Sleep duration during the 24-hour day is associated with the severity of dementia in nursing home patients

STUDY OBJECTIVES: To describe the characteristics of 24-h sleep patterns in nursing home patients with dementia, and to determine whether various degrees of dementia have any influence on total sleep duration. DESIGN AND SETTING: Cross-sectional study in a nursing home population (n = 23) consisting of patients with varying degree of dementia. Sleep was measured with actigraphy for a consecutive period of 14 days, based on individual bed and rising time, which was registered by nursing home staff. MEASUREMENTS AND RESULTS: Mean age +/- standard deviation was 86.1 +/- 7.0 (range 72-96) and mean Mini-Mental Status Examination Score (MMSE) was 13.4 +/- 5.3 (range 1-21). Ten patients had MMSE < or = 12. Sleep was extremely fragmented, with frequent wake bouts during nighttime and frequent naps during daytime. During the 24-h period, patients spent nearly 13 h asleep, distributed as more than 9 h of nighttime sleep and more than 3 h of daytime sleep. Patients with severe degree of dementia (MMSE < or = 12) slept significantly longer during the 24-h day than patients with lesser degree of dementia (MMSE > 12). There was no significant difference in age between the dementia sub-groups. CONCLUSION: Sleep duration during the 24-h day was positively correlated with the severity of dementia in nursing home patients. This is in contrast with total sleep time seen in healthy elderly, which shows a gradually decline with age. Changes in sleep patterns in dementia could be explained by co-morbid and environmental factors, as well as unknown pathological changes related to dementing illnesses.     

Lavender oil as a treatment for agitated behaviour in severe dementia: a placebo controlled study

OBJECTIVE: To determine whether aromatherapy with lavender oil is effective in the treatment of agitated behaviour in patients with severe dementia. DESIGN: A placebo controlled trial with blinded observer rater. SETTING: A long-stay psychogeriatric ward. PATIENTS: Fifteen patients meeting ICD-10 diagnostic criteria for severe dementia and suffering from agitated behaviour defined as a minimum score of three points on the Pittsburgh Agitation Scale (PAS). INTERVENTION: A 2% lavender oil aromatherapy stream was administered on the ward for a two hour period alternated with placebo (water) every other day for a total of ten treatment sessions. ASSESSMENTS: For each subject 10 total PAS scores were obtained. Five during treatment and five during placebo periods. RESULTS: Nine patients (60%) showed an improvement, five (33%) showed no change and one patient (7%) showed a worsening of agitated behaviour during aromatherapy compared with placebo. A comparison of the group median PAS scores during aromatherapy showed a significant improvement in agitated behaviour during aromatherapy compared with placebo (median PAS scores 3 c.f. 4; Wilcoxon Signed-Ranks test p = 0.016 (one-tailed)). CONCLUSIONS: Lavender oil administered in an aroma stream shows modest efficacy in the treatment of agitated behaviour in patients with severe dementia.     

A comparison of the Cohen-Mansfield agitation inventory with the cerad behavioral rating scale for dementia in community-dwelling persons with Alzheimers disease

In a group of 242 community-dwelling patients with Alzheimers disease (AD), a longitudinal comparison was made of two caregiver-administered instruments for assessment of behavioral disturbance; the Cohen-Mansfield Agitation Inventory (CMAI) and the CERAD Behavioral Rating Scale for Dementia (BRSD). We examined records of the 206 patients with baseline and 12-month follow-up data for the CMAI and the BRSD who also had tests of cognitive (Mini-mental State; MMSE) and global function (Clinical Dementia Rating; CDR and Functional Assessment Staging; FAST). Among 114 AD subjects, the correlation between total CMAI at baseline and 1 month readministration was 0.83 (p<0.0001). In the same subjects, stratified into 5 groups by MMSE scores, the correlations between BRSD baseline and 1-month scores ranged from 0.70–0.89 (p<0.0001). There was high correlation between total scores of both instruments at baseline and 12 months. In addition, all CMAI subscales except Verbally Aggressive correlated significantly with total BRSD score at both time points. At baseline, BRSD subscales for irritability\aggression, behavioral dysregulation and psychotic symptoms and at 12 months, irritability\aggression and behavioral dysregulation correlated with total CMAI scores. Neither scale changed significantly over 1 year, but there was wide individual variation. CMAI and BRSD scores correlated with 1-year change in the FAST, but not with MMSE or CDR (which weighs cognition heavily), suggesting that behavioral disturbance may be more strongly related to ability to manage activities of daily living (executive function) than to other aspects of cognition. The CMAI and BRSD appear to be interchangeable as measures of agitation, with the CMAI possibly more useful for patients who lack language and the BRSD more sensitive to apathy and depression.     

Quetiapine to treat agitation in dementia: a randomized, double-blind, placebo-controlled study

In this 10-week, double-blind, fixed-dose study, elderly institutionalized patients with dementia and agitation were randomized (3:3:2) to quetiapine 200mg/day, 100mg/day, or placebo. The primary endpoint was change in Positive and Negative Syndrome Scale (PANSS)-Excitement Component (EC) scores at endpoint, analysed using last observation carried forward (LOCF) and observed cases (OC) approaches. Other efficacy measures were the Clinical Global Impression of Change (CGI-C), and response rates (percentage with > or =40% reduction [PANSS-EC]; "much" or "very much improved" [CGI-C]), Neuropsychiatric Inventory-Nursing Home version (NPI-NH), and Cohen-Mansfield Agitation Inventory (CMAI). The key safety measure was incidence of adverse events; change in Mini-Mental State Examination (MMSE) was also assessed. Baseline characteristics of 333 participants (quetiapine 200mg/day, n=117; quetiapine 100mg/day, n=124; placebo, n=92) and completion rates (63-65%) were comparable among groups. Compared with placebo, quetiapine 200mg/day was associated with clinically greater improvements in PANSS-EC (LOCF, p=0.065; OC, p=0.014 [ANCOVA]), CGI-C (LOCF, p=0.017; OC, p=0.002 [ANOVA]), and CGI-C response rates (LOCF, p=0.002; OC, p<0.001 [Chi-square test]). Quetiapine 100mg/day did not differentiate from placebo on these measures. There were no between-group differences in NPI-NH or CMAI. Incidences of cerebrovascular adverse events, postural hypotension, and falls were similar among groups. MMSE did not change in any group. Mortality was numerically higher in the quetiapine groups; rates were not statistically different from placebo. The results of this study suggest that quetiapine 200mg/day was effective and well-tolerated for treating agitation associated with dementia. However, caution should be exercised given the concerns regarding increased mortality with atypical antipsychotics in this vulnerable patient population.     

Quetiapine versus risperidone in elderly patients with behavioural and psychological symptoms of dementia: efficacy, safety and cognitive function.

OBJECTIVE: In this study we directly compared the efficacy and tolerability of the atypical antipsychotics quetiapine and risperidone in elderly patients with dementia and symptoms of disturbed perception, thought content, mood or behaviour (behavioural and psychological symptoms of dementia-BPSD). METHODS: We conducted an 8-week, rater-blinded, randomised study of 72 outpatients (55-85 years) with BPSD (assessed by NPI baseline score), who received flexibly-dosed quetiapine (50-400 mg/day) or risperidone (0.5-2 mg/day). Primary efficacy measure: Neuropsychiatric Inventory (NPI) Parts 1 and 2; secondary efficacy measures: Clinical Global Impression (CGI), Cohen-Mansfield Agitation Inventory (CMAI), Mini-Mental State Examination (MMSE), Age-adjusted concentration test (AKT). Safety evaluations included the incidence of extrapyramidal symptoms (EPS) and adverse events (AEs). RESULTS: Sixty-nine of 72 patients were evaluable for efficacy (72 were evaluated for safety), 4 patients discontinued (3 due to AEs: quetiapine 2, risperidone 1; 1 lost to follow-up). Sixty-five patients received quetiapine (n=34; mean dose 77+/-40 mg/day) or risperidone (n=31; mean dose 0.9+/-0.3 mg/day). There was no significant difference between treatments on NPI scores; within treatment groups, NPI scores decreased significantly from baseline to Week 8 (P相似文献   

Validity and responsiveness to change of clinically derived MDS scales in Alzheimer disease outcomes research

This analysis assessed 3 subscales derived from the nursing home Minimum Data Set (MDS), the Cognitive Performance Scale (CPS), Depression Rating Scale (DRS), and Aggressive Behavior Scale (ABS), as outcome measures in clinical trials of long-term care residents with Alzheimer disease (AD). A total of 26 patients with moderate-to-severe AD and agitation/aggression enrolled in a trial of memantine were assessed using the Mini-Mental State Examination (MMSE), Neuropsychiatric Inventory Nursing Home Version (NPI-NH), and the Cohen-Mansfield Agitation Inventory (CMAI) administered by trained researchers. MDS data were collected as part of their standard clinical care. The MDS subscales correlated significantly with their corresponding research scales: CPS and MMSE (r = -0.57, P = .003); DRS and NPI-NH total (r = 0.42, P = .038); DRS and NPI-NH depression (r = 0.41, P = .04), and ABS and CMAI (r = 0.54, P = .004). DRS and ABS scores did not change significantly from baseline to 3 months though the NPI-NH and CMAI did, indicating limited sensitivity to change. This suggests that the MDS subscales measure comparable aspects of cognitive function and depressive and agitated/aggressive behavior as the MMSE, NPI-NH, and CMAI. However, this analysis also suggests that sensitivity to change of the DRS and ABS may be limited compared to the NPI-NH and CMAI. As these findings are preliminary, further research is needed to determine the utility of MDS scales in outcomes research.     

Reliability and validity of the Japanese version of the Agitated Behaviour in Dementia Scale in Alzheimer's disease: three dimensions of agitated behaviour in dementia

Background: Agitation in dementia seriously affects not only patients' quality of life (QOL), but also caregivers' QOL. Thus, an appropriate assessment of agitated behaviour in dementia is needed for clinical management. We developed the Japanese version of the Agitated Behaviour in Dementia scale (ABID), examined its reliability and validity, and carried out its factor analysis to elucidate its factor structure. Methods: The Japanese version of the ABID was given caregivers of 149 Japanese patients with Alzheimer's disease (AD). The internal‐consistency, test–retest reliability and concurrent validity of the Japanese version of the ABID were then examined. A factor analysis was used to examine the agitated behavioural dimensions underlying ABID. Results: The Japanese version of the ABID showed an excellent internal reliability for both frequency ratings (Cronbach's α= 0.89) and reaction ratings (Cronbach's α= 0.92), and an excellent test–retest reliability for both frequency ratings and reaction ratings. The total score for the frequency ratings of the ABID was significantly associated with the Cohen‐Mansfield Agitation Inventory (CMAI), and the total score for the reaction ratings of the ABID was significantly associated with the Zarit Burden Interview. The factor analysis showed three subtypes: physically agitated behaviour, verbally agitated behaviour and psychosis symptoms. Conclusions: The Japanese version of the ABID promises to be useful for assessing agitated behaviour in patients with AD. Importantly, understanding these subtypes of agitated behaviour might have implications for individualized treatment plans.     

Wrist actigraphy in estimation of sleep and wake in intellectually disabled subjects with motor handicaps

BACKGROUND AND PURPOSE: We studied the applicability of wrist actigraphy to sleep-wake estimation in patients with motor handicaps. PATIENTS AND METHODS: Concomitant polysomnographic and actigraphic recordings (16-24 h) were compared in three groups: normally moving subjects with normal sleep (n=10), sleep-disordered subjects without motor handicaps (n=13) and sleep-disordered patients with different motor disabilities (n=16). The motor abilities of the subjects were determined by clinical evaluation using a grading scale from 0 to 10. Their actual daily activity was calculated from the recordings as average activity scores. RESULTS: In the healthy subjects, the mean difference between actigraphic and polysomnographic total sleep estimation was negligible (-1 min), while in both sleep-disordered groups, sleep was highly overestimated by actigraphy. There was a significant correlation between the motor ability score and the discrepancy between actigraphy and polysomnography, but individual data points were highly scattered. A more consistent correlation was found between the average activity score/min in actigrams and the discrepancy of actigraphic with polysomnographic total sleep estimation (Spearman's r=-0.58, P=0.0001, n=39). When the recordings with very low average activity score were rejected from the analyses (two patients without and six with motor handicaps), the overestimation of sleep by actigraphy was reduced but it still remained in both sleep-disordered groups. The mean differences of total sleep between actigraphy and polysomnography were 72 and 121 min and the rank order correlation coefficients 0.80 and 0.71 in patients without and with motor handicaps, respectively. The median discrepancy in total sleep estimation was 6% in both sleep-disordered groups. CONCLUSIONS: In subjects with rudimentary motor abilities, a standard actigraphy can produce a signal, which is related to the amount of sleep scored in polysomnograms. The sleep parameters obtained by the two methods are not equal, however. The inspection of actigrams is more reliable than the clinical scaling of motor abilities in predicting the applicability of wrist actigraphy.     

De novo genesis of neuropsychiatric symptoms in mild cognitive impairment (MCI)

BACKGROUND: There is inadequate information regarding the neuropsychiatric aspect of Mild Cognitive Impairment (MCI). OBJECTIVE: To determine the neuropsychiatric profile of MCI, and compare this with normal controls and patients with mild Alzheimer's Disease (AD). DESIGN: Cross-sectional assessment of psychiatric symptoms in subjects that are enrolled in Mayo Clinic's longitudinal study of normal aging, MCI and dementia. METHODS AND PARTICIPANTS: The Neuropsychiatric Inventory (NPI) was administered to normal control subjects, MCI subjects and patients with early AD. Individual NPI domain scores and total NPI scores were compared among the three groups after controlling for age, educational status, Dementia Rating Scale (DRS) and Mini-Mental State Examination (MMSE) scores. Statistical analysis was performed by utilizing ANOVA, chi2 and Fisher's exact test. RESULTS: Data were analyzed on 514 normal controls, 54 MCI subjects, and 87 subjects with mild AD (CDR of 0.5 or 1); females consisted of 60.3%, 53.7% and 57.5%; and, the average ages (SD) were 77.8 (1.95), 79 (4.6), 80.5 (14.6) respectively. ANOVA pair-wise comparison revealed that both MMSE and DRS differences among the three groups were significantly different at (p = 0.05). The total NPI scores were significantly different (p =0.0001, F = 107.93) among the three groups using ANOVA. Pair-wise comparison of individual behavioral domain of NPI showed statistically significant differences between MCI and normals; and MCI and AD (p = 0.001). Group differences on NPI remained after controlling for age and education at p = 0.0375 and p = 0.0050 respectively. CONCLUSION: The neuropsychiatric pattern is reminiscent of the clinical, neuroimaging and neuropsychological profile of MCI. It gives further credence to the view that MCI is indeed the gray zone, with overlap on both ends of the pole.     

A comparison of polysomnographic and actigraphic evaluation of periodic limb movements in sleep

OBJECTIVE: As a standard method, periodic limb movements in sleep (PLMS) are detected by means of polysomnography (PSG). Actigraphic detection of PLMS is a recently developed method for performing of multiple-night recordings in an outpatient setting. The aim of our study was to assess sensitivity-related parameters of actigraphic detection of PLMS in comparison to the PSG, when mounted at ankles and at the base of the big toe. METHODS: We simultaneously performed PSG and actigraphic recordings at both ankles and at the bases of both big toes (Cambridge Actiwatch AW-64) for 40 nights. The PLM index (PLMI), number of periodic movements per hour of sleep, was the primary output of both methods. RESULTS: We have proven significant correlation of all resulting parameters when comparing actigraphy at either position to the PSG; however, the PLMI values obtained by the actigraphy at toes were significantly higher than by PSG (sign test, p<0.0001). At bases of the big toes, threshold of PLMI=7.6 was used as a cut off for positivity, while PLMI=5 at ankles was used for PSG. Comparing ankle versus toe actigraphic placement, sensitivity was 67% versus 94%, specificity was 95% versus 91% and negative predictive value was 78% versus 95%. The correlation of the results from actigraphy and PSG was not affected by presence of respiratory events. DISCUSSION: Our results suggest good validity of actigraphic PLM evaluation at the base of big toe using AW-64 devices and therefore, actigraphy seems suitable for screening purposes in both clinical and research usage.     

Components of behavioral pathology in dementia

OBJECTIVE: The purpose of this study was to examine the occurence of the noncognitive behavioral and psychological symptoms and signs of dementia in a geriatric chronic-care hospital and to separate agitated and affective components of behavioral pathology using factor analysis. METHODS: The frequency and severity of Alzheimer's disease, vascular dementia, mixed dementia and Lewy Body dementia was assessed in 145 consecutive residents of a chronic-care hospital. The presence of noncognitive behavioral symptoms was evaluated with the Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD) and the Cohen-Mansfield Agitation Inventory (CMAI). A Factor analysis on the BEHAVE-AD subscores was performed to create symptom clusters. Analysis of covariance and post hoc tests were used to compare means of factor variables between different types of dementia. RESULTS: Statistical analysis showed a significant correlation between severity of dementia and BEHAVE-AD total score and between severity of dementia and CMAI total score. Factor analysis with Varimax rotation revealed the presence of three behavioral subsyndromes: agitation, affectivity and day/night disturbances. CONCLUSIONS: The finding of three factors of behavioral pathology in demented patients reflects the possibility that different etiological mechanisms could explain the expression of the symptoms and signs of psychosis in demented patients.     

Sleep in Parkinson's disease: A comparison of actigraphy and subjective measures

Sleep disturbances are common in Parkinson's disease (PD). Actigraphy has emerged as an alternative to polysomnography to measure sleep, raising the question of its ability to capture sleep quality in PD patients. Our aim was to compare self-report data with actigraphic data. Thirty non-demented individuals with PD and 14 normal control participants (NC) were included. Sleep was measured using 24-h wrist actigraphy over a seven day period, during which time participants kept a sleep diary. Subjective sleep and arousal questionnaires included the Parkinson's Disease Sleep Scale and Epworth Sleepiness Scale. Patients with PD presented with more sleep problems than NC. In NC, none of the actigraphic sleep variables were related to any of the self-report measures of sleep. In PD, scores on subjective sleep measures correlated with actigraphy-derived estimates of sleep quality. Our results suggest that actigraphy is an appropriate method of measuring sleep quality in PD.     

The clinical applications of Mini-Mental State Examination in geropsychiatric inpatients

OBJECTIVE: This study investigated the association between Mini-Mental State Examination (MMSE) scores and diagnosis, computerized tomographic scans or electroencephalogram findings in geropsychiatric inpatients (age > or = 65). METHOD: We analyzed the MMSE records of patients sixty-five and older who had been hospitalized in our psychiatric ward during a nine-year period. Case data were collected by review of chart records. RESULTS: In these patients, MMSE scores were significantly different among the seven diagnostic groups included. Demented patients had the lowest MMSE scores. Patients who had abnormal findings on computerized tomographic scans or electroencephalogram had lower MMSE than patients with normal findings. CONCLUSION: Our findings suggest that the MMSE is a useful screening instrument for organicity in the geropsychiatric inpatients. However, because of the lower average MMSE score in geropsychiatric inpatients, the optimal cut-offpoint of MMSE for dementia should be lower than those used in other populations.     

Education effects on cognitive function in a healthy aged Arab population

BACKGROUND: The Mini-mental State Examination (MMSE) has not been validated in Arabic speaking populations. The Brookdale Cognitive Screening Test (BCST) has been developed for use in low schooling populations. We investigated the influence of gender, education and occupation in a cognitively normal community sample which was assessed using an Arabic translation of the MMSE and the BCST. METHODS: Cognitively normal subjects (n=266, 59.4% males, mean age (SD): 72.4 (5.5) years) from an Arab community in northern Israel (Wadi Ara) were evaluated. Education was categorized into levels: 1=0-4 years, 2=5-8 years, 3=9-12 years. Effects of gender, education and occupation on MMSE and BCST were analyzed by ANOVA, taking age as a covariate. RESULTS: The mean MMSE score of males [26.3 (4.1)] was higher than that of females [23.6 (4.2) points]. Two-way ANOVA showed a significant interaction between gender and education on MMSE (p=0.0017) and BCST scores (p=0.0002). The effect of gender on MMSE and BCST was significant in education level 1 (p<0.0001, both tests) and level 2 (p<0.05, both tests). For education level 1, MMSE and BCST scores were higher for males, while both scores were higher for females in education level 2. The effect of occupation was not significant for both genders. CONCLUSION: Education and gender influence performance when using the Arabic translation of the MMSE and BCST in cognitively normal elderly. Cognitively normal females with 0-4 years of education scored lower than males. These results should be taken into consideration in the daily use of these instruments in Arabic.     

Actigraphic daytime activity is reduced in patients with cognitive impairment and apathy

ObjectivesApathy is a neuropsychiatric symptom in mild cognitive impairment (MCI) and dementia. This study examines correlations between Apathy Evaluation Scale (AES) ratings and actigraphic measures of daytime activity. The aim of this study is to determine the value of ambulatory actigraphy in the assessment of locomotor deficits as a correlate of apathy in geriatric patients with cognitive impairment.Patients and methodsIn this cross-sectional study a total of 82 participants were recruited, 32 patients with dementia, 21 patients with MCI and 23 elderly controls. Rating scales for apathy (AES) and depression (Beck Depression Inventory, BDI) were completed. To measure daytime activity a wrist-worn actigraph and an established protocol were used. A single measure of mean daytime activity per participant was calculated for further statistical analysis.ResultsIn the two groups of patients with MCI and dementia, apathy is associated with reduced daytime activity, independent of diagnosis (no group by apathy interaction). AES scores correlate significantly with daytime activity. Cognitive impairment reduces daytime activity (effect greater in dementia than in MCI). Daytime activity is negatively correlated with memory deficits.ConclusionAmbulatory actigraphy is a promising method to evaluate self-initiated action as a correlate of apathy in patients with cognitive impairment.     

Aripiprazole for the treatment of psychoses in institutionalized patients with Alzheimer dementia: a multicenter, randomized, double-blind, placebo-controlled assessment of three fixed doses.

OBJECTIVE: To assess the efficacy and safety of aripiprazole for psychosis associated with Alzheimer dementia (AD). METHODS: In this double-blind, multicenter study, 487 institutionalized patients with psychosis associated with AD were randomized to placebo or aripiprazole, 2, 5 or 10 mg/day. Primary efficacy assessment was the mean change from baseline to week 10 on the Neuropsychiatric Inventory-Nursing Home (NPI-NH) version Psychosis Subscale score. Secondary measures included NPI-NH Total, Clinical Global Impression-Severity of Illness (CGI-S), Brief Psychiatric Rating Scale (BPRS) Core and Total, and the Cohen-Mansfield Agitation Inventory (CMAI) scores. RESULTS: Aripiprazole 10 mg/day showed significantly greater improvements (mean change [2 x SD]) than placebo on the NPI-NH Psychosis Subscale (-6.87 [8.6] versus -5.13 [10.0]; F = 6.29, df = 1, 422, p = 0.013 by analysis of covariance [ANCOVA]); CGI-S (-0.72 [1.8] versus -0.46 [1.6]; F = 4.68, df = 1, 419, p = 0.031 [ANCOVA]); BPRS Total (-7.12 [18.4] versus -4.17 [21.6]; F = 4.72, df = 1, 399, p = 0.030 [ANCOVA]); BPRS Core (-3.07 [6.9] versus -1.74 [7.8]; F = 7.30, df = 1, 407, p = 0.007 [ANCOVA]); CMAI (-10.96 [22.6] versus -6.64 [28.6]; F = 5.23, df = 1, 410, p = 0.023 [ANCOVA]), and NPI-NH Psychosis response rate (65 versus 50%; chi(2) = 5.52, df = 1, p = 0.019 [CMH]). Aripiprazole 5 mg/day showed significant improvements versus placebo on BPRS and CMAI scores. Aripiprazole 2 mg/day was not efficacious. Cerebrovascular adverse events were reported: aripiprazole 2 mg/day, N = 1; 5 mg/day, N = 2; 10 mg/day, N = 4; placebo, N = 0. No deaths in any group (aripiprazole 2 mg/day, 3%; 5 mg/day, 2%; 10 mg/day, 7%; placebo, 3%) were considered to be treatment-related. CONCLUSION: Aripiprazole 10 mg/day was efficacious and safe for psychosis associated with AD, significantly improving psychotic symptoms, agitation, and clinical global impression. However, clinicians should be aware of the safety considerations of atypical antipsychotic uses in this population.     

The relationship between homocysteine, cognition and stroke subtypes in acute stroke

BACKGROUND: Elevations in plasma homocysteine (Hcy) have been associated with an increased risk of stroke and dementia. The mechanisms underlying these associations remain poorly understood. OBJECTIVES: This study examines the relationships between Hcy, cognition, and stroke subtype. We hypothesize that: 1) Hcy levels are inversely related to cognition, 2) Hcy levels are unrelated to stroke subtype, and 3) stroke subtype affects cognition. METHODS: We studied 169 consenting patients admitted for acute stroke during a 4 month period. Blood was drawn for Hcy levels and the Mini-Mental State Examination (MMSE) was administered within 9 days of admission. The Oxfordshire Community Stroke Project Classification was used to characterize stroke subtypes. Correlation between Hcy and MMSE scores was examined as was the relationships between Hcy and stroke subtype, and between stroke subtypes and MMSE scores. RESULTS: A significant inverse correlation between Hcy levels and MMSE scores was demonstrated (r=-0.243, p=0.001). MMSE scores also differed according to the type of stroke, with Total or Partial Anterior Circulation Infarcts (TACI/PACI) scoring lowest (F=8.77, df=2, p<0.001). Hcy levels did not differ between the various stroke subtypes (F=0.21, df=2, p=0.81). Multivariate linear regression analysis showed that age, education, and stroke subtype, but not Hcy, were independent predictors of acute MMSE scores. CONCLUSIONS: In this study sample, there was an inverse relationship between Hcy and cognition in acute stroke patients. However, Hcy was not an independent predictor for cognition in acute stroke after other factors such as stroke subtype and patient age were taken into account. These results suggest that during the acute stage of stroke, stroke subtype is a more important factor in determining cognition than Hcy levels.     

Opioid treatment for agitation in patients with advanced dementia

BACKGROUND: Some patients with advanced dementia cannot convey the experience of pain verbally and may react to pain with aggressive and agitated behaviors. We hypothesized that unrecognized pain could contribute to agitation and that low dose opioid therapy might reduce agitation by reducing pain. We therefore attempted to determine the effect of opioids on agitation in demented patients. METHODS: We administered placebo for 4 weeks and a long-acting opioid for another 4 weeks to nursing home patients with advanced dementia and severe agitation despite treatment with psychotropic drugs. Patients and study nurses did not know if the medication administered was placebo or opioid. We measured the Cohen-Mansfield Agitation Inventory (CMAI) score at baseline and every two weeks. RESULTS: Among 47 patients who entered the study, 25 completed the two phases. The median age for the 25 patients was 85.5 years. Analyses of the data of these 25 patients and of the patients <85 years-old showed no significant differences in agitation level between the placebo and opioid phases. However, among the 13 patients who completed the study and were > or =85 years old, the agitation level at the end of the opioid phase was significantly lower than at the end of the placebo phase (mean change in CMAI score: -6.4; 95% confidence interval (CI): -10.96, -1.8). The decrease in agitation in the patients > or =85 years old persisted after adjusting for sedation. The results remained unchanged when we expanded the analyses to include four > or =85 patients who dropped out of the study after the second week of the opioid phase. CONCLUSION: Low dose, long-acting opioids can lessen agitation that is difficult to control in very old (> or =85) patients with advanced dementia.     

A randomized placebo-controlled trial of risperidone for the treatment of aggression,agitation, and psychosis of dementia

BACKGROUND: This randomized, double-blind, placebo-controlled trial examined the efficacy and safety of risperidone in the treatment of aggression, agitation, and psychosis in elderly nursing-home patients with dementia. METHOD: Elderly patients with a DSM-IV diagnosis of dementia of the Alzheimer's type, vascular dementia, or a combination of the 2 (i.e., mixed dementia) and significant aggressive behaviors were randomized to receive, for a period of 12 weeks, a flexible dose of either placebo or risperidone solution up to a maximum of 2 mg/day. Outcome measures were the Cohen-Mansfield Agitation Inventory (CMAI), the Behavioral Pathology in Alzheimer's Disease (BEHAVE-AD) rating scale, and the Clinical Global Impression of Severity (CGI-S) and of Change (CGI-C) scales. RESULTS: A total of 345 patients were randomized to treatment with risperidone or placebo, and 337 patients received at least one dose of study drug. The trial was completed by 67% of patients in the placebo group and 73% of patients in the risperidone group. The mean +/- SE dose of risperidone was 0.95 +/- 0.03 mg/day. The primary endpoint of the study, the difference from baseline to endpoint in CMAI total aggression score, showed a significant reduction in aggressive behavior for risperidone versus placebo (p <.001). A similar improvement was also seen for the CMAI total non-aggression subscale (p <.002) and for the BEHAVE-AD total (p <.001) and psychotic symptoms subscale (p =.004). At endpoint, the CGI-S and the CGI-C scores indicated a significantly greater improvement with risperidone compared with placebo (p <.001). Overall, 94% and 92% of the risperidone and placebo groups, respectively, reported at least 1 adverse event. Somnolence and urinary tract infection were more common with risperidone treatment, whereas agitation was more common with placebo. There was no significant difference in the number of patients who reported extrapyramidal symptoms between the risperidone (23%) and placebo (16%) groups. CONCLUSION: Treatment with low-dose (mean = 0.95 mg/day) risperidone resulted in significant improvement in aggression, agitation, and psychosis associated with dementia.