{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T19:29:43Z","timestamp":1778959783781,"version":"3.51.4"},"reference-count":43,"publisher":"BMJ","issue":"7076","license":[{"start":{"date-parts":[[1997,1,25]],"date-time":"1997-01-25T00:00:00Z","timestamp":854150400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.bmj.com\/company\/legal-information\/terms-conditions\/legal-information\/tdm-licencepolicy"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["BMJ"],"accepted":{"date-parts":[[1996,10,31]]},"published-print":{"date-parts":[[1997,1,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:bold>Objective:<\/jats:bold>\n                    To investigate the contribution of neuroleptic drugs to cognitive decline in dementia.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Design:<\/jats:bold>\n                    Two year prospective, longitudinal study consisting of interviews every four months, with necropsy follow up.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Setting:<\/jats:bold>\n                    Community settings in Oxfordshire.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Subjects:<\/jats:bold>\n                    71 subjects with dementia, initially living at home with informant.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Main outcome measures:<\/jats:bold>\n                    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).\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    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)\n                    <jats:italic>v<\/jats:italic>\n                    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.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusions:<\/jats:bold>\n                    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.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:boxed-text position=\"float\">\n                      <jats:sec>\n                        <jats:title>Key messages<\/jats:title>\n                        <jats:list list-type=\"bullet\">\n                          <jats:list-item>\n                            <jats:p>Neuroleptic drugs are used to treat behavioural problems in patients with dementia, but they may cause more rapid decline in cognitive function<\/jats:p>\n                          <\/jats:list-item>\n                          <jats:list-item>\n                            <jats:p>In our longitudinal study of patients with dementia we found that the rate of cognitive decline in patients taking neuroleptics was twice that in those not taking neuroleptics<\/jats:p>\n                          <\/jats:list-item>\n                          <jats:list-item>\n                            <jats:p>Furthermore, the start of neuroleptic treatment was associated with an increase in the rate of cognitive decline<\/jats:p>\n                          <\/jats:list-item>\n                          <jats:list-item>\n                            <jats:p>Cortical Lewy body pathology at necropsy did not account for the association between neuroleptic use and more rapid decline<\/jats:p>\n                          <\/jats:list-item>\n                          <jats:list-item>\n                            <jats:p>Although our study does not prove a causal relation, we suggest that there should be regular review of the need for patients to continue taking neuroleptic drugs<\/jats:p>\n                          <\/jats:list-item>\n                        <\/jats:list>\n                      <\/jats:sec>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1136\/bmj.314.7076.266","type":"journal-article","created":{"date-parts":[[2011,10,27]],"date-time":"2011-10-27T19:45:02Z","timestamp":1319744702000},"page":"266","source":"Crossref","is-referenced-by-count":188,"title":["Do neuroleptic drugs hasten cognitive decline in dementia? 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Neuropathologic findings after neuroleptic long-term therapy. In: Roizin L, Shiraki H, Grcevic N, eds. Neurotoxicology. New York: Raven Press, 1977: 25\u201342."},{"key":"2025122312540453000_314.7076.266.39","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1176\/ajp.151.10.1430","article-title":"Increase in caudate nuclei volumes of first-episode schizophrenic patients taking antipsychotic drugs.","volume":"151","author":"Chakos","year":"1994","journal-title":"Am J Psychiatry"},{"key":"2025122312540453000_314.7076.266.40","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1177\/089198879100400206","article-title":"Caudate hyperintensities in elderly depressed patients with neuroleptic-induced parkinsonism.","volume":"4","author":"Figiel","year":"1991","journal-title":"J Geriatr Psychiatry Neurol"},{"key":"2025122312540453000_314.7076.266.41","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1097\/00002093-199408040-00001","article-title":"Neurofibrillary pathology in brains of elderly schizophrenics treated with neuroleptics.","volume":"8","author":"Wisniewski","year":"1994","journal-title":"Alzheimer Dis Assoc Disord"},{"key":"2025122312540453000_314.7076.266.42","doi-asserted-by":"crossref","first-page":"1592","DOI":"10.1046\/j.1471-4159.1996.66041592.x","article-title":"Presynaptic serotonergic markers in community-acquired cases of Alzheimer's disease: correlations with depression and neuroleptic medication.","volume":"66","author":"Chen","year":"1996","journal-title":"J Neurochem"},{"key":"2025122312540453000_314.7076.266.43","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1136\/jnnp.61.2.127","article-title":"The basis for behavioural disturbances in dementia.","volume":"61","author":"Esiri","year":"1996","journal-title":"J Neurol Neurosurg Psychiatry"}],"container-title":["BMJ"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/data.bmj.org\/tdm\/10.1136\/bmj.314.7076.266","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmj.314.7076.266","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T20:54:17Z","timestamp":1766523257000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.bmj.com\/lookup\/doi\/10.1136\/bmj.314.7076.266"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1997,1,25]]},"references-count":43,"journal-issue":{"issue":"7076","published-online":{"date-parts":[[1997,1,25]]},"published-print":{"date-parts":[[1997,1,25]]}},"alternative-id":["10.1136\/bmj.314.7076.266"],"URL":"https:\/\/doi.org\/10.1136\/bmj.314.7076.266","relation":{},"ISSN":["0959-8138","1468-5833"],"issn-type":[{"value":"0959-8138","type":"print"},{"value":"1468-5833","type":"electronic"}],"subject":[],"published":{"date-parts":[[1997,1,25]]}}}