Relative lack of cognitive effects of methylphenidate in elderly male volunteers.
BACKGROUND
Methylphenidate, a dopaminergic and noradrenergic reuptake inhibitor, has been shown in young, healthy adult volunteers to produce pronounced effects on working memory and sustained attention. We were interested in assessing whether similar improvements could be conferred upon elderly volunteers in order to gain a more complete understanding of the effects of age on monoaminergic manipulations of working memory and attention, as well as to explore the potential for pharmacological intervention in attention and executive dysfunction disorders in this age group.


OBJECTIVE
The main aim of the study was to characterise the dose-related effects of methylphenidate on a range of neuropsychological functions in elderly healthy volunteers.


METHODS
Sixty healthy elderly adult male volunteers received either a single oral dose of placebo, 20 mg or 40 mg methylphenidate prior to performing a variety of tasks designed to assess memory, attention and executive function. A randomised double-blind, between-subjects design was used.


RESULTS
Methylphenidate had significant cardiovascular and subjective effects. However, unlike in younger volunteers, no significant effects of drug on working memory (spatial span and spatial working memory), response inhibition (stop-signal) or sustained attention (rapid visual information processing) were seen. Subtle effects on latency similar to those in younger volunteers were identified: both doses of methylphenidate resulted in a slowing in response time during set-shifting and decision-making.


CONCLUSIONS
The results of this study demonstrate that, in elderly subjects, the cognitive effects of methylphenidate are grossly attenuated and distinct from the profile previously described in younger volunteers. It is suggested that methylphenidate may not be appropriate as a pharmacological intervention in elderly patient groups, such as those reporting age-related cognitive decline.
Department of Psychiatry, University of Cambridge, School of Clinical Medicine, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK.
Danielle C
DC
Turner
Trevor W
TW
Robbins
Luke
L
Clark
Adam R
AR
Aron
Jonathan
J
Dowson
Barbara J
BJ
Sahakian
D000284:Administration, Oral; D000367:Age Factors; D000368:Aged; D002320:Cardiovascular Physiological Phenomena / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects; D003071:Cognition / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D008875:Middle Aged; D009483:Neuropsychological Tests; D010147:Pain Measurement / Q000187:drug effects; D011930:Reaction Time / Q000187:drug effects; D012307:Risk Factors
D008774:Methylphenidate