A Neuropsychological Test Battery for Use in Alzheimer Disease Clinical Trials

Harrison, John; Minassian, Sonia L.; Jenkins, Lisa; Black, Ronald S.; Koller, Martin; Grundman, Michael

doi:10.1001/archneur.64.9.1323

Cited by 187 publications

(147 citation statements)

References 16 publications

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“…Some examples are the MMSE [44] which is the most frequently used test for AD diagnosis, the Severe Cognitive Impairment Scale [45], the Alzheimer's Disease Assessment ScaleCognitive [46] which focuses on attention, orientation, language, executive functioning and memory skills, the Neuropsychological Test Battery [47] which includes treatment effects' measurements, the Blessed Test which assesses memory, attention, concentration, and the ability to complete Activities of Daily Living (ADL) and the Severe Impairment Battery [48] which alternatively focuses on measuring the unaffected cognitive functions [49].…”

Section: Cognition Analysismentioning

confidence: 99%

On the early diagnosis of Alzheimer's Disease from multimodal signals: A survey

Alberdi

Aztiria

Basarab

2016

Artificial Intelligence in Medicine

162

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Section: Cognition Analysismentioning

confidence: 99%

On the early diagnosis of Alzheimer's Disease from multimodal signals: A survey

Alberdi

Aztiria

Basarab

2016

Artificial Intelligence in Medicine

162

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“…37 This could have been related to the fact that there was little decline in ADAS-cog-related cognitive functions in the placebo group. 37,40 In the same study, decreased CSF levels of tau protein, an intraneuronal microtubule-associated protein, were found, possibly as a correlate of slowed neuronal degeneration. 37 Histopathological examinations of autopsy tissues obtained from individual patients who died from unrelated causes revealed patchy patterns of ␤-amyloid plaque clearance in association with increased antibody titers, with some regions virtually free of ␤-amyloid plaque pathology.…”

Section: Initial Clinical Trialsmentioning

confidence: 75%

Targeting β-Amyloid Pathology in Alzheimer's Disease with Aβ Immunotherapy

Nitsch

Höck

2008

Neurotherapeutics

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Summary:More than 10 clinical trials of A␤ immunotherapy are currently underway in patients with Alzheimer's disease (AD). The aim is to identify safe approaches for the efficacious antibody-mediated removal of brain ␤-amyloid or its neurotoxic oligomeric precursors consisting of aggregated amyloid ␤-peptide (A␤). Initial experimental and neuro-pathological evidence for clearance of brain ␤-amyloid in response to A␤ immunotherapy is associated with structural and functional rescue of neurons, as well as initial signs of clinical stabilization and reduced rates of dementia progression. For the next steps in the future improvement of A␤ immunotherapy, major challenges in pharmacokinetics, safety, and tolerability need to be addressed. These include the low penetrations rates of IgG molecules through the blood-brain barrier, possible reductions in brain volume, the possibility of autoimmune disease related to unwanted crossreactivity with endogenous antigens on physiological structures, micro-hemorrhages related to cross-reaction with preexisting vascular amyloid pathology, possible relocalization of A␤ from ␤-amyloid plaques to brain blood vessels resulting in increased amyloid angiopathy, and the lacking activity of A␤ antibodies on pre-existing neurofibrillary tangle pathology, as well as the lacking molecular identification of the forms of A␤ to be therapeutically targeted. The solutions to these problems will be guided by the fine lines between tolerance and immunity against physiological and pathological structures, respectively, as well as by the understanding of the pathogenic transition of soluble A␤ into toxic oligomeric aggregation intermediates in the dynamic equilibrium of ␤-amyloid fibril assembly. Provided that the ongoing and planned clinical trials address these issues in a timely manner, there is a good chance for A␤ immunotherapy to be one of the first disease-modifying therapies of Alzheimer's disease to be introduced into clinical practice. Key Words: Humanized monoclonal antibody, neurodegeneration, vaccination, clinical trial, APP, passive immunization. PROOF OF CONCEPT IN EXPERIMENTAL ANIMALSThe concept of A␤ immunotherapy was first introduced by Schenk et al.1 who showed that vaccination with A␤1-42 and Freund's adjuvant prevented ␤-amyloid formation in brains of young transgenic mice and removed ␤-amyloid in older mice with pre-existing pathology. Subsequent active vaccinations in transgenic mice, nonhuman primates, and other species confirmed these findings 2-6 (For review, see references 7-10 ). Moreover, the passive transfer of antibodies against A␤ can efficiently reduce ␤-amyloid pathology.11-19 The immunotherapy-mediated clearance of ␤-amyloid pathology is paralleled by the recovery of neuronal and cytoskeletal morphology, 20,21 by the rescue of synaptic electrophysiological functions and neurotransmission, [22][23][24] and by signs of neuroprotection, 25 as well as by restored behavioral functions. 2,26 -28 While many antibodies show signs of efficacy in experimental animals, the...

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“…72,76 This may have been related to the relatively small decline in ADAScog (Alzheimer's Disease Assessment Scalecognitive subscale) scores in the placebo group. 72,77 Autopsy tissues from patients who died from unrelated causes showed patchy patterns of β-amyloid plaque clearance associated with increased antibody titers, with some regions almost totally free of β-amyloid plaques 70,71,78,79 In several cases, β-amyloid plaque reductions were associated with increased brain tissue concentrations of water and detergent-soluble forms of Aβ, 80 suggesting some biological plaque-clearing activity of antibodies occurred as a result of vaccination. No β-amyloid clearance was observed in a single case without detectable antibody titers.…”

Section: Development Of Anti-aβ Vaccination In Humansmentioning

confidence: 99%

The central role of T-cell memory in Alzheimer’s disease vaccination

Giunta¹,

Ruscin²,

Salemi³

et al. 2010

Ageing Res

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Alzheimer's disease (AD) is the most common progressive neurodegenerative brain disease as well as the most common dementia among the elderly. In the future as the average lifespan continues to extend, the number of AD patients will continue to grow. Amyloidbeta (Aβ) peptides, in both soluble oligomeric, and insoluble forms, are key in the neuropathogenesis of AD and have thus been a therapeutic target for vaccines. Multiple Aβ vaccination strategies in animal models of AD have demonstrated a marked reduction in both amyloid burden and neurocognitive deficits. Due to the success of these studies, initial human clinical trials of an active Aβ vaccine were conducted. These were discontinued due to the development of meningoencephalitis in approximately 6% of the vaccinated AD patients. Studies examining the brains of Aβ-vaccinated patients developing meningoencephalitis implicate Aβ-reactive T-cell subsets as major components of this deleterious response to active Aβ vaccination. To subvert possible meningoencephalitis resulting from Aβ vaccination a second generation of vaccines has been more recently developed. These however have met with little success in humans. To build on these findings, an understanding of the role of T-cells in vaccination against Aβ is presented in this review. Various methods of Aβ immunotherapy are reviewed including studies in both animal models and humans. Recent works suggest that Aβ-derived peptides delivered intranasally or transcutaneously results in effective clearance of Aβ plaques and improvement of cognitive function in animal models of AD. Moreover, undesired T-cell reactivity appeared to be considerably reduced compared with other active immunization strategies. In spite of the past clinical studies, these findings imply that Aβ vaccination may be both efficacious and safe depending route of delivery, adjuvant choice, and Aβ epitope administered.

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A Neuropsychological Test Battery for Use in Alzheimer Disease Clinical Trials

Cited by 187 publications

References 16 publications

On the early diagnosis of Alzheimer's Disease from multimodal signals: A survey

On the early diagnosis of Alzheimer's Disease from multimodal signals: A survey

Targeting β-Amyloid Pathology in Alzheimer's Disease with Aβ Immunotherapy

The central role of T-cell memory in Alzheimer’s disease vaccination

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