Regional brain activity after prolonged cholinergic enhancement in early Alzheimer's disease

Shanks, Michael F.; McGeown, William J.; Forbes-McKay, Katrina; Waiter, Gordon D.; Ries, Mario; Venneri, Annalena

doi:10.1016/j.mri.2007.02.005

Cited by 38 publications

(24 citation statements)

References 41 publications

(51 reference statements)

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“…The evidence from this exploratory fMRI study of AD patients receiving rivastigmine treatment for a clinically relevant period supports the conclusions from a similar study using galantamine (Shanks et al 2007). Variable patient response to treatment and drug dynamic and kinetic factors in small groups of patients studied with fMRI will inevitably bias (either way) the effect size of any relevant drug related changes in BOLD signal.…”

Section: Resultssupporting

confidence: 76%

“…Only one study has reported effects on brain activation following treatment with galantamine for a period comparable with the brain blood fl ow and metabolism studies. There was a modest restoration of regional task relevant brain activation for both the fMRI paradigms (testing semantic and attention skills) used, which was paralleled by a minor, statistically not signifi cant, improvement in behavioral scores (Shanks et al 2007). This research evidence fl ags up the importance of taking into account a pharmacokinetic trajectory, which may be uniquely characteristic of a given ChEI, in order to establish the time course of measurable effects on the chosen brain parameters and to better ensure that imaging variables represent a valid surrogate outcome measure of drug effi cacy in AD.…”

Section: Introductionmentioning

confidence: 91%

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Prolonged cholinergic enrichment influences regional cortical activation in early Alzheimer’s disease

McGeown

Shanks

Venneri

2008

NDT

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Neuroimaging studies of cholinesterase inhibitor (ChEI) treatment in Alzheimer's disease (AD) indicate that the short and long term actions of ChEIs are dissimilar. fMRI studies of the ChEI rivastigmine have focused on its short term action. In this exploratory study the effect of prolonged (20 weeks) rivastigmine treatment on regional brain activity was measured with fMRI in patients with mild AD. Eleven patients with probable AD and nine age-matched controls were assessed with a Pyramids and Palm Trees semantic association and an n-back working memory fMRI paradigm. In the patient group only, the assessment was repeated after 20 weeks of treatment. There was an increase in task-related brain activity after treatment with activations more like those of normal healthy elderly. Behaviorally, however, there were no signifi cant differences between baseline and retest scores, with a range of performance probably refl ecting variation in drug effi cacy across patients. Variable patient response and drug dynamic/kinetic factors in small patient groups will inevitably bias (either way) the effect size of any relevant drug related changes in activation. Future studies should take drug response into account to provide more insight into the benefi ts of ChEI drugs at the individual level.

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Section: Resultssupporting

confidence: 76%

Section: Introductionmentioning

confidence: 91%

Prolonged cholinergic enrichment influences regional cortical activation in early Alzheimer’s disease

McGeown

Shanks

Venneri

2008

NDT

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“…Several studies in healthy young and older subjects suggest that fMRI can detect acute pharmacological effects on memory networks (Thiel et al 2001;Sperling et al 2002;Kukolja et al 2009). To date, only a few small fMRI studies have shown enhanced brain activation after acute or prolonged treatment with cholinesterase inhibitors in MCI and AD, although these studies were not conducted as typical double-blind, placebocontrolled trials (Rombouts et al 2002;Goekoop et al 2004;Saykin et al 2004;Shanks et al 2007;Bokde et al 2009;Venneri et al 2009). fMRI is now being incorporated into a small number of investigator-initiated add-on studies to ongoing Phase II and Phase III trials, which should provide some valuable information regarding the potential utility of these techniques in clinical trials.…”

Section: Utility Of Functional Mri In the Study Of Admentioning

confidence: 99%

Brain Imaging in Alzheimer Disease

Johnson

Fox²,

Sperling³

et al. 2012

Cold Spring Harbor Perspectives in Medicine

535

375

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“…Although drug-induced modulation of memoryrelated networks have been detected by fMRI [240], only few studies have demonstrated abnormal activation following, for example, long-term treatment with cholinesterase inhibitors in MCI and AD [241][242][243][244]. Therfore, additional studies are needed to test the potential role of fMRI as biomarker in clinical trials [245].…”

Section: Functional Mri Markersmentioning

confidence: 99%

Perspective on future role of biological markers in clinical therapy trials of Alzheimer's disease: A long-range point of view beyond 2020

Hampel

Lista

Teipel

et al. 2014

Biochemical Pharmacology

102

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Recent advances in understanding the molecular mechanisms underlying various paths toward the pathogenesis of Alzheimer's disease (AD) has begun to provide new insight for interventions to modify disease progression. The evolving knowledge gained from multidisciplinary basic research has begun to identify new concepts for treatments and distinct classes of therapeutic targets; as well as putative disease-modifying compounds that are now being tested in clinical trials. There is a mounting consensus that such disease modifying compounds and/or interventions are more likely to be effectively administered as early as possible in the cascade of pathogenic processes preceding and underlying the clinical expression of AD. The budding sentiment is that "treatments" need to be applied before various molecular mechanisms converge into an irreversible pathway leading to morphological, metabolic and functional alterations that characterize the pathophysiology of AD. In light of this, biological indicators of pathophysiological mechanisms are desired to chart and detect AD throughout the asymptomatic early molecular stages into the prodromal and early dementia phase. A major conceptual development in the clinical AD research field was the recent proposal of new diagnostic criteria, which specifically incorporate the use of biomarkers as defining criteria for preclinical stages of AD. This paradigm shift in AD definition, conceptualization, operationalization, detection and diagnosis represents novel fundamental opportunities for the modification of interventional trial designs. This perspective summarizes not only present knowledge regarding biological markers but also unresolved questions on the status of surrogate indicators for detection of the disease in asymptomatic people and diagnosis of AD

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Regional brain activity after prolonged cholinergic enhancement in early Alzheimer's disease

Cited by 38 publications

References 41 publications

Prolonged cholinergic enrichment influences regional cortical activation in early Alzheimer’s disease

Prolonged cholinergic enrichment influences regional cortical activation in early Alzheimer’s disease

Brain Imaging in Alzheimer Disease

Perspective on future role of biological markers in clinical therapy trials of Alzheimer's disease: A long-range point of view beyond 2020

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Regional brain activity after prolonged cholinergic enhancement in early Alzheimer's disease

Cited by 38 publications

References 41 publications

Prolonged cholinergic enrichment influences regional cortical activation in early Alzheimer&rsquo;s disease

Prolonged cholinergic enrichment influences regional cortical activation in early Alzheimer&rsquo;s disease

Brain Imaging in Alzheimer Disease

Perspective on future role of biological markers in clinical therapy trials of Alzheimer's disease: A long-range point of view beyond 2020

Contact Info

Product

Resources

About

Prolonged cholinergic enrichment influences regional cortical activation in early Alzheimer’s disease

Prolonged cholinergic enrichment influences regional cortical activation in early Alzheimer’s disease