Long-term effects of the concomitant use of memantine with cholinesterase inhibition in Alzheimer disease.
BACKGROUND
Patients using cholinesterase inhibitors (ChEIs) have a delay in nursing home (NH) admission compared with those who were not using the medication. There are no long-term studies of the effects of memantine in combination with ChEIs use in Alzheimer disease (AD). This study was conducted to examine the effects of ChEIs and memantine on time to death and time to NH admission.


METHODS
Time to NH admission and death was examined in 943 probable AD patients who had at least a 1-year follow-up evaluation. Of these patients, 140 (14.9%) used both ChEIs and memantine, 387 (41%) [corrected] used only ChEIs, and 416 (44.1%) [corrected] used neither. The mean (SD) follow-up time was 62.3 (35.8) months. The analysis was conducted with multivariable Cox proportional hazard models controlling for critical covariates (ie, age, education level, gender, severity of the dementia, hypertension, diabetes mellitus, heart disease, psychiatric symptoms and use of psychotropic medications).


RESULTS
Compared with those who never used cognitive enhancers, patients who used ChEIs had a significant delay in NH admission (HR: 0.37, 95% CI 0.27 to 0.49); this effect was significantly augmented with the addition of memantine (HR: 0.29, 95% CI 0.11 to 0.72) (memantine+ChEI vs ChEI alone). ChEIs alone, or in combination with memantine had no significant association on time to death.


CONCLUSIONS
This observational study revealed that the addition of the NMDA receptor antagonist memantine to the treatment of AD with ChEI significantly altered the treated history of AD by extending time to nursing home admission.
Lopez
O L
OL
Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. lopezol@upmc.edu
Becker
J T
JT
Wahed
A S
AS
Saxton
J
J
Sweet
R A
RA
Wolk
D A
DA
Klunk
W
W
Dekosky
S T
ST
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000401:mortality; D002800:Cholinesterase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D018691:Excitatory Amino Acid Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006707:Homes for the Aged; D006801:Humans; D008297:Male; D008559:Memantine / Q000009:adverse effects / Q000627:therapeutic use*; D008609:Mental Status Schedule; D009483:Neuropsychological Tests; D018697:Nootropic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D009735:Nursing Homes; D010343:Patient Admission; D016019:Survival Analysis
D002800:Cholinesterase Inhibitors; D018691:Excitatory Amino Acid Antagonists; D018697:Nootropic Agents; D008559:Memantine