio 1.12/1.32), unplanned hospital admission (hazard ratio 1.12/1.25), and death within two years (hazard ratio 1.29/1.39) after controlling for potential confounders. We found evidence of a dose response relationship with each additional drug at baseline increasing the risk of emergency department attendance and mortality by 5% and hospitalisation by 3%. In conclusion, polypharmacy at dementia diagnosis is associated with a higher risk of adverse health outcomes. Future research is required to elucidate which specific agents underlie this relationship and if reduction of inappropriate prescribing is effective in preventing these outcomes in dementia.

Predictors of falls and fractures leading to hospitalization in people with schizophrenia spectrum disorder: A large representative cohort study

AIM To investigate predictors of falls/fractures leading to hospitalisation in people with schizophrenia-spectrum disorders. METHODS A historical cohort of people with schizophrenia-spectrum disorders (ICD F20-29) from 01/2006-12/2012 was assembled using data from the South London and Maudsley NHS Biomedical Research Centre Case Register. Falls/fractures were ascertained from a linkage to national hospitalisation data. Separate multivariate Cox regression analyses were employed to identify predictors of falls and fractures. RESULTS Of 11,567 people with schizophrenia-spectrum disorders (mean age 42.6 years, 43% female), 579 (incidence rate 12.79 per 1000 person-years) and 528 (11.65 per 1000 person-years) had at least one reported hospital admission due to a fall or fracture respectively and 822 patients had at least either a recorded fall or a fracture during this period (i.e. 7.1% of sample). Overall, 6.69 and 10.74 years of inpatient hospital stay per 1000-person years of follow-up occurred due to a fall and fracture respectively. 14(0.12%) and 28(0.24%) died due to a fall and fracture respectively. In Multivariable analysis, increasing age, white ethnicity, analgesics, cardiovascular disease, hypertension, diseases of the genitourinary system, visual disturbance and syncope were significant risk factor for both falls and fractures. A previous fracture (HR 2.05, 95% CI 1.53-2.73) and osteoporosis (HR 6.79, 95% CI 4.71-9.78) were strong risk factors for consequent fractures. CONCLUSION Comorbid physical health conditions and analgesic medication prescription were associated with higher risk of falls and fractures. Osteoporosis and previous fracture were strong predictors for subsequent fractures. Interventions targeting bone health and falls/fractures need to be developed and evaluated in these populations.

Cardiovascular Outcomes of Cholinesterase Inhibitors in Individuals with Dementia: A Meta‐Analysis and Systematic Review

To evaluate the cardiovascular (CV) effects of acetylcholinesterase inhibitors (AChEIs) in individuals with dementia

Corrigendum: Aspirin and incident depressive symptoms: A longitudinal cohort study over 8 years

REFERENCE 1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Washington DC: American Psychiatric Press; 2013. 2. Fichman‐Charchat H, Miranda CV, Fernandes CS, et al. Brief Cognitive Screening Battery (BCSB) is a very useful tool for diagnosis of probable mild Alzheimers disease in a geriatric clinic. Arq Neuro‐Psiquiat. 2016; 74:149‐154. 3. Üstün TB, Chatterji S, Kostanjsek N, et al. Developing the world health organization disability assessment schedule 2.0. Bull World Health Organ 2010;88:815–823. 4. Han JW, So Y, Kim TH, et al. Prevalence rates of dementia and mild cognitive impairment are affected by the diagnostic parameter changes for neurocognitive disorders in the DSM‐5 in a Korean population. Dement Geriatr Cogn. 2017;43:193‐203. 5. Eramudugolla R, Mortby ME, Sachdev P, Meslin C, Kumar R, Anstey KJ. Evaluation of a research diagnostic algorithm for DSM‐5 neurocognitive disorders in a population‐based cohort of older adults. Alzheimers Res Ther. 2017;9:15. TABLE 1 Clinical and sociodemoghraphic characteristics of the sample (N = 209)

Investigating the relationship between age of onset of depressive disorder and cognitive function

Depressive disorder is commonly associated with impaired cognitive function; however, it is unclear whether the age of onset of the first episode of depression, current depression severity, or historical severity of depressive episodes are associated with cognitive performance.

Assessment and Management of Neuropsychiatric Symptoms in Parkinson’s Disease

Neuropsychiatric symptoms are highly prevalent in Parkinson’s disease and associated with decreased quality of life and adverse health outcomes. In this review, the assessment and management of common neuropsychiatric symptoms are discussed: depression, anxiety, psychosis, cognitive impairment, dementia and apathy. Validated assessment scales are now available for the majority of symptoms. Balancing dopaminergic therapy plays an important role in their management as increasing doses of dopaminergic agents might address depression and anxiety related to ‘off’ phases, non-motor fluctuations and apathy, while dose reduction might alleviate psychotic symptoms. More targeted treatment is possible through medications utilising different pathways. Although efficacy profiles of individual agents require further exploration, antidepressants as a drug class have shown utility in depression and anxiety in Parkinson’s disease. Psychological therapies, especially cognitive behavioural approaches, are effective. Pimavanserin allows the treatment of psychosis in Parkinson’s disease without directly affecting the dopaminergic and cholinergic system. The cholinergic system is currently the only target in Parkinson’s disease dementia, and antagonists of this system, as are many psychotropic drugs, need to be used with caution. Management of apathy largely relies on non-pharmacological strategies adapted from dementia care, with antidepressants being ineffective and the role of stimulant therapy needing further evaluation.

'Attending to the wound and the person - patients' experiences and expectations of a newly established traumatic brain injury clinic.

ABSTRACT Primary objective: This qualitative study aimed to gain a better understanding of how medical and social services in the UK currently support patients with Traumatic Brain Injury (TBI) in the community. Furthermore, we explored patients’ wishes and expectations of a newly established TBI clinic. Methods and procedures: We conducted semi-structured interviews with 10 patients with mild-to-severe TBI. The interview schedule was designed to cover contacts with health services, information provided, post-discharge support, current social circumstances, expectations from the newly established brain injury service and participants’ desires for any new service. Transcripts were analysed using a thematic analysis. Main results: Participants highlighted the importance of the human component of their care and of fostering trusting relationships. This validates patients’ experience and helps them to regain confidence. Follow-up and education are important for patients and relatives through all stages of care, regardless of the severity of the injury. Patients strive for meaningful lives and need to be supported to engage in activities. They need hands-on support, particularly with the UK’s bureaucratic welfare system. Conclusions: There is much room for improvement in the TBI community care in the UK. Our findings support the development of a holistic service that can address the multifactorial problems which the patients with TBI and their families face.

CONCOMITANT USE OF ANTICHOLINERGIC MEDICATION ATTENUATES BENEFITS OF CHOLINESTERASE INHIBITORS IN ALZHEIMER’S DISEASE: A LARGE COHORT STUDY OF SURVIVAL AND COGNITIVE FUNCTION

Figure. Comparison of longitudinal change in MMSE Babak Hooshmand, Helga Refsum, A. David Smith, Ingemar K areholt, Christine von Arnim, Erika Jonsson Laukka, Lars B€ackman, Laura Fratiglioni, Miia Kivipelto, Karolinska Institutet, Stockholm, Sweden; Ulm University Hospital, Ulm, Germany; Oslo University, Oslo, Norway; Oxford University, Oxford, United Kingdom; Karolinska Institute, Stockholm, Sweden; Stockholm Gerontology Research Center, Stockholm, Sweden; Kuopio University Hospital, Kuopio, Finland; National Institute for Health and Welfare, Helsinki, Finland; Karolinska Institutet-Stockholm University, Stockholm, Sweden; University of Eastern Finland, Kuopio, Finland. Contact e-mail: Babak.Hooshmand@ki.se