Hostname: page-component-78c5997874-dh8gc Total loading time: 0 Render date: 2024-11-05T02:10:30.188Z Has data issue: false hasContentIssue false
  • English
  • Français

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

Published online by Cambridge University Press:  29 October 2013

Krista L. Lanctôt ,
Sarah A. Chau ,
Nathan Herrmann ,
Lea T. Drye ,
Paul B. Rosenberg ,
Roberta W. Scherer ,
Sandra E. Black ,
Vijay Vaidya ,
David L. Bachman  and
Jacobo E. Mintzer
Krista L. Lanctôt*
Affiliation:
Departments of Psychiatry and Medicine (Neurology), and Brain Sciences Research Program, Sunnybrook Research Institute, Departments of Psychiatry, Pharmacology/Toxicology and Medicine (Neurology), University of Toronto, Ontario, Canada
Sarah A. Chau
Affiliation:
Departments of Psychiatry and Medicine (Neurology), and Brain Sciences Research Program, Sunnybrook Research Institute, Departments of Psychiatry, Pharmacology/Toxicology and Medicine (Neurology), University of Toronto, Ontario, Canada
Nathan Herrmann
Affiliation:
Departments of Psychiatry and Medicine (Neurology), and Brain Sciences Research Program, Sunnybrook Research Institute, Departments of Psychiatry, Pharmacology/Toxicology and Medicine (Neurology), University of Toronto, Ontario, Canada
Lea T. Drye
Affiliation:
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
Paul B. Rosenberg
Affiliation:
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Roberta W. Scherer
Affiliation:
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
Sandra E. Black
Affiliation:
Departments of Psychiatry and Medicine (Neurology), and Brain Sciences Research Program, Sunnybrook Research Institute, Departments of Psychiatry, Pharmacology/Toxicology and Medicine (Neurology), University of Toronto, Ontario, Canada
Vijay Vaidya
Affiliation:
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
David L. Bachman
Affiliation:
Department of Neurosciences, Alzheimer's Research and Clinical Programs, Medical University of South Carolina, SC, USA Ralph H. Johnson VA Medical Center, SC, USA
Jacobo E. Mintzer
Affiliation:
Department of Neurosciences, Alzheimer's Research and Clinical Programs, Medical University of South Carolina, SC, USA Ralph H. Johnson VA Medical Center, SC, USA
*
Correspondence should be addressed to: Krista L. Lanctôt, 2075 Bayview Avenue Room FG-08, Toronto, Ontario M4N 3M5, Canada. Fax: (1)416-480-6022. Email: [email protected].
Get access Rights & Permissions [Opens in a new window]

Abstract

Background:

Little is known about the effect of methylphenidate (MPH) on attention in Alzheimer's disease (AD). MPH has shown to improve apathy in AD, and both apathy and attention have been related to dopaminergic function. The goal was to investigate MPH effects on attention in AD and assess the relationship between attention and apathy responses.

Methods:

MPH (10 mg PO twice daily) or placebo was administered for six weeks in a randomized, double-blind trial in mild-to-moderate AD outpatients with apathy (Neuropsychiatric Inventory (NPI) Apathy ≥ 4). Attention was measured with the Wechsler Adult Intelligence Scale – Digit Span (DS) subtest (DS forward, selective attention) and apathy with the Apathy Evaluation Scale (AES). A mixed effects linear regression estimated the difference in change from baseline between treatment groups, defined as δ (MPH (DS week 6–DS baseline)) – (placebo (DS week 6–DS baseline)).

Results:

In 60 patients (37 females, age = 76 ± 8, Mini-Mental State Examination (MMSE) = 20 ± 5, NPI Apathy = 7 ± 2), the change in DS forward (δ = 0.87 (95% CI: 0.06–1.68), p = 0.03) and DS total (δ = 1.01 (95% CI: 0.09–1.93), p = 0.03) favored MPH over placebo. Of 57 completers, 17 patients had improved apathy (≥3.3 points on the AES from baseline to end point) and 40 did not. There were no significant associations between AES and NPI Apathy with DS change scores in the MPH, placebo, AES responder, or non-responder groups. DS scores did not predict apathy response to MPH treatment.

Conclusion:

These results suggest MPH can improve attention and apathy in AD; however, the effects appear independent in this population.

Keywords

Alzheimer's diseaseapathyneuropharmacologypsychopharmacologybehavioral and psychological symptoms of dementia (BPSD)
Type
Research Article
Information
International Psychogeriatrics , Volume 26 , Issue 2 , February 2014 , pp. 239 - 246
Copyright
Copyright © International Psychogeriatric Association 2013 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Auriel, E., Hausdorff, J. M., Herman, T., Simon, E. S. and Giladi, N. (2006). Effects of methylphenidate on cognitive function and gait in patients with Parkinson's disease: a pilot study. Clinical Neuropharmacology, 29, 15–17.Google Scholar
Baddeley, A. D., Logie, R., Bressi, S., Della Sala, S. and Spinnler, H. (1986). Dementia and working memory. Quarterly Journal of Experimental Psychology, 38, 603–618.CrossRefGoogle ScholarPubMed
Berridge, C. W. and Devilbiss, D. M. (2011). Psychostimulants as cognitive enhancers: the prefrontal cortex, catecholamines, and attention-deficit/hyperactivity disorder. Biological Psychiatry, 69, e101–111.Google Scholar
Bronnick, K.et al. (2006). Attentional deficits affect activities of daily living in dementia-associated with Parkinson's disease. Journal of Neurology, Neurosurgery and Psychiatry, 77, 1136–1142.CrossRefGoogle ScholarPubMed
Cools, R. and D'Esposito, M. (2011). Inverted-U-shaped dopamine actions on human working memory and cognitive control. Biological Psychiatry, 69, e113–125.CrossRefGoogle ScholarPubMed
Cools, R., Frank, M. J., Gibbs, S. E., Miyakawa, A., Jagust, W. and D'Esposito, M. (2009). Striatal dopamine predicts outcome-specific reversal learning and its sensitivity to dopaminergic drug administration. Journal of Neuroscience, 29, 1538–1543.Google Scholar
Cross, A. J., Crow, T. J., Ferrier, I. N., Johnson, J. A. and Markakis, D. (1984). Striatal dopamine receptors in Alzheimer-type dementia. Neuroscience Letters, 52, 1–6.Google Scholar
Cummings, J. L., Mega, M. S., Gray, K., Rosenberg-Thompson, S., Carusi, D. A. and Gornbein, J. (1994). Neuropsychiatric inventory: comprehensive assessment of psychopathology in dementia. Neurology, 44, 2308–2314.Google Scholar
David, R.et al. (2008). Striatal dopamine transporter levels correlate with apathy in neurodegenerative diseases: a SPECT study with partial volume effect correction. Clinical Neurology and Neurosurgery, 110, 19–24.Google Scholar
Drye, L. T.et al. (2013). Designing a trial to evaluate potential treatments for apathy in dementia: the Apathy in Dementia Methylphenidate Trial (ADMET). American Journal of Geriatric Psychiatry, 21, 549–559.CrossRefGoogle ScholarPubMed
Folstein, M. F., Folstein, S. E. and McHugh, P. R. (1975). “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research, 12, 189–198.CrossRefGoogle ScholarPubMed
Galvin, J. E.et al. (2008). Effects of galantamine on measures of attention: results from 2 clinical trials in Alzheimer disease patients with comparisons to donepezil. Alzheimer Disease and Associated Disorders, 22, 30–38.Google Scholar
Galynker, I., Ieronimo, C., Miner, C., Rosenblum, J., Vilkas, N. and Rosenthan, R. (1997). Methylphenidate treatment of negative symptoms in patients with dementia. Journal of Neuropsychiatry and Clinical Neurosciences, 9, 231–239.Google ScholarPubMed
Gorus, E., Lambert, M., De Raedt, R. and Mets, T. (2007). The influence of galantamine on reaction time, attention processes, and performance variability in elderly Alzheimer patients. Journal of Clinical Psychopharmacology, 27, 182–187.Google Scholar
Hendrix, S. B. and Welsh-Bohmer, K. A. (2013). Separation of cognitive domains to improve prediction of progression from mild cognitive impairment to Alzheimer's disease. Alzheimer's Research and Therapy, 5, 22.CrossRefGoogle ScholarPubMed
Herrmann, N.et al. (2008). Methylphenidate for the treatment of apathy in Alzheimer disease: prediction of response using dextroamphetamine challenge. Journal of Clinical Psychopharmacology, 28, 296–301.Google Scholar
Ivanov, I.et al. (2012). Effects of motivation on reward and attentional networks: an fMRI study. Brain Behavior, 2, 741–753.Google Scholar
Koob, G. F. (1996). Hedonic valence, dopamine and motivation. Molecular Psychiatry, 1, 186–189.Google Scholar
Kuczenski, R., Segal, D. S., Cho, A. K. and Melega, W. (1995). Hippocampus norepinephrine, caudate dopamine and serotonin, and behavioral responses to the stereoisomers of amphetamine and methylphenidate. Journal of Neuroscience, 15, 1308–1317.Google Scholar
Lanctôt, K. L.et al. (2007). A SPECT study of apathy in Alzheimer's disease. Dementia and Geriatric Cognitive Disorders, 24, 65–72.CrossRefGoogle ScholarPubMed
Lanctôt, K. L.et al. (2008). Apathy associated with Alzheimer disease: use of dextroamphetamine challenge. American Journal of Geriatric Psychiatry, 16, 551–557.Google Scholar
Marin, R. S., Biedrzycki, R. C. and Firinciogullari, S. (1991). Reliability and validity of the Apathy Evaluation Scale. Psychiatry Research, 38, 143–162.Google Scholar
McGuinness, B., Barrett, S. L., Craig, D., Lawson, J. and Passmore, A. P. (2010). Attention deficits in Alzheimer's disease and vascular dementia. Journal of Neurology, Neurosurgery And Psychiatry, 81, 157–159.Google Scholar
McPherson, S., Fairbanks, L., Tiken, S., Cummings, J. L. and Back-Madruga, C. (2002). Apathy and executive function in Alzheimer's disease. Journal of the International Neuropsychological Society, 8, 373–381.Google Scholar
Mitchell, R. A., Herrmann, N. and Lanctôt, K. L. (2010). The role of dopamine in symptoms and treatment of apathy in Alzheimer's disease. CNS Neuroscience and Therapeutics, 17, 411–427.CrossRefGoogle ScholarPubMed
Nieoullon, A. and Coquerel, A. (2003). Dopamine: a key regulator to adapt action, emotion, motivation and cognition. Current Opinion in Neurology, 16 (Suppl. 2), S3–9.CrossRefGoogle ScholarPubMed
Padala, P. R.et al. (2010). Methylphenidate for apathy and functional status in dementia of the Alzheimer type. American Journal of Geriatric Psychiatry, 18, 371–374.Google Scholar
Park, L. Q.et al. (2012). Confirmatory factor analysis of the ADNI Neuropsychological Battery. Brain Imaging and Behavior, 6, 528–539.Google Scholar
Perry, R. J. and Hodges, J. R. (1999). Attention and executive deficits in Alzheimer's disease. A critical review. Brain, 122 (Pt 3), 383–404.CrossRefGoogle ScholarPubMed
Perry, R. J., Watson, P. and Hodges, J. R. (2000). The nature and staging of attention dysfunction in early (minimal and mild) Alzheimer's disease: relationship to episodic and semantic memory impairment. Neuropsychologia, 38, 252–271.CrossRefGoogle ScholarPubMed
Rapp, M. A. and Reischies, F. M. (2005). Attention and executive control predict Alzheimer disease in late life: results from the Berlin Aging Study (BASE). American Journal of Geriatric Psychiatry, 13, 134–141.Google Scholar
Rosenberg, P. B.et al. (2013). Safety and efficacy of methylphenidate for apathy in Alzheimer's disease: a randomized, placebo-controlled trial. Journal of Clinical Psychiatry, 74, 810–816.Google Scholar
Schneider, L. S.et al. (1997). Validity and reliability of the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change. The Alzheimer's Disease Cooperative Study. Alzheimer Disease and Associated Disorders, 11, S22–32.CrossRefGoogle ScholarPubMed
Storga, D., Vrecko, K., Birkmayer, J. G. and Reibnegger, G. (1996). Monoaminergic neurotransmitters, their precursors and metabolites in brains of Alzheimer patients. Neuroscience Letters, 203, 29–32.Google Scholar
Swanson, J.et al. (1999). Acute tolerance to methylphenidate in the treatment of attention deficit hyperactivity disorder in children. Clinical Pharmacology and Therapeutics, 66, 295–305.Google Scholar
Tucha, O., Mecklinger, L., Laufkotter, R., Klein, H. E., Walitza, S. and Lange, K. W. (2006). Methylphenidate-induced improvements of various measures of attention in adults with attention deficit hyperactivity disorder. Journal of Neural Transmission, 113, 1575–1592.CrossRefGoogle ScholarPubMed
Vellas, B.et al. (2005). Early onset effects of galantamine treatment on attention in patients with Alzheimer's disease. Current Medical Research and Opinion, 21, 1423–1429.Google Scholar
Wheeler, D. (1981). Wechsler Adult Intelligence Scale–Revised, Manual. New York: Psychological Corporation.Google Scholar