Effects of centrally acting angiotensin converting enzyme inhibitors on functional decline in patients with Alzheimer's disease.
BACKGROUND
Centrally acting angiotensin converting enzyme inhibitors (CACE-Is) are associated with reduced rates of cognitive decline in patients with dementia. CACE-Is may also improve exercise tolerance in functionally impaired older adults with normal cognition, suggesting that CACE-Is may positively influence activities of daily living (ADL) in dementia.


OBJECTIVE
To compare rates of decline in patients with mild to moderate Alzheimer's disease (AD) receiving CACE-Is to those not currently treated with CACE-Is (NoCACE-I), included in the Doxycycline and Rifampicin for Alzheimer's Disease study (n = 406).


METHODS
Patients were included if baseline and end-point (twelve months apart) scores were available for measures including the Standardized Alzheimer's Disease Assessment Scale - Cognitive Subscale; Quick Mild Cognitive Impairment screen; Clinical Dementia Rating Scale (CDR-SB), and Lawton-Brody ADL Scale.


RESULTS
There was a significant, 25% difference (median one-point) in the 12-month rate of decline in ADL scores in patients taking CACE-Is (n = 91), compared to the NoCACE-I group (n = 274), p = 0.024. This remained significant after adjusting for age, gender, education, and blood pressure, p = 0.034. When individual CACE-Is were compared to the NoCACE-I group, a significant reduction in the rate of decline in ADLs (median one versus four points), were only observed for perindopril, p = 0.01. The CDR-SB was also reduced (median one-point) for the perindopril compared to the NoCACE-I group, p = 0.04.


CONCLUSIONS
This observational study suggests that CACE-Is, and potentially perindopril in particular, are associated with a reduced rate of functional decline in patients with AD, without an association with mood or behavior. This suggests that CACE-Is may slow disease progression in AD.
Centre for Gerontology and Rehabilitation, University College Cork, St Finbarrs Hospital, Cork, Ireland.
Rónán
R
O'Caoimh
Centre for Gerontology and Rehabilitation, University College Cork, St Finbarrs Hospital, Cork, Ireland.
Liam
L
Healy
Centre for Gerontology and Rehabilitation, University College Cork, St Finbarrs Hospital, Cork, Ireland.
Yang
Y
Gao
Department of Clinical Epidemiology & Biostatistics, McMaster University, ON, Canada.
Anton
A
Svendrovski
Department of Pharmacology and Therapeutics, University College Cork, Cork, Ireland Mercy University Hospital, Cork, Ireland.
David M
DM
Kerins
Clinical Research Facility, Mercy University Hospital, Cork, Ireland.
Joseph
J
Eustace
Dementia Research Group, School of Clinical Sciences, University of Bristol, Frenchay Hospital, Bristol, UK.
Patrick Gavin
PG
Kehoe
Department of Clinical Epidemiology & Biostatistics, McMaster University, ON, Canada.
Gordon
G
Guyatt
Centre for Gerontology and Rehabilitation, University College Cork, St Finbarrs Hospital, Cork, Ireland.
D William
DW
Molloy
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications / Q000188:drug therapy*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology; D004311:Double-Blind Method; D004318:Doxycycline / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D017063:Outcome Assessment, Health Care; D011569:Psychiatric Status Rating Scales; D012189:Retrospective Studies; D012293:Rifampin / Q000627:therapeutic use*
D000806:Angiotensin-Converting Enzyme Inhibitors; D004318:Doxycycline; D012293:Rifampin
ACE inhibitors; Alzheimer's disease; cognitive; dementia; function; psychological decline