Decline in prefrontal catecholamine synthesis explains age-related changes in cognitive speed beyond regional grey matter atrophy.
OBJECTIVE
Age-related decline in cognitive speed has been associated with prefrontal dopamine D1 receptor availability, but the contribution of presynaptic dopamine and noradrenaline innervation to age-related changes in cognition is unknown.


METHODS
In a group of 16 healthy participants aged 22-61 years, we used PET and the radioligand FDOPA to measure catecholamine synthesis capacity (K (in) (app); millilitres per gram per minute) and the digit symbol substitution test to measure cognitive speed, a component of fluid IQ.


RESULTS
Cognitive speed was associated with the magnitude of K (in) (app) in the prefrontal cortex (p < 0.0005). Both cognitive speed (p = 0.003) and FDOPA K (in) (app) (p < 0.0005) declined with age, both in a standard voxel-wise analysis and in a volume-of-interest analysis with partial volume correction, and the correlation between cognitive speed and K (in) (app) remained significant beyond the effects of age (p = 0.047). MR-based segmentation revealed that these age-related declines were not attributable to age-related alterations in grey matter density.


CONCLUSIONS
Our findings indicate that age-related changes in the capacity of the prefrontal cortex to synthesize catecholamines, irrespective of cortical atrophy, may underlie age-related decline in cognitive speed.
Department of Psychiatry and Psychotherapy, Campus Mitte, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany. jan.kalbitzer@charite.de
Jan
J
Kalbitzer
Lorenz
L
Deserno
Florian
F
Schlagenhauf
Anne
A
Beck
Thomas
T
Mell
Gerd
G
Bahr
Hans-Georg
HG
Buchholz
Michail
M
Plotkin
Ralph
R
Buchert
Yoshitaka
Y
Kumakura
Paul
P
Cumming
Andreas
A
Heinz
Michael A
MA
Rapp
D000328:Adult; D000375:Aging / Q000378:metabolism* / Q000502:physiology; D001284:Atrophy / Q000378:metabolism / Q000503:physiopathology; D003071:Cognition / Q000502:physiology*; D004298:Dopamine / Q000096:biosynthesis*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000378:metabolism* / Q000473:pathology* / Q000502:physiology; D013997:Time Factors; D055815:Young Adult
D004298:Dopamine