ReviewThe American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry2021
Neurobiologic Rationale for Treatment of Apathy in Alzheimer's Disease With Methylphenidate.
Review in The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 3 syntheses or guidelines pooled it, 42 citations in OpenAlex.
- Mapping new pharmacological interventions for cognitive function in Alzheimer's disease: a systematic review of randomized clinical trials.Frontiers in pharmacology · 2023Pooled it
- Efficacy of methylphenidate for the treatment of apathy in patients with Alzheimer's disease: a systematic review and meta-analysis of randomized controlled studies.Psychopharmacology · 2022Pooled it
- Cerebral Volumetric Correlates of Apathy in Alzheimer's Disease and Cognitively Normal Older Adults: Meta-Analysis, Label-Based Review, and Study of an Independent Cohort.Journal of Alzheimer's disease : JAD · 2022Pooled it
- Correlation between changes in apathy and cognition in Alzheimer's disease associated apathy: Analysis of the Apathy in Dementia Methylphenidate Trial 2 (ADMET 2).International psychogeriatrics · 2025Trial
- Depression in neurodegenerative disease: neurobiological mechanisms and emerging treatments.Molecular psychiatry · 2026Review
- Loss of neuronal population organization links pathology to behavior in a model of Alzheimer's disease.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Bilateral DLPFC transcranial direct current stimulation for mood and motor symptoms in Parkinson's disease: a preliminary study.Acta neuropsychiatrica · 2026Article
- Targeting central immune signaling enhances the effects of methylphenidate in alleviating apathy-like behavior in 5xFAD mice.Scientific reports · 2026Article
- Loss of neuronal population organization links pathology to behavior in a model of Alzheimer's disease.bioRxiv : the preprint server for biology · 2026Article
- Targeting central immune signaling enhances the effects of methylphenidate in alleviating apathy-like behavior in 5xFAD mice.Research square · 2025Article
- From copper homeostasis to cuproptosis: a new perspective on CNS immune regulation and neurodegenerative diseases.Frontiers in neurology · 2025Review
- Advances in the study of apathy related to cerebral small vessel disease.Frontiers in neurology · 2025Review
- Treatment of Apathy in Parkinson's Disease and Implications for Underlying Pathophysiology.Journal of clinical medicine · 2024Review
- Cerebrospinal fluid amyloid-β and cerebral microbleed are associated with distinct neuropsychiatric sub-syndromes in cognitively impaired patients.Alzheimer's research & therapy · 2024Article
- Heterogeneity of Response to Methylphenidate in Apathetic Patients in the ADMET 2 Trial.The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry · 2023Article
- Cognitive, Disability, and Treatment Outcome Implications of Symptom-Based Phenotyping in Late-Life Depression.The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry · 2023Article
- Distinguishing apathy from depression: A review differentiating the behavioral, neuroanatomic, and treatment-related aspects of apathy from depression in neurocognitive disorders.International journal of geriatric psychiatry · 2023Review
- The neurobiology of apathy in depression and neurocognitive impairment in older adults: a review of epidemiological, clinical, neuropsychological and biological research.Translational psychiatry · 2022Review
- Cognitive and neuropsychiatric effects of noradrenergic treatment in Alzheimer's disease: systematic review and meta-analysis.Journal of neurology, neurosurgery, and psychiatry · 2022Article
- Pharmacological Management of Apathy in Dementia.CNS drugs · 2022Review
Corrections and comments
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Authors and funding
13 authors at 9 institutions in 2 countries.
Funding
Abstract
The public health burden of Alzheimer's disease (AD) is related not only to cognitive symptoms, but also to neuropsychiatric symptoms, including apathy. Apathy is defined as a quantitative reduction of goal-directed activity in comparison to a previous level of functioning and affects 30%-70% of persons with AD. Previous attempts to treat apathy in AD-both nonpharmacologically and pharmacologically-have been wanting. Catecholaminergic treatment with methylphenidate has shown encouraging results in initial trials of apathy in AD. Understanding the neuronal circuits underlying motivated behavior and their reliance on catecholamine actions helps provide a rationale for methylphenidate actions in the treatment of apathy in patients with AD. Anatomical, physiological, and behavioral studies have identified parallel, cortical-basal ganglia circuits that govern action, cognition, and emotion and play key roles in motivated behavior. Understanding the distinct contributions to motivated behavior of subregions of the prefrontal cortex-dorsolateral, orbital-ventromedial, and dorsomedial-helps to explain why degeneration of these areas in AD results in apathetic behaviors. We propose that the degeneration of the prefrontal cortex in AD produces symptoms of apathy. We further propose that methylphenidate treatment may ameliorate those symptoms by boosting norepinephrine and dopamine actions in prefrontal-striatal-thalamocortical circuits.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.