Michaela Poppe - Academia.edu (original) (raw)

Papers by Michaela Poppe

Lancet, Jan 30, 2011

Depression is common in dementia but the evidence base for appropriate drug treatment is sparse a... more Depression is common in dementia but the evidence base for appropriate drug treatment is sparse and equivocal. We aimed to assess efficacy and safety of two of the most commonly prescribed drugs, sertraline and mirtazapine, compared with placebo.

J Neurol Neurosurg Psychiat, 2006

Prescribed drugs in patients with Alzheimer's disease may affect the symptomatic progress... more Prescribed drugs in patients with Alzheimer's disease may affect the symptomatic progression of their disease, both positively and negatively. To examine the effects of drugs on the progression of disease in a representative group of patients with Alzheimer's disease. Patients with the diagnosis of probable Alzheimer's disease were recruited from the community. The prescribed drugs taken by 224 patients (mean age 82.3 years) were recorded at initial assessment and then correlated in logistic regression analysis with progression of the disease, defined as an increase of one point or more in the Global Deterioration Scale over the next 12-month period. Patients who were taking antipsychotic drugs and sedatives had a significantly higher risk of deterioration than those who were taking none (odds ratios (ORs) 2.74 (95% confidence interval (CI) 1.17 to 6.41) and 2.77 (95% CI 1.14 to 6.73), respectively). Higher risk of deterioration was observed in those who were taking both antipsychotic and sedative drugs together (OR 3.86 (95% CI 1.28 to 11.7). Patients taking drugs licensed for dementia, drugs affecting the renin-angiotensin system and statins had a significantly lower risk of deterioration than those who were not taking any of these drugs (ORs 0.49 (95% CI 0.25 to 0.97), 0.31 (95% CI 0.11 to 0.85) and 0.12 (95% CI 0.03 to 0.52), respectively). Our findings have implications for both clinicians and trialists. Most importantly, clinicians should carefully weigh any potential benefits of antipsychotics and benzodiazepines, especially in combination, against the risk of increased decline. Researchers need to be aware of the potential of not only licensed drugs for dementia but also drugs affecting the renin-angiotensin system and statins in reducing progression in clinical trials.

Health technology assessment (Winchester, England), 2013

Depression is common in dementia, causing considerable distress and other negative impacts. Treat... more Depression is common in dementia, causing considerable distress and other negative impacts. Treating it is a clinical priority, but the evidence base is sparse and equivocal. This trial aimed to determine clinical effectiveness of sertraline and mirtazapine in reducing depression 13 weeks post randomisation compared with placebo. Multicentre, parallel-group, double-blind placebo-controlled randomised controlled trial of the clinical effectiveness of sertraline and mirtazapine with 13- and 39-week follow-up. Nine English old-age psychiatry services. A pragmatic trial. Eligibility: probable or possible Alzheimer's disease (AD), depression (4+ weeks) and Cornell Scale for Depression in Dementia (CSDD) score of 8+. clinically too critical (e.g. suicide risk); contraindication to medication; taking antidepressants; in another trial; and having no carer. (1) Sertraline; (2) mirtazapine; and (3) placebo, all with normal care. Target doses: 150 mg of sertraline or 45 mg of mirtazapine d...

Neurobiology of Aging, 2004

PLoS ONE, 2013

End-of-life-care is often poor in individuals with dementia. Advanced care planning (ACP) has the... more End-of-life-care is often poor in individuals with dementia. Advanced care planning (ACP) has the potential to improve end-of-life care in dementia. Commonly ACP is completed in the last six months of life but in dementia there may be problems with this as decision-making capacity and ability to communicate necessarily decrease as the disease progresses. Choosing the right time to discuss ACP with people with dementia may be challenging given the duration of the illness may be up to nine years. To explore the acceptability of discussing ACP with people with memory problems and mild dementia shortly after diagnosis. In-depth interviews were conducted with 12 patients and eight carers who had participated in ACP discussions and six staff members from a memory clinic and a community mental health team who had either conducted or attended the discussions for training purposes. Patients and carers found ACP a positive intervention that helped them think about the future, enabled people with dementia to make their wishes known, and resulted in their feeling relieved and less worried about the future. The importance of sharing the ACP documentation between health service providers was highlighted. This qualitative evaluation of ACP in early dementia has encouragingly positive results which support the wider application of the intervention in memory services and community mental health teams. Strategies are suggested to support the implementation of ACP further in clinical practice.

Neuroscience Letters, 2004

Alzheimer's disease (AD) is a disorder without a molecular marker in peripheral tissues or a dise... more Alzheimer's disease (AD) is a disorder without a molecular marker in peripheral tissues or a disease modifying treatment. As increasing evidence has suggested a role for glycogen synthase kinase-3 (GSK-3) in the pathogenesis of the condition we measured total GSK-3 protein (alpha and beta isoforms) and GSK-3 activity (serine 9 phosphorylation) in a group of healthy elderly people, in AD and in mild cognitive impairment (MCI). Total GSK-3 protein was increased in both AD and in MCI without a compensatory decrease in activity. These data suggest that GSK-3 assays might be a useful diagnostic marker in a readily available tissue and moreover that GSK-3 activity is increased in the prodromal phase of the disorder suggesting that inhibition of GSK-3 might be a useful therapeutic strategy.

NeuroImage, 2011

It is poorly understood why people with Down syndrome (DS) are at extremely high-risk of developi... more It is poorly understood why people with Down syndrome (DS) are at extremely high-risk of developing Alzheimer's disease (AD) compared to the general population. One explanation may be related to their extra copy of risk factors modulated by chromosome 21. Myo-inositol (mI), whose transporter gene is located on chromosome 21, has been associated with dementia in the non DS population; however, nobody has contrasted brain mI in DS with (DS+) and without (DS-) dementia to other non-DS groups. Our primary aim was to compare the hippocampal concentration of mI ([mI]) and other brain metabolites such as N-acetylaspartate (NAA; a proxy measure of neuronal density and mitochondrial function) in DS+, DS-, and age-matched healthy controls using proton Magnetic Resonance Spectroscopy ( 1 H-MRS). We compared hippocampal [mI] and other metabolites in 35 individuals with genetically-confirmed DS [DS+ (n=17,age=53+6) and DS-(n=18,age=47+8)] to age-matched healthy controls (n=13,age=51+10) adjusting for proportion of the MRS voxel occupied by cerebrospinal spinal fluid, and grey/white matter. DS+ had a significantly higher [mI] than both DS-and healthy controls. In contrast neither DS+ nor DS-differed significantly from controls in [NAA] (although NAA in DS+ was significantly lower than DS-). Our secondary aim of comparing brain metabolites in DS+ and DS-to Alzheimer's disease (AD; n=39;age=77+5) revealed that the DS+ group had significantly elevated [mI] compared to AD or DS-. [mI] may modify risk for dementia in this vulnerable population.

Neurobiology of Aging, 2004

Journal of Neurology, Neurosurgery & Psychiatry, 2006

Examining the role of metacognition in psychological distress in Parkinson's disease View project... more Examining the role of metacognition in psychological distress in Parkinson's disease View project The effect of a lab-based, single exposure of attention training technique on self-focused attention Background: Prescribed drugs in patients with Alzheimer's disease may affect the symptomatic progression of their disease, both positively and negatively. Aim: To examine the effects of drugs on the progression of disease in a representative group of patients with Alzheimer's disease. Methods: Patients with the diagnosis of probable Alzheimer's disease were recruited from the community. The prescribed drugs taken by 224 patients (mean age 82.3 years) were recorded at initial assessment and then correlated in logistic regression analysis with progression of the disease, defined as an increase of one point or more in the Global Deterioration Scale over the next 12-month period. Results: Patients who were taking antipsychotic drugs and sedatives had a significantly higher risk of deterioration than those who were taking none (odds ratios (ORs) 2.74 (95% confidence interval (CI) 1.17 to 6.41) and 2.77 (95% CI 1.14 to 6.73), respectively). Higher risk of deterioration was observed in those who were taking both antipsychotic and sedative drugs together (OR 3.86 (95% CI 1.28 to 11.7). Patients taking drugs licensed for dementia, drugs affecting the renin-angiotensin system and statins had a significantly lower risk of deterioration than those who were not taking any of these drugs (ORs 0.49 (95% CI 0.25 to 0.97), 0.31 (95% CI 0.11 to 0.85) and 0.12 (95% CI 0.03 to 0.52), respectively). Conclusion: Our findings have implications for both clinicians and trialists. Most importantly, clinicians should carefully weigh any potential benefits of antipsychotics and benzodiazepines, especially in combination, against the risk of increased decline. Researchers need to be aware of the potential of not only licensed drugs for dementia but also drugs affecting the renin-angiotensin system and statins in reducing progression in clinical trials.

Investigative Radiology, 1989

International Journal of Geriatric Psychiatry, 2009

Objective: To determine the effects of early life education, mid life employment and later life r... more Objective: To determine the effects of early life education, mid life employment and later life retirement age on the age of onset (AOO) of Alzheimer's disease (AD). Methods: Multiple regression analyses were carried out using data for 1320 probable AD cases, of which 382 were males with employment and retirement age data, using informant based information on education and employment. Results: No relation was found between years of education, best qualification obtained, or employment variables in males and the AOO of AD. A significant effect of later retirement age in delaying the AOO of AD was seen in males. Conclusions: In this study no effect of education or employment was seen, although this may be due to limited variance in the study population. The significant effect of retirement age may have several explanations, the most interesting of which would be the suggestion that active employment later in life allows an individual to prolong their cognitive assets above the threshold for dementia.

International Journal of Geriatric Psychiatry, 2008

Objective To assess the safety and feasibility of prescribing long term lithium to elderly people... more Objective To assess the safety and feasibility of prescribing long term lithium to elderly people with mild to moderate Alzheimer's disease (AD). Methods An open label treatment group with low dose lithium for up to 1 year with the Lithium Side Effects Rating Scale as the primary outcome measure. A comparison group matched for cognition and age not receiving lithium therapy. Results Twenty-two people with AD initiated lithium. Fourteen participants discontinued therapy after a mean of 16 weeks of treatment compared to the 39 weeks for those continuing to take treatment at the end of the study. Three patients discontinued treatment due to possible side effects that abated on ceasing therapy. The reports of side effects on the primary outcome scale did not differ between those discontinuing therapy and those remaining in the study. Two patients died whilst receiving lithium--in neither case was the treatment felt to be related to cause of death. There was no difference in deaths, drop outs or change in MMSE between those receiving lithium and the comparison group. Conclusions Lithium treatment in elderly people with AD has relatively few side effects and those that were apparently due to treatment were mild and reversible. Nonetheless discontinuation rates are high. The use of lithium as a potential disease modification therapy in AD should be explored further but is not without problems.

Lancet, Jan 30, 2011

Depression is common in dementia but the evidence base for appropriate drug treatment is sparse a... more Depression is common in dementia but the evidence base for appropriate drug treatment is sparse and equivocal. We aimed to assess efficacy and safety of two of the most commonly prescribed drugs, sertraline and mirtazapine, compared with placebo.

The British Journal of Psychiatry, 2010

Alzheimer's & Dementia, 2006

Alzheimer's & Dementia, 2006

delay recall (MCIϭ1.3Ϯ1.8, Cϭ4.1Ϯ2.6; Uϭ1044, pϽ0.001). Conclusions: This study showed that beyon... more delay recall (MCIϭ1.3Ϯ1.8, Cϭ4.1Ϯ2.6; Uϭ1044, pϽ0.001). Conclusions: This study showed that beyond consolidation deficits, MCI patients have difficulties in acquisition and recall strategies. This knowledge is relevant for the understanding of the pathophysiology of MCI, and helps to delineate future rehabilitation interventions in these patients.

Alzheimer's & Dementia, 2006

Lancet, Jan 30, 2011

Depression is common in dementia but the evidence base for appropriate drug treatment is sparse a... more Depression is common in dementia but the evidence base for appropriate drug treatment is sparse and equivocal. We aimed to assess efficacy and safety of two of the most commonly prescribed drugs, sertraline and mirtazapine, compared with placebo.

J Neurol Neurosurg Psychiat, 2006

Prescribed drugs in patients with Alzheimer's disease may affect the symptomatic progress... more Prescribed drugs in patients with Alzheimer's disease may affect the symptomatic progression of their disease, both positively and negatively. To examine the effects of drugs on the progression of disease in a representative group of patients with Alzheimer's disease. Patients with the diagnosis of probable Alzheimer's disease were recruited from the community. The prescribed drugs taken by 224 patients (mean age 82.3 years) were recorded at initial assessment and then correlated in logistic regression analysis with progression of the disease, defined as an increase of one point or more in the Global Deterioration Scale over the next 12-month period. Patients who were taking antipsychotic drugs and sedatives had a significantly higher risk of deterioration than those who were taking none (odds ratios (ORs) 2.74 (95% confidence interval (CI) 1.17 to 6.41) and 2.77 (95% CI 1.14 to 6.73), respectively). Higher risk of deterioration was observed in those who were taking both antipsychotic and sedative drugs together (OR 3.86 (95% CI 1.28 to 11.7). Patients taking drugs licensed for dementia, drugs affecting the renin-angiotensin system and statins had a significantly lower risk of deterioration than those who were not taking any of these drugs (ORs 0.49 (95% CI 0.25 to 0.97), 0.31 (95% CI 0.11 to 0.85) and 0.12 (95% CI 0.03 to 0.52), respectively). Our findings have implications for both clinicians and trialists. Most importantly, clinicians should carefully weigh any potential benefits of antipsychotics and benzodiazepines, especially in combination, against the risk of increased decline. Researchers need to be aware of the potential of not only licensed drugs for dementia but also drugs affecting the renin-angiotensin system and statins in reducing progression in clinical trials.

Health technology assessment (Winchester, England), 2013

Depression is common in dementia, causing considerable distress and other negative impacts. Treat... more Depression is common in dementia, causing considerable distress and other negative impacts. Treating it is a clinical priority, but the evidence base is sparse and equivocal. This trial aimed to determine clinical effectiveness of sertraline and mirtazapine in reducing depression 13 weeks post randomisation compared with placebo. Multicentre, parallel-group, double-blind placebo-controlled randomised controlled trial of the clinical effectiveness of sertraline and mirtazapine with 13- and 39-week follow-up. Nine English old-age psychiatry services. A pragmatic trial. Eligibility: probable or possible Alzheimer's disease (AD), depression (4+ weeks) and Cornell Scale for Depression in Dementia (CSDD) score of 8+. clinically too critical (e.g. suicide risk); contraindication to medication; taking antidepressants; in another trial; and having no carer. (1) Sertraline; (2) mirtazapine; and (3) placebo, all with normal care. Target doses: 150 mg of sertraline or 45 mg of mirtazapine d...

Neurobiology of Aging, 2004

PLoS ONE, 2013

End-of-life-care is often poor in individuals with dementia. Advanced care planning (ACP) has the... more End-of-life-care is often poor in individuals with dementia. Advanced care planning (ACP) has the potential to improve end-of-life care in dementia. Commonly ACP is completed in the last six months of life but in dementia there may be problems with this as decision-making capacity and ability to communicate necessarily decrease as the disease progresses. Choosing the right time to discuss ACP with people with dementia may be challenging given the duration of the illness may be up to nine years. To explore the acceptability of discussing ACP with people with memory problems and mild dementia shortly after diagnosis. In-depth interviews were conducted with 12 patients and eight carers who had participated in ACP discussions and six staff members from a memory clinic and a community mental health team who had either conducted or attended the discussions for training purposes. Patients and carers found ACP a positive intervention that helped them think about the future, enabled people with dementia to make their wishes known, and resulted in their feeling relieved and less worried about the future. The importance of sharing the ACP documentation between health service providers was highlighted. This qualitative evaluation of ACP in early dementia has encouragingly positive results which support the wider application of the intervention in memory services and community mental health teams. Strategies are suggested to support the implementation of ACP further in clinical practice.

Neuroscience Letters, 2004

Alzheimer's disease (AD) is a disorder without a molecular marker in peripheral tissues or a dise... more Alzheimer's disease (AD) is a disorder without a molecular marker in peripheral tissues or a disease modifying treatment. As increasing evidence has suggested a role for glycogen synthase kinase-3 (GSK-3) in the pathogenesis of the condition we measured total GSK-3 protein (alpha and beta isoforms) and GSK-3 activity (serine 9 phosphorylation) in a group of healthy elderly people, in AD and in mild cognitive impairment (MCI). Total GSK-3 protein was increased in both AD and in MCI without a compensatory decrease in activity. These data suggest that GSK-3 assays might be a useful diagnostic marker in a readily available tissue and moreover that GSK-3 activity is increased in the prodromal phase of the disorder suggesting that inhibition of GSK-3 might be a useful therapeutic strategy.

NeuroImage, 2011

It is poorly understood why people with Down syndrome (DS) are at extremely high-risk of developi... more It is poorly understood why people with Down syndrome (DS) are at extremely high-risk of developing Alzheimer's disease (AD) compared to the general population. One explanation may be related to their extra copy of risk factors modulated by chromosome 21. Myo-inositol (mI), whose transporter gene is located on chromosome 21, has been associated with dementia in the non DS population; however, nobody has contrasted brain mI in DS with (DS+) and without (DS-) dementia to other non-DS groups. Our primary aim was to compare the hippocampal concentration of mI ([mI]) and other brain metabolites such as N-acetylaspartate (NAA; a proxy measure of neuronal density and mitochondrial function) in DS+, DS-, and age-matched healthy controls using proton Magnetic Resonance Spectroscopy ( 1 H-MRS). We compared hippocampal [mI] and other metabolites in 35 individuals with genetically-confirmed DS [DS+ (n=17,age=53+6) and DS-(n=18,age=47+8)] to age-matched healthy controls (n=13,age=51+10) adjusting for proportion of the MRS voxel occupied by cerebrospinal spinal fluid, and grey/white matter. DS+ had a significantly higher [mI] than both DS-and healthy controls. In contrast neither DS+ nor DS-differed significantly from controls in [NAA] (although NAA in DS+ was significantly lower than DS-). Our secondary aim of comparing brain metabolites in DS+ and DS-to Alzheimer's disease (AD; n=39;age=77+5) revealed that the DS+ group had significantly elevated [mI] compared to AD or DS-. [mI] may modify risk for dementia in this vulnerable population.

Neurobiology of Aging, 2004

Journal of Neurology, Neurosurgery & Psychiatry, 2006

Examining the role of metacognition in psychological distress in Parkinson's disease View project... more Examining the role of metacognition in psychological distress in Parkinson's disease View project The effect of a lab-based, single exposure of attention training technique on self-focused attention Background: Prescribed drugs in patients with Alzheimer's disease may affect the symptomatic progression of their disease, both positively and negatively. Aim: To examine the effects of drugs on the progression of disease in a representative group of patients with Alzheimer's disease. Methods: Patients with the diagnosis of probable Alzheimer's disease were recruited from the community. The prescribed drugs taken by 224 patients (mean age 82.3 years) were recorded at initial assessment and then correlated in logistic regression analysis with progression of the disease, defined as an increase of one point or more in the Global Deterioration Scale over the next 12-month period. Results: Patients who were taking antipsychotic drugs and sedatives had a significantly higher risk of deterioration than those who were taking none (odds ratios (ORs) 2.74 (95% confidence interval (CI) 1.17 to 6.41) and 2.77 (95% CI 1.14 to 6.73), respectively). Higher risk of deterioration was observed in those who were taking both antipsychotic and sedative drugs together (OR 3.86 (95% CI 1.28 to 11.7). Patients taking drugs licensed for dementia, drugs affecting the renin-angiotensin system and statins had a significantly lower risk of deterioration than those who were not taking any of these drugs (ORs 0.49 (95% CI 0.25 to 0.97), 0.31 (95% CI 0.11 to 0.85) and 0.12 (95% CI 0.03 to 0.52), respectively). Conclusion: Our findings have implications for both clinicians and trialists. Most importantly, clinicians should carefully weigh any potential benefits of antipsychotics and benzodiazepines, especially in combination, against the risk of increased decline. Researchers need to be aware of the potential of not only licensed drugs for dementia but also drugs affecting the renin-angiotensin system and statins in reducing progression in clinical trials.

Investigative Radiology, 1989

International Journal of Geriatric Psychiatry, 2009

Objective: To determine the effects of early life education, mid life employment and later life r... more Objective: To determine the effects of early life education, mid life employment and later life retirement age on the age of onset (AOO) of Alzheimer's disease (AD). Methods: Multiple regression analyses were carried out using data for 1320 probable AD cases, of which 382 were males with employment and retirement age data, using informant based information on education and employment. Results: No relation was found between years of education, best qualification obtained, or employment variables in males and the AOO of AD. A significant effect of later retirement age in delaying the AOO of AD was seen in males. Conclusions: In this study no effect of education or employment was seen, although this may be due to limited variance in the study population. The significant effect of retirement age may have several explanations, the most interesting of which would be the suggestion that active employment later in life allows an individual to prolong their cognitive assets above the threshold for dementia.

International Journal of Geriatric Psychiatry, 2008

Objective To assess the safety and feasibility of prescribing long term lithium to elderly people... more Objective To assess the safety and feasibility of prescribing long term lithium to elderly people with mild to moderate Alzheimer's disease (AD). Methods An open label treatment group with low dose lithium for up to 1 year with the Lithium Side Effects Rating Scale as the primary outcome measure. A comparison group matched for cognition and age not receiving lithium therapy. Results Twenty-two people with AD initiated lithium. Fourteen participants discontinued therapy after a mean of 16 weeks of treatment compared to the 39 weeks for those continuing to take treatment at the end of the study. Three patients discontinued treatment due to possible side effects that abated on ceasing therapy. The reports of side effects on the primary outcome scale did not differ between those discontinuing therapy and those remaining in the study. Two patients died whilst receiving lithium--in neither case was the treatment felt to be related to cause of death. There was no difference in deaths, drop outs or change in MMSE between those receiving lithium and the comparison group. Conclusions Lithium treatment in elderly people with AD has relatively few side effects and those that were apparently due to treatment were mild and reversible. Nonetheless discontinuation rates are high. The use of lithium as a potential disease modification therapy in AD should be explored further but is not without problems.

Lancet, Jan 30, 2011

Depression is common in dementia but the evidence base for appropriate drug treatment is sparse a... more Depression is common in dementia but the evidence base for appropriate drug treatment is sparse and equivocal. We aimed to assess efficacy and safety of two of the most commonly prescribed drugs, sertraline and mirtazapine, compared with placebo.

The British Journal of Psychiatry, 2010

Alzheimer's & Dementia, 2006

Alzheimer's & Dementia, 2006

delay recall (MCIϭ1.3Ϯ1.8, Cϭ4.1Ϯ2.6; Uϭ1044, pϽ0.001). Conclusions: This study showed that beyon... more delay recall (MCIϭ1.3Ϯ1.8, Cϭ4.1Ϯ2.6; Uϭ1044, pϽ0.001). Conclusions: This study showed that beyond consolidation deficits, MCI patients have difficulties in acquisition and recall strategies. This knowledge is relevant for the understanding of the pathophysiology of MCI, and helps to delineate future rehabilitation interventions in these patients.

Alzheimer's & Dementia, 2006