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7 results

  • 32 - Disappointing Results of Two Human Trials of Monoclonal Antibodies in Parkinson’s Disease

  • Daniel Gibbs, Emeritus of Oregon Health and Science University
  • Book:
    Dispatches from the Land of Alzheimer's
    Published online:
    19 January 2024
    Print publication:
    22 February 2024, pp 130-133

  • Summary

    Like Alzheimer’s disease, Parkinson’s disease is a progressive, neurodegenerative disorder that involves deposits of an abnormal protein in the brain. In Alzheimer’s disease, these abnormal proteins are extracellular beta-amyloid and intraneuronal, hyperphosphorylated tau. In Parkinson’s disease, the neuropathological findings are protein deposits of aggregated alpha-synuclein found primarily within neurons in a part of the brainstem called the substantia nigra but in other locations as well. These clumps of alpha-synuclein are called Lewy bodies.

    In the August 4, 2022 issue of the New England Journal of Medicine, we have reports of two phase 2 human trials of monoclonal antibodies directed at alpha-synuclein in subjects with early-stage Parkinson’s disease, prasinezumab and cinpanemab.

  • Ecological validity of cognitive fluctuations in dementia with Lewy bodies

  • Troy A. Webber, Sara A. Lorkiewicz, Andrew M. Kiselica, Steven P. Woods
  • Journal:
    Journal of the International Neuropsychological Society / Volume 30 / Issue 1 / January 2024
    Published online by Cambridge University Press:
    14 April 2023, pp. 35-46
    • Article
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  • Objectives:

    Cognitive fluctuations are a core clinical feature of dementia with Lewy bodies (DLB), but their contribution to the everyday functioning difficulties evident DLB are not well understood. The current study evaluated whether intraindividual variability across a battery of neurocognitive tests (intraindividual variability-dispersion) and daily cognitive fluctuations as measured by informant report are associated with worse daily functioning in DLB.

    Methods:

    The study sample included 97 participants with consensus-defined DLB from the National Alzheimer’s Coordinating Center (NACC). Intraindividual variability-dispersion was measured using the coefficient of variation, which divides the standard deviation of an individual’s performance scores across 12 normed neurocognitive indices from the NACC neuropsychological battery by that individual’s performance mean. Informants reported on daily cognitive fluctuations using the Mayo Fluctuations Scale (MFS) and on daily functioning using the functional activities questionnaire (FAQ).

    Results:

    Logistic regression identified a large univariate association of intraindividual variability-dispersion and presence of daily cognitive fluctuations on the MFS (Odds Ratio = 73.27, 95% Confidence Interval = 1.38, 3,895.05). Multiple linear regression demonstrated that higher intraindividual variability-dispersion and presence of daily cognitive fluctuations as assessed by the MFS were significantly and independently related to worse daily functioning (FAQ scores).

    Conclusions:

    Among those with DLB, informant-rated daily cognitive fluctuations and cognitive fluctuations measured in the clinic (as indexed by intraindividual variability-dispersion across a battery of tests) were independently associated with poorer everyday functioning. These data demonstrate ecological validity in measures of cognitive fluctuations in DLB.

  • Antipsychotic Prescribing Practices in Those with Parkinsonism: Adherence to Guidelines

  • Heather B. Rigby, Sara Rehan, Barbara Hill-Taylor, Kara Matheson, Ingrid Sketris
  • Journal:
    Canadian Journal of Neurological Sciences / Volume 44 / Issue 5 / September 2017
    Published online by Cambridge University Press:
    08 May 2017, pp. 603-606
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  • Several evidence-informed treatment guidelines recommend against the use of typical antipsychotics in patients with Parkinson’s disease; of the atypical antipsychotics, clozapine and quetiapine are preferred. The purpose of this study is to determine the frequency with which potentially inappropriate antipsychotics are dispensed to older adults in Nova Scotia who are on levodopa-containing medications. In this cohort, 59.9% were dispensed a preferred atypical antipsychotic and 12.6% a potentially harmful typical antipsychotic. Our results suggest that potentially inappropriate prescribing practices are common in the neuropsychiatric management of patients with parkinsonism and that there is an opportunity for education and improvement in prescribing practices.

  • Chapter 8 - Prion diseases

  • Nicholas Wood
  • Book:
    Neurogenetics
    Published online:
    05 May 2012
    Print publication:
    12 April 2012, pp 103-120

  • Summary

    Alzheimer's disease is the major cause of dementia in the elderly and afflicts about four million Americans. This chapter focuses on AD and discusses other dementias to the extent to which they contribute to our understanding of AD. While AD is easily the most prevalent dementing disease, other rarer dementias offer useful comparators. These include dementia with Lewy bodies (DLB), prion disease, Worster drought syndrome (British dementia), and frontal temporal dementia (FTD) with tangles (FTDP-17T). The genetic findings have enabled the creation of transgenic mice that model parts of the disease process. While Alzheimer patients are undoubtedly better treated than they were 15 years ago, the only direct benefit to patients from this gene-based approach to research, to date, has been the availability of genetic testing in the kindreds with amyloid beta precursor protein gene (APP) and presenilin mutations.

  • Case 27 - Frontotemporal lobar dementia vs. solvent intoxication: A piece that does not fit the puzzle

  • Edited by Serge Gauthier, McGill University, Montréal, Pedro Rosa-Neto, McGill University, Montréal
  • Book:
    Case Studies in Dementia
    Published online:
    16 May 2011
    Print publication:
    21 April 2011, pp 201-207

  • Summary

    This chapter talks about a 75-year-old retired sailor who was in very good overall physical condition. At the first assessment, the sailor reported a gradual cognitive decline, subjectively described as memory impairment, during the last 2 years. The neurologist diagnosed mild right-sided Parkinsonism in upper body, with tremor and bradykinesia, but no rigor. Walking was near normal, but he was unsteady on turning and had a pathological pull-test. This case presented with asymmetric Parkinsonism, and cognitive impairment was noted at the time of diagnosis. Thus, the important differential diagnoses were possible: dementia associated with Lewy Bodies (DLB) or Dementia associated with Parkinson's disease (PDD). DLB is characterized by dementia accompanied by idiopathic Parkinsonism, cognitive fluctuation, and persistent visual hallucinations. PDD and DLB have similar clinical presentation as well as underlying brain changes, and differentiation between the two syndromes is entirely based on the relative timing of Parkinsonism and cognitive impairment.

  • 26 - Neuroimaging of Parkinson's disease

  • from Section IV - Cognitive Disorders
  • Edited by Martha E. Shenton, Bruce I. Turetsky, University of Pennsylvania
  • Book:
    Understanding Neuropsychiatric Disorders
    Published online:
    10 January 2011
    Print publication:
    09 December 2010, pp 361-370

  • Summary

    This chapter discusses the recent neuroimaging studies that have started to unravel some of the mysteries behind the behavior and cognitive manifestations of Parkinson's disease (PD). In-vivo anatomical and functional confirmation of the cortico-striatal loops in humans comes from magnetic resonance imaging (MRI) techniques. In the early stages of PD, frontal lobe dysfunction most likely reflects deafferentation in relation to dopamine deficiency. In keeping with neuropathological studies, which have demonstrated Lewy bodies and cell loss in medial temporal lobe areas high-resolution MRI images have demonstrated hippocampal atrophy in PD. There is pathological and in-vivo positron emission tomography (PET) evidence that other neurotransmitters, particularly cholinergic pathways, are involved in PD dementia (PDD). In-vivo PET studies are currently investigating whether concomitant amyloid pathology may contribute to dementia in PD subjects, although at this point, it appears that amyloid deposition is associated more with dementia with Lewy bodies (DLB) than with PDD.