Dopamine treatment and cognitive functioning in individuals with Parkinson's disease: the "cognitive flexibility" hypothesis seems to work.
BACKGROUND
Previous data suggest that (i) dopamine modulates the ability to implement nonroutine schemata and update operations (flexibility processes) and that (ii) dopamine-related improvement may be related to baseline dopamine levels in target pathways (inverted U-shaped hypothesis).


OBJECTIVE
To investigate above hypotheses in individuals with Parkinson's disease (PD).


METHODS
Twenty PD patients were administered tasks varying as to flexibility load in two treatment conditions: (i) "off" condition, about 18 hours after dopamine dose and (ii) "on" condition, after dopamine administration. PD patients were separated into two groups: low performers (i.e., performance on Digit Span Backward below the sample mean) and high performers (i.e., performance above the mean). Twenty healthy individuals performed the tasks in two sessions without taking drugs.


RESULTS
Passing from the "off" to the "on" state, only low performer PD patients significantly improved their performance on high-flexibility measures (interference condition of the Stroop test; P < 0.05); no significant effect was found on low-flexibility tasks.


CONCLUSIONS
These findings document that high-flexibility processes are sensitive to dopamine neuromodulation in the early phases of PD. This is in line with the hypothesis that striatal dopamine pathways, affected early by PD, are precociously implicated in the expression of cognitive disorders in these individuals.
I.R.C.C.S. Santa Lucia Foundation, Via Ardeatina 306, 00179 Rome, Italy.
Alberto
A
Costa
I.R.C.C.S. Santa Lucia Foundation, Via Ardeatina 306, 00179 Rome, Italy.
Antonella
A
Peppe
I.R.C.C.S. Santa Lucia Foundation, Via Ardeatina 306, 00179 Rome, Italy.
Ilenia
I
Mazzù
I.R.C.C.S. Santa Lucia Foundation, Via Ardeatina 306, 00179 Rome, Italy.
Mariachiara
M
Longarzo
I.R.C.C.S. Santa Lucia Foundation, Via Ardeatina 306, 00179 Rome, Italy ; Clinical Neurology, University of Rome, "Tor Vergata", Via Orazio Raimondo 18, 00173 Rome, Italy.
Carlo
C
Caltagirone
I.R.C.C.S. Santa Lucia Foundation, Via Ardeatina 306, 00179 Rome, Italy ; Clinical Neurology, University of Rome, "Tor Vergata", Via Orazio Raimondo 18, 00173 Rome, Italy.
Giovanni A
GA
Carlesimo
D000368:Aged; D000978:Antiparkinson Agents / Q000494:pharmacology / Q000627:therapeutic use*; D003071:Cognition / Q000187:drug effects*; D005260:Female; D006801:Humans; D007980:Levodopa / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000188:drug therapy* / Q000523:psychology; D011930:Reaction Time / Q000187:drug effects; D016896:Treatment Outcome
D000978:Antiparkinson Agents; D007980:Levodopa