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6 results

  • 35 - Pharmacogenetics in Alzheimer’s Disease Drug Discovery and Personalized Treatment

  • from Section 4 - Imaging and Biomarker Development in Alzheimer’s Disease Drug Discovery
  • Edited by Jeffrey Cummings, University of Nevada, Las Vegas, Jefferson Kinney, University of Nevada, Las Vegas, Howard Fillit
  • Book:
    Alzheimer's Disease Drug Development
    Published online:
    03 March 2022
    Print publication:
    31 March 2022, pp 404-417

  • Summary

    Alzheimer’s disease (AD) is a priority health problem devoid of curative treatment. The medication currently available includes acetylcholinesterase inhibitors (AChEIs)(donepezil, rivastigmine, galantamine, huperzine) and memantine. Only one new drug has been approved by the FDA in the last 17 years, so a shift in the paradigm of finding new treatments seems imperative. This involves a better understanding of AD pathogenesis, identifying predictive biomarkers, and customizing treatments. The implementation of pharmacogenomic procedures is an efficient option to optimize the scarce resources available and to accelerate the discovery of new treatments. The pharmacogenomic machinery is composed of pathogenic, mechanistic, metabolic, transporter and pleiotropic genes, under strict regulatory control of epigenetic mechanisms. Since dementia patients suffer from other concomitant diseases and receive up to 10 or more different medications, pharmacogenetics predicts therapeutic response, reduce drug interactions, and limit the adverse effects of anti-dementia drugs.

  • Cardiac monitoring in memory clinics: national survey of UK practice

  • George Crowther, Noura Ahmed, Deepa Kasa, Zoe Goff, Muzahir H. Tayebjee
  • Journal:
    BJPsych Bulletin / Volume 47 / Issue 1 / February 2023
    Published online by Cambridge University Press:
    26 November 2021, pp. 11-16
    Print publication:
    February 2023
    • Article
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      • Open access
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  • Aims and method

    People diagnosed with dementia are often started on acetylcholinesterase inhibitors (AChEIs). As AChEIs can be associated with cardiac side-effects, an electrocardiogram (ECG) is sometimes requested before treatment. Previous work has suggested there is little consensus as to when or how ECGs should be obtained. This can create inconsistent practice, with patient safety, economic and practical repercussions. We surveyed 305 UK memory clinic practitioners about prescribing practice.

    Results

    More than 84% of respondents completed a pulse and cardiac history before prescribing AChEIs. Opinion was divided as to who should fund and conduct ECGs. It was believed that obtaining an ECG causes patients inconvenience and delays treatment. Despite regularly interpreting ECGs, 76% of respondents did not update this clinical skill regularly.

    Clinical implications

    The variation in practice observed has service-level and patient implications and raises potential patient safety concerns. Implementing national guidelines or seeking novel ways of conducting cardiac monitoring could help standardise practice.

  • The challenges of diagnosis and treatment of dementia in Down’s syndrome

  • R. M. Vaughan, C. McGee, S. Guerin, J. Tyrrell, P. Dodd
  • Journal:
    Irish Journal of Psychological Medicine / Volume 33 / Issue 3 / September 2016
    Published online by Cambridge University Press:
    03 February 2016, pp. 151-158
    Print publication:
    September 2016
  • Objectives

    People with Down syndrome (DS) are at high risk for developing dementia and early diagnosis is vital in enhancing quality of life. Our aim was to compare our practice to consensus recommendations on evaluation, diagnosis and pharmacological treatment of individuals with DS who develop dementia. We also aimed to establish the average time taken to make a diagnosis of dementia and to commence pharmacotherapy, and to assess tolerability to acetylcholinesterase inhibitors.

    Methods

    Retrospective chart review in an exhaustive sample containing all current service users attending our service with DS and a diagnosis of dementia (n=20).

    Results

    The sample was 75% female and 70% had a moderate intellectual disability. The average age at diagnosis of dementia was 52.42 years old. The average time to diagnosis from first symptom was 1.13 years and the average time to commence pharmacotherapy was 0.23 years. A total of 17 patients commenced on acetylcholinesterase inhibitors, and of these seven discontinued medication due to side-effects or lack of efficacy.

    Conclusions

    The results on anticholinesterases add to the limited pool of data on treatment of dementia in DS. There was an identified need to improve the rates of medical, vision and hearing assessments, and prospective screening. Deficiencies in screening and diagnosis may be addressed by implementing a standardised dementia assessment pathway to include prospective screening and longitudinal assessment using easily administered scales. We highlight the importance of improving the diagnostic process, as a vital window of opportunity to commence a comprehensive care plan may be lost.

  • Patterns of psychotropic medication use in nursing homes: surveys in Sydney, allowing comparisons over time and between countries

  • John Snowdon, Daniel Galanos, Divya Vaswani
  • Journal:
    International Psychogeriatrics / Volume 23 / Issue 9 / November 2011
    Published online by Cambridge University Press:
    24 March 2011, pp. 1520-1525

  • Background: This study aimed to explore changes in patterns of use of psychotropic medication in Sydney nursing homes over recent years, and to compare current usage rates with those reported from other countries.

    Methods: Data were obtained from 44 of the 48 nursing homes in a central Sydney health area. Researchers noted details from medication cards concerning residents’ age, gender and all currently prescribed drugs, checking whether medication had been given as prescribed. Frequency of administration of “as required” drugs in the previous four weeks was noted.

    Results: The pattern of use of psychotropic medication changed considerably between 1993 and 2009. The number of residents taking regularly administered antipsychotics increased by 24% during 1998–2009, though mean dosages decreased. In 2009, fewer residents took hypnotic and/or anxiolytic medications than in the 1990s, and fewer than in countries from which equivalent data have been reported. Antidepressant use increased over the 16 years but only to 25.6%. Only 3% of residents in Sydney nursing homes in 2009 took cognition-enhancing drugs.

    Conclusions: Compared to other countries, rates of use of hypnotic, anxiolytic and antidepressant medication in Sydney nursing homes are low. Benefits and disadvantages of these differences merit analysis. Antipsychotic medications were administered to similar percentages of survey residents in 1993 and 2009, but at lower mean dosages in 2009 compared to previous surveys, and with a change to using mainly atypical antipsychotic drugs. Compared to various other countries, cognition-enhancing and antidepressant medications are administered to proportionally fewer residents in Sydney nursing homes. Outcome analysis regarding the use and benefits of such drugs in nursing homes is desirable.

  • Correlates of Dropout, Efficacy, and Adverse Events in Treatment With Acetylcholinesterase Inhibitors in Korean Patients With Alzheimer's Disease

  • Jae-Min Kim, Il-Seon Shin, Jin-Sang Yoon
  • Journal:
    International Psychogeriatrics / Volume 14 / Issue 2 / June 2002
    Published online by Cambridge University Press:
    10 January 2005, pp. 187-195

  • The correlates of dropout, efficacy, and adverse events in the tratment of Alzheimer's disease (AD) with acetylcholinesterase inhibitors (ChEI) are unclear. To investigate these issues, a 26-week prospective, randomized, open-labeled trail with donepezil or rivastigmine was undertaken. Sixty-four Korean patients with AD were recruited, and data on sociodemographic and clinical characteristics and several assessment scales were collected. Characteristics of available caregivers were also gathered. Information on adverse events and dropout was recorded. Thirty-five (55%) patients dropped out during treatment with ChEI, for reasons mainly related to financial burden of caregivers. Of the 29 patients who completed the 26-week trial, 16 (55%) were responsive to ChEI. Lower scores on the Clinical Dementia Rating and Blessed Dementia Scale at baseline were associated with the efficacy of ChEI. Of the total participants, 26 (41%) experienced adverse events, although these seemed to be mild and appeared to be associated with the psychological state of patients or coadministration of psychotropic drugs. In conclusion, ChEI seemed to be effective and well tolerated in the treatment of Korean patients with AD, but the use of this drug was limited mainly by the financial burden of caregivers.