Effect of methylphenidate on attention in apathetic AD patients in a randomized, placebo-controlled trial

Lanctôt, Krista L.; Chau, Sarah; Herrmann, Nathan; Drye, Lea T.; Rosenberg, Paul B.; Scherer, Roberta W.; Black, Sandra E.; Vaidya, Vijay; Bachman, David; Mintzer, Jacobo

doi:10.1017/s1041610213001762

Cited by 40 publications

(35 citation statements)

References 38 publications

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“…The study, 133 however, was not specifi cally designed to assess apathy (Level U). These few fi ndings in Parkinson's disease are in line with double-blind, placebo-controlled studies [134][135][136] in Alzheimer's disease The following proposed criteria represent the views of the authors. They are intended to guide clinicians in making a diagnosis of apathy and in identifying appropriate treatments.…”

Section: Treatment Of Apathy In Parkinson's Diseasementioning

confidence: 55%

Apathy in Parkinson's disease: clinical features, neural substrates, diagnosis, and treatment

Pagonabarraga

Kulisevsky

Strafella

et al. 2015

The Lancet Neurology

405

394

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Normal maintenance of human motivation depends on the integrity of subcortical structures that link the prefrontal cortex with the limbic system. Structural and functional disruption of diff erent networks within these circuits alters the maintenance of spontaneous mental activity and the capacity of aff ected individuals to associate emotions with complex stimuli. The clinical manifestations of these changes include a continuum of abnormalities in goal-oriented behaviours known as apathy. Apathy is highly prevalent in Parkinson's disease (and across many neurodegenerative disorders) and can severely aff ect the quality of life of both patients and caregivers. Diff erentiation of apathy from depression, and discrimination of its cognitive, emotional, and auto-activation components could guide an individualised approach to the treatment of symptoms. The opportunity to manipulate dopaminergic treatment in Parkinson's disease allows researchers to study a continuous range of motivational states, from apathy to impulse control disorders. Parkinson's disease can thus be viewed as a model that provides insight into the neural substrates of apathy.

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Section: Treatment Of Apathy In Parkinson's Diseasementioning

confidence: 55%

Apathy in Parkinson's disease: clinical features, neural substrates, diagnosis, and treatment

Pagonabarraga

Kulisevsky

Strafella

et al. 2015

The Lancet Neurology

405

394

View full text Add to dashboard Cite

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“…Unfortunately, few controlled trials target treatment of apathy in AD. One recent randomized placebo-controlled trial of methylphenidate for apathy in AD (ADMET) reported improvement in two out of three efficacy outcomes with a trend toward improved global cognition with minimal adverse events [ 81 - 83 ]. Few other uncontrolled trials, however, have also shown treatment effects with methylphenidate [ 84 , 85 ] and one with donepezil [ 86 ].…”

Section: Management Of Common Neuropsychiatric Syndromes In Alzheimermentioning

confidence: 99%

Principles and management of neuropsychiatric symptoms in Alzheimer’s dementia

2015

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Neuropsychiatric symptoms of Alzheimer’s disease (NPS-AD) are highly prevalent and lead to poor medical and functional outcomes. In spite of the burdensome nature of NPS-AD, we are continuing to refine the nosology and only beginning to understand the underlying pathophysiology. Cluster analyses have frequently identified three to five subsyndromes of NPS-AD: behavioral dysfunction (for example, agitation/aggressiveness), psychosis (for example, delusions and hallucinations), and mood disturbance (for example, depression or apathy). Recent neurobiological studies have used new neuroimaging techniques to elucidate behaviorally relevant circuits and networks associated with these subsyndromes. Several fronto-subcortical circuits, cortico-cortical networks, and neurotransmitter systems have been proposed as regions and mechanisms underlying NPS-AD. Common to most of these subsyndromes is the broad overlap of regions associated with the salience network (anterior cingulate and insula), mood regulation (amygdala), and motivated behavior (frontal cortex). Treatment strategies for dysregulated mood syndromes (depression and apathy) have primarily targeted serotonergic mechanisms with antidepressants or dopaminergic mechanisms with psychostimulants. Psychotic symptoms have largely been targeted with anti-psychotic medications despite controversial risk/benefit tradeoffs. Management of behavioral dyscontrol, including agitation and aggression in AD, has encompassed a wide range of psychoactive medications as well as non-pharmacological approaches. Developing rational therapeutic approaches for NPS-AD will require a firmer understanding of the underlying etiology in order to improve nosology as well as provide the empirical evidence necessary to overcome regulatory and funding challenges to further study these debilitating symptoms.

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“…Methylphenidate may improve executive functioning by increasing norepinephrine and dopamine concentrations in the synaptic cleft [6]. While some studies in patients with dementia due to Alzheimer's disease (AD) have suggested an effect of methylphenidate on global cognition and on attention [7][8][9][10], other studies have not consistently supported the results [11]. In patients with VCI, only 1 small older open label longitudinal study in 15 patients with dementia found that methylphenidate slightly improved scores on the Mini-Mental State Examination (MMSE) [12].…”

Section: Introductionmentioning

confidence: 99%

Methylphenidate and galantamine in patients with vascular cognitive impairment–the proof-of-principle study STREAM-VCI

et al. 2020

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Background: To date, no symptomatic treatment is available for patients with vascular cognitive impairment (VCI). In the proof-of-principle study Symptomatic Treatment of Vascular Cognitive Impairment (STREAM-VCI), we investigated whether a single dose of a monoaminergic drug (methylphenidate) improves executive functioning and whether a single dose of a cholinergic drug (galantamine) improves memory in VCI patients. Methods: STREAM-VCI is a single-center, double-blind, three-way crossover trial. We included 30 VCI patients (Mini-Mental State Examination (MMSE) ≥ 16 and Clinical Dementia Rating score 0.5-1.0) with cerebrovascular pathology on MRI. All patients received single doses of methylphenidate (10 mg), galantamine (16 mg), and placebo in random order on three separate study visits. We used the NeuroCart®, a computerized test battery, to assess drug-sensitive cognitive effects. Predefined main outcomes, measured directly after a single dose of a study drug, were (i) change in performance on the adaptive tracker for executive functioning and (ii) performance on the Visual Verbal Learning Test-15 (VVLT-15) for memory, compared to placebo. We performed mixed model analysis of variance. Results: The study population had a mean age of 67 ± 8 years and MMSE 26 ± 3, and 9 (30%) were female. Methylphenidate improved performance on the adaptive tracker more than placebo (mean difference 1.40%; 95% confidence interval [CI] 0.56-2.25; p = 0.002). In addition, methylphenidate led to better memory performance on the VVLT-15 compared to placebo (mean difference in recalled words 0.59; 95% CI 0.03-1.15; p = 0.04). Galantamine did not improve performance on the adaptive tracker and led to worse performance on delayed recall of the VVLT-15 (mean difference − 0.84; 95% CI − 1.65, − 0.03; p = 0.04). Methylphenidate was well tolerated while galantamine produced gastrointestinal side effects in a considerable number of patients. Conclusions: In this proof-of-principle study, methylphenidate is well tolerated and improves executive functioning and immediate recall in patients with VCI. Galantamine did not improve memory or executive dysfunction. Results might be influenced by the considerable amount of side effects seen. Trial registration: http://www.clinicaltrials.gov. Registration number: NCT02098824. Registration date: March 28, 2014.

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Effect of methylphenidate on attention in apathetic AD patients in a randomized, placebo-controlled trial

Cited by 40 publications

References 38 publications

Apathy in Parkinson's disease: clinical features, neural substrates, diagnosis, and treatment

Apathy in Parkinson's disease: clinical features, neural substrates, diagnosis, and treatment

Principles and management of neuropsychiatric symptoms in Alzheimer’s dementia

Methylphenidate and galantamine in patients with vascular cognitive impairment–the proof-of-principle study STREAM-VCI

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