title: Effect of methylphenidate on attention in apathetic AD patients in a randomized, placebo-controlled trial.
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.
  
  
  CONCLUSIONS
  These results suggest MPH can improve attention and apathy in AD; however, the effects appear independent in this population.
authors.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.
authors.forename: Krista L
authors.initials: KL
authors.lastname: Lanctôt
authors.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.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Chau
authors.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.
authors.forename: Nathan
authors.initials: N
authors.lastname: Herrmann
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: Lea T
authors.initials: LT
authors.lastname: Drye
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Paul B
authors.initials: PB
authors.lastname: Rosenberg
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: Roberta W
authors.initials: RW
authors.lastname: Scherer
authors.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.
authors.forename: Sandra E
authors.initials: SE
authors.lastname: Black
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: Vijay
authors.initials: V
authors.lastname: Vaidya
authors.affiliation: Department of Neurosciences, Alzheimer's Research and Clinical Programs, Medical University of South Carolina, SC, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Bachman
authors.affiliation: Department of Neurosciences, Alzheimer's Research and Clinical Programs, Medical University of South Carolina, SC, USA.
authors.forename: Jacobo E
authors.initials: JE
authors.lastname: Mintzer
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis / Q000188:drug therapy / Q000523:psychology; D057565:Apathy / Q000187:drug effects*; D001288:Attention / Q000187:drug effects*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000009:adverse effects; D004311:Double-Blind Method; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000008:administration & dosage / Q000009:adverse effects; D009483:Neuropsychological Tests; D011569:Psychiatric Status Rating Scales; D016896:Treatment Outcome
chemical_list: D000697:Central Nervous System Stimulants; D008774:Methylphenidate