title: Effects of dronabinol on anorexia and disturbed behavior in patients with Alzheimer's disease. Delta-9-tetrahydrocannabinol for nighttime agitation in severe dementia Psychiatric symptoms and nursing home placement of patients with Alzheimer's disease. Observed affect in nursing home residents with Alzheimer's disease. Donepezil for the treatment of agitation in Alzheimer's disease. Bias in treatment assignment in controlled clinical trials.
abstract: A placebo-controlled crossover design , with each treatment period lasting 6 weeks , was used to investigate effects of dronabinol in 15 patients with a diagnosis of probable Alzhemer 's disease who were refusing food . Eleven patients completed both study periods ; one patient who died of a heart attack 2 weeks before the end of the study was also included in the analysis . The study was terminated in 3 patients : one developed a gr and mal seizure and 2 developed serious intercurrent infections . Body weight of study subjects increased more during the dronabinol treatment than during the placebo periods . Dronabinol treatment decreased severity of disturbed behavior and this effect persisted during the placebo period in patients who received dronabinol first . Adverse reactions observed more commonly during the dronabinol treatment than during placebo periods included euphoria , somnolence and tiredness , but did not require discontinuation of therapy . These results indicate that dronabinol is a promising novel therapeutic agent which may be useful not only for treatment of anorexia but also to improve disturbed behavior in patients with Alzheimer 's disease Rationale Nighttime agitation occurs frequently in patients with dementia and represents the number one burden on caregivers today . Current treatment options are few and limited due to substantial side effects . Objectives The aim of the study was to measure the effect of the cannabinoid dronabinol on nocturnal motor activity . Methods In an open-label pilot study , six consecutive patients in the late stages of dementia and suffering from circadian and behavioral disturbances — five patients with Alzheimer ’s disease and one patient with vascular dementia — were treated with 2.5 mg dronabinol daily for 2 weeks . Motor activity was measured objective ly using actigraphy . Results Compared to baseline , dronabinol led to a reduction in nocturnal motor activity ( P=0.028 ) . These findings were corroborated by improvements in Neuropsychiatric Inventory total score ( P=0.027 ) as well as in subscores for agitation , aberrant motor , and nighttime behaviors ( P<0.05 ) . No side effects were observed . Conclusions The study suggests that dronabinol was able to reduce nocturnal motor activity and agitation in severely demented patients . Thus , it appears that dronabinol may be a safe new treatment option for behavioral and circadian disturbances in dementia Two hundred ten community-dwelling patients with Alzheimer 's disease were examined prospect ively by psychiatrists as part of a longitudinal study . Twenty-five of these patients who were institutionalized during the next 3 years were then matched to 25 patients who were not institutionalized  , and the groups were compared . The patients who had been institutionalized had higher scores on st and ardized psychiatric rating scales but not on formal neuropsychological tests of cognition . These results suggest that potentially treatable ( noncognitive ) behavioral and psychiatric symptoms are risk factors for institutionalization , and that treating these symptoms might delay or prevent institutionalization of some patients A method for assessing affect states among older people with Alzheimer 's disease was developed for use in a study design ed to evaluate a special care unit for such residents of a nursing home . The 6-item  Philadelphia Geriatric Center Affect Rating Scale was design ed for the use of research and other staff in assessing positive affect ( pleasure , interest , contentment ) and negative affect ( sadness , worry/anxiety , and anger ) by direct observation of facial expression , body movement , and other cues that do not depend on self-report , among 253 demented and 43 nondemented residents . Each affect scale was highly reliable , expressed in estimated portions of a 10-minute observation period when the affect expression occurred . Validity estimates were affirmative in showing discriminant correlations between the positive states and various independent measures of social and other outwardly engaged behavior and between negative states and other measures of depression , anger , anxiety , and withdrawal . Limited support for the two-factor dimensionality of the affect ratings was obtained , although positive and negative affect were correlated , rather than independent . Some hope is offered that the preference and aversions of Alzheimer patients may be better understood by observations of their emotional behaviors and that such methods may lead to a better ability to judge institutional quality BACKGROUND Agitation is a common and distressing symptom in patients with Alzheimer 's disease .  Cholinesterase inhibitors improve cognitive outcomes in such patients , but the benefits of these drugs for behavioral disturbances are unclear . METHODS We r and omly assigned 272 patients with Alzheimer 's disease who had clinical ly significant agitation and no response to a brief psychosocial treatment program to receive 10 mg of donepezil per day ( 128 patients ) or placebo ( 131 patients ) for 12 weeks . The primary outcome was a change in the score on the Cohen-Mansfield Agitation Inventory ( CMAI ) ( on a scale of 29 to 203 , with higher scores indicating more agitation ) at 12 weeks . RESULTS There was no significant difference between the effects of donepezil and those of placebo on the basis of the change in CMAI scores from baseline to 12 weeks ( estimated mean difference in change [ the value for donepezil minus that for placebo ] , -0.06 ; 95 % confidence interval [ CI ] , -4.35 to 4.22 ) . Twenty-two of 108 patients ( 20.4 % ) in the placebo group and 22 of 113 ( 19.5 % ) in the donepezil group had a reduction of 30 % or greater in the CMAI score ( the value for donepezil minus that for placebo , -0.9 percentage point ; 95 % CI , -11.4 to 9.6 ) . There were also no significant differences between the placebo and donepezil groups in scores for the Neuropsychiatric Inventory , the Neuropsychiatric Inventory Caregiver Distress Scale , or the Clinician 's Global Impression of Change . CONCLUSIONS In this 12-week trial , donepezil was not more effective than placebo in treating agitation in patients with Alzheimer 's disease . ( Clinical Trials.gov number , NCT00142324 [ Clinical Trials.gov ] . ) Controlled clinical trials of the treatment of acute myocardial infa rct ion offer a unique opportunity for the study of the potential influence on outcome of bias in treatment assignment . A group of 145 papers was divided into those in which the r and omization process was blinded ( 57 papers ) , those in which it may have been unblinded ( 45 papers ) , and those in which the controls were selected by a nonr and om process ( 43 papers ) . At least one prognostic variable was maldistributed ( P less than 0.05 ) in 14.0 per cent of the blinded-r and omization studies , in 26.7 per cent of the unblinded-r and omization studies , and in 58.1 per cent of the nonr and omized studies . Differences in case-fatality rates between treatment and control groups ( P less than 0.05 ) were found in 8.8 per cent of the blinded-r and omization studies , 24.4 per cent of the unblinded-r and omization studies , and 58.1 per cent of the nonr and omized studies . These data emphasize the importance of keeping those who recruit patients for clinical trials from suspecting which treatment will be assigned to the patient under consideration
target: This review finds no evidence that cannabinoids are effective in the improvement of disturbed behaviour in dementia or in the treatment of other symptoms of dementia .
background: BACKGROUND Following the discovery of an endogenous cannabinoid system and the identification of specific cannabinoid receptors in the central nervous system , much work has been done to investigate the main effects of these compounds .
  There is increasing evidence that the cannabinoid system may regulate neurodegenerative processes such as excessive glutamate production , oxidative stress and neuroinflammation .
  Neurodegeneration is a feature common to the various types of dementia and this has led to interest in whether cannabinoids may be clinical ly useful in the treatment of people with dementia .
  Recent studies have also shown that cannabinoids may have more specific effects in interrupting the pathological process in Alzheimer 's disease .
  OBJECTIVES To determine from available research whether cannabinoids are clinical ly effective in the treatment of dementia .