Do neuroleptic drugs hasten cognitive decline in dementia? Prospective study with necropsy follow up.
OBJECTIVE
To investigate the contribution of neuroleptic drugs to cognitive decline in dementia.


METHODS
Two year prospective, longitudinal study consisting of interviews every four months, with necropsy follow up.


METHODS
Community settings in Oxfordshire.


METHODS
71 subjects with dementia, initially living at home with informant.


METHODS
Cognitive function (score from expanded minimental state examination); behavioural problems (physical aggression, hallucinations, persecutory ideas, and disturbance of diurnal rhythm); and postmortem neuropathological assessment (cortical Lewy body pathology).


RESULTS
The mean (SE) decline in cognitive score in the 16 patients who took neuroleptics was twice that in the patients who did not (20.7 (2.9) v 9.3 (1.3), P = 0.002). An increased rate of decline was also associated with aggression, disturbed diurnal rhythm, and persecutory ideas. However, only use of neuroleptics and severity of persecutory ideas were independently associated with more rapid cognitive decline when all other variables were adjusted for. The start of neuroleptic treatment coincided with more rapid cognitive decline: median rate of decline was 5 (interquartile range 8.5) points per year before treatment and 11 (12) points per year after treatment (P = 0.02). Cortical Lewy body pathology did not account for association between neuroleptic use and more rapid decline.


CONCLUSIONS
Neuroleptic drugs that are sometimes used to treat behavioural complications of dementia may worsen already poor cognitive function. Randomised controlled trials are needed to confirm a causal relation.
McShane
R
R
Department of Psychiatry, Warneford Hospital, Oxford.
Keene
J
J
Gedling
K
K
Fairburn
C
C
Jacoby
R
R
Hope
T
T
D000368:Aged; D014150:Antipsychotic Agents / Q000009:adverse effects*; D001344:Autopsy; D003072:Cognition Disorders / Q000139:chemically induced* / Q000473:pathology; D003704:Dementia / Q000150:complications* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D010302:Parkinson Disease, Secondary / Q000473:pathology; D011446:Prospective Studies; D012044:Regression Analysis
D014150:Antipsychotic Agents