SPECT monitoring of improved cerebral blood flow during long-term treatment of elderly patients with nootropic drugs.
OBJECTIVE
In normal aging persons, oxygen and glucose consumption progressively decreases with reduced cerebral blood flow (CBF), which could be responsible for age-related changes in cognitive functions. A data processing model with the use of Tc-99m SPECT of the human brain has been developed and found to be sensitive for monitoring the effects of drugs that increase CBF. In this study, the effect of two vasodilator drugs (the combination of pentifylline and nicotinic acid versus piracetam) was compared with the effect of placebo on CBF.


METHODS
Thirty elderly volunteers had three different procedures using the Peelproc method to spatially standardize and compare CBF patterns by SPECT before and after drug intervention. The 30 patients were divided into five groups of six persons each who were randomly assigned in a 1:1 ratio to the treatment sequences consisting of three phases: the combination of pentifylline and nicotinic acid (C), piracetam (N), and placebo (P), or C-N-P; P-N-C; P-C-N; N-C-P; C-P-N; or N-P-C. Phases 1 to 3 each consisted of a baseline recording of parameters (day 0), treatment for 60 days (days 1 to 60), and recording of parameters after treatment (day 61).


RESULTS
In elderly human volunteers (ages, 52 to 70 years), after 2 months of oral treatment with a combination of pentifylline and nicotinic acid (800 mg pentifylline, 200 mg nicotinic acid daily), SPECT results for the Peel-proc program indicated a statistically significant improvement in CBF of the total brain, with a more pronounced improvement in the cerebellum and frontal regions, where a definite shift from abnormal to normal blood flow was detected. Spontaneous communication from most of the volunteers suggested that they experienced an improvement in memory and general well-being from the combination treatment. After 2 months of oral treatment with piracetam (2.4 g daily) in elderly human volunteers, SPECT results indicated a regional improvement in CBF, particularly in the cerebellum. However, no beneficial effects with this drug were spontaneously reported.


CONCLUSIONS
The in vivo method to quantitatively monitor the progress of long-term drug therapy on CBF described here could be useful to assess and even direct changes in therapy.
Dormehl
I C
IC
Atomic Energy Corporation, Institute for Life Sciences, University of Pretoria, Republic of South Africa. dormehl@medic.up.ac.za
Jordaan
B
B
Oliver
D W
DW
Croft
S
S
D000284:Administration, Oral; D000368:Aged; D000375:Aging / Q000502:physiology; D001921:Brain / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000378:metabolism; D002531:Cerebellum / Q000098:blood supply / Q000000981:diagnostic imaging; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D003071:Cognition / Q000187:drug effects / Q000502:physiology; D018592:Cross-Over Studies; D003704:Dementia / Q000188:drug therapy; D004338:Drug Combinations; D005625:Frontal Lobe / Q000098:blood supply / Q000000981:diagnostic imaging; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008569:Memory Disorders / Q000188:drug therapy; D008875:Middle Aged; D009525:Niacin / Q000008:administration & dosage / Q000627:therapeutic use; D018697:Nootropic Agents / Q000627:therapeutic use*; D010101:Oxygen Consumption; D017060:Patient Satisfaction; D010889:Piracetam / Q000008:administration & dosage / Q000627:therapeutic use; D010919:Placebos; D016037:Single-Blind Method; D013805:Theobromine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D015899:Tomography, Emission-Computed, Single-Photon; D014665:Vasodilator Agents / Q000627:therapeutic use
D004338:Drug Combinations; D018697:Nootropic Agents; D010919:Placebos; D014665:Vasodilator Agents; D009525:Niacin; D005947:Glucose; C007942:pentifylline; D013805:Theobromine; D010889:Piracetam