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A study was conducted to evaluate whether supplementation with decosahexaenoic acid (DHA) was effective in reducing the cognitive decline in AlzheimerEs disease. Results indicated that DHA supplementation did not have any effect on cognitive decline in such cases.

Background: Factors that affect the rate of progression of Alzheimer disease (AD) need to be considered in the clinical trial designs of potential disease-modifying therapies. Objective: To determine the influence of age on AD course in a clinical trial setting. Design: Pooled cohort study from 3 AD clinical trials of 18-month duration conducted by the Alzheimer Disease Cooperative Study group. Setting: Alzheimer disease research centers from across the United States. Patients: Four hundred seventy-one subjects with mild to moderate AD assigned to the placebo arm of 3 clinical trials. Main Outcome Measures: The relationships between baseline age and rate of change in the Alzheimer Disease Assessment Scale-cognitive subscale (ADAS-cog) 11, Mini-Mental State Examination, Clinical Dementia Rating scale Sum of Boxes score, Alzheimer Disease Cooperative Study-activities of daily living scale, and Neuropsychiatric Inventory were analyzed using a mixed-effect regression model. Sample size calculation for possible future AD clinical trials lasting 18 months using the results of the change in ADAS-cog 11 by tertiles of age groups. Results: Older age at baseline was associated with a slower rate of decline in the ADAS-cog 11 and the Mini-Mental State Examination scores. Almost twice as many subjects aged 80 years and older compared with those aged younger than 70 years would be required to demonstrate a 30% treatment effect on the ADAS-cog 11 in an 18-month AD trial. Conclusion: Subject age is an important factor to consider when defining the study population in and analyzing data from AD trials of potential disease-modifying therapies. [ABSTRACT FROM AUTHOR]

Objective: To estimate the incidence rate and predictors of seizures in patients with mild to moderate Alzheimer disease (AD). Design: Cohort study of patients with mild to moderate AD in clinical trials. Risk factors for potential seizures were evaluated by stratified descriptive statistics and univariable and multivariable Cox proportional hazards regressions. Setting: Pooled patient-level data from 10 Alzheimer Disease Cooperative Study clinical trials in mild to moderate AD from 1995 to 2010. Patients: Three thousand seventy-eight subjects randomized to the treatment or placebo arms of 10 AD clinical trials. Screening Mini-Mental State Examination scores ranged between 10 and 28. Results: Eighteen seizures were reported in 3078 randomized subjects, with an incidence rate of 484 per 100 000 person-years (95% CI, 287-764). Statistically significant independent risk factors for seizure were younger age (adjusted hazard ratio, 0.80; 95% CI, 0.69-0.93 per every 5 years of age), greater cognitive impairment at baseline (adjusted hazard ratio, 2.79; 95% CI, 1.06-7.33 for Mini-Mental State Examination scores <18 compared with Mini-Mental State Examination scores ⩾18), and antipsychotic use at baseline (adjusted hazard ratio, 3.47; 95% CI, 1.33-9.08). Conclusions: Seizure rates in patients with mild to moderate AD in clinical trials are similar to rates observed in longer observational cohort studies, but they are greater than expected in the general elderly population. Younger age, greater degree of cognitive impairment, and history of antipsychotic use were independent risk factors for new on set seizures in AD. [ABSTRACT FROM AUTHOR]

The article focuses on a study which examined the efficacy of valproate therapy in delaying or preventing the emergence of agitation or psychosis. A number of individuals with moderate Alzheimer's disease served as subjects in this study. According to the study, higher rates of somnolence, gait disturbance, tremor, diarrhea and weakness were observed in the valproate group. The study also found greater loss in hippocampal and whole-brain volume in the valproate group.

Objective: To evaluate the safety, tolerability, and amyloid β(Aβ) response to the γ-secretase inhibitor LY450139 in Alzheimer disease. Design: Multicenter, randomized, double-blind, dose escalation, placebo-controlled trial. Setting: Community-based clinical research centers. Patients: Fifty-one individuals with mild to moderate Alzheimer disease were randomized to receive placebo (n=15) or LY450139 (100mg[n=22] or 140mg[n=14]), with 43 completing the treatment phase. Intervention: The LY450139 groups received 60 mg/d for 2 weeks, then 100 mg/d for 6 weeks, and then either 100 or 140 mg/d for 6 additional weeks. Main Outcome Measures: Primary outcome measures were adverse events, plasma and cerebrospinal fluid Aγ levels, vital signs, electrocardiographic data, and laboratory safety test results. Secondary outcome measures included the Alzheimer's Disease Assessment Scale cognitive subscale and the Alzheimer's Disease Cooperative Study Activities of Daily Living Scale. Results: Group differences were seen in skin and subcutaneous tissue concerns (P=.05), including 3 possible drug rashes and 3 reports of hair color change in the treatment groups. There were 3 adverseevent-relateddis continuations, including 1 transient bowel obstruction. The plasma Aβ40 concentration was reduced by 58.2% for the 100-mg group and 64.6% for the 140-mg group (P<.001). No significant reduction was seen in cerebro spinal fluid Aβ levels. No group differences were seen in cognitive or functional measures. Conclusions: LY450139 was generally well tolerated at doses of up to 140 mg/d for 14 weeks, with several findings indicating the need for close clinical monitoring in future studies. Decreases in plasma Aβ concentrations were consistent with inhibition of γ-secretase. [ABSTRACT FROM AUTHOR]

Context: Impairments of color discrimination (CD) and contrast sensitivity are established signs of Parkinson disease (PD), but their temporal evolution has not been studied. Objective: To determine whether there is progressive, longitudinal deterioration of color discrimination (CD) and contrast sensitivity (CS) in PD. Design: A prospective study. Setting: Tertiary care center–based sample of PD patients without dementia with normal visual acuity (Snellen fraction >0.6 in the best eye). Main Outcome Measures: With a mean ± SD interval of 19.8 ± 2.8 months, the following tests were applied twice in 28 patients: the Lanthony D15 test and the Farnsworth Munsell 100 Hue test as tests of CD and the monocular and binocular Pelli-Robson test and the binocular Vistech tables as tests of CS. Results: There was deterioration of both CD (Farnsworth Munsell 100 hue test: P = .002) and CS (binocular Vistech test at a spatial frequency of 6 cycles per degree, P<.001). Both deficits correlated with age, and the chromatic deficit additionally correlated with higher impairment of motor function (Unified Parkinson's Disease Rating Scale motor section, P = .04) and activities of daily life (Unified Parkinson's Disease Rating Scale activities of daily living section, P = .006). Patients with the highest pathologic psychiatric rating score (Brief Psychiatric Rating Scale) performed worse on both CS (P = .02) and CD (P = .01) at the second examination. Conclusions: Impairments of CD and CS in PD are progressive over time. Visual deficits may influence overall motor function and lead to enhanced motor impairment. [ABSTRACT FROM AUTHOR]

Background: Abnormal involuntary movements (dyskinesias) are common in patients with Parkinson disease (PD) as a consequence of the disease and dopaminergic replacement therapy. Early morning off-medication choreic dyskinesias have been recently reported after fetal dopaminergic cell transplantations in patients with advanced PD. Objective: To determine the frequency and severity of the early morning off-medication dyskinesias in consecutive patients with advanced PD and an insufficient response to medical management before they undergo neurosurgery. Methods: Consecutive patients with advanced idiopathic PD were examined and videotaped before undergoing neurosurgery that included pallidotomy, fetal transplantation, or deep brain stimulation. The examination took place in the morning in the practically defined off state, at least 12 hours after the last dose of dopaminergic drugs. Parkinson disease was characterized using the Unified Parkinson's Disease Rating Scale and the Hoehn and Yahr stage. Dyskinesias were rated with the Abnormal Involuntary Movements Scale and the Rush Dyskinesia Rating Scale. Patients' characteristics and medications were compared using the Wilcoxon rank sum and the Fisher exact tests. Results: Of 68 consecutive patients (44 [65%] men and 24 [35%] women), 11 (16%) had early morning off-medication dyskinesia, with a 95% upper confidence limit of 24%. Focal dystonia was the most common off-medication dyskinesia, and occurred in 10 patients (15%), with a 95% upper confidence limit of 22%; and off-choreic dyskinesia occurred in 1 patient (1.5%), with a 95% upper confidence limit of 4%. There was no difference in PD medications between the patients with and those without dyskinesias. Conclusions: The most common form of off-medication dyskinesia seen in patients with advanced PD is dystonia. Early morning off-medication choreic dyskinesias are rare but do occur in patients with advanced PD before surgical intervention. The presence and t... [ABSTRACT FROM AUTHOR]

Background: Visual hallucinations in Parkinson disease (PD) occur in approximately one third of patients treated long-term with dopaminergic medications. In Alzheimer disease, hallucinations and psychosis have been linked to increased representations of B2/B2 homozyogotes for the dopamine receptor gene DRD1 and 1/1 or 2/2 homozygotes for DRD3. In addition, a previous study of PD patients with and without hallucinations did not show differences in D2 and D3 polymorphisms, although careful case-control matching was not performed. Another study linked the apolipoprotein E4 (APOE4) allele to hallucinations in PD. Objective: To determine whether the frequency of dopamine receptor genetic variants and APOE alleles in patients with PD with and without chronic visual hallucinations resembles the pattern previously documented in patients with Alzheimer disease. Methods: We conducted a case-control study of 44 patients with PD and chronic hallucinations and 44 patients with PD who had never hallucinated. Cases and controls were matched for current age and medications. DNA was isolated from blood samples and assayed for DRD1, DRD2, DRD3, DRD4, and APOE polymorphisms. Receptor polymorphisms were genotyped by polymer-ase chain reaction. Genotypes in hallucinators and non-hallucinators were compared using Mantel-Haenszel tests... [ABSTRACT FROM AUTHOR]

Objective: To study the frequency and severity of acute orthostatic hypotension (OH) in patients with Parkinson's disease who are starting dopamine agonist therapy. Patients and Methods: In the context of an outpatient clinical practice, 29 consecutive patients with Parkinson's disease who were starting dopamine agonist therapy were brought into the clinic for their first dose of agonist. After a baseline supine and standing blood pressure assessment, patients were given a test dose of either pergolide mesylate (0.025, 0.05, 0.125, or 0.25 mg), pramipexole dihydrochloride (0.125 mg), or ropinirole hydrochloride (0.125 or 0.25 mg). At 3 selected times, blood pressure readings were repeated in the supine and standing positions. Main Outcome Measure: Orthostatic hypotension was defined as a drop in either systolic blood pressure of more than 25 mm Hg or diastolic pressure of more than 10 mm Hg. Patients with OH before the administration of the dopamine agonist were excluded. Results: Ten subjects (34%) met the criteria for acute OH. There was no evidence that OH was related to the use of a specific dopamine agonist or the concurrent use of levodopa. Of the patients who met the criteria for OH, only 3 (30%) had symptoms of OH, such as lightheadedness or general malaise. Conclusions: Acute OH occurs frequently when starting dopamine agonist therapy in Parkinson's disease, but is frequently not appreciated by patients. Knowledge of acute blood pressure responses may be useful when making decisions regarding agonist titration schedules in clinical practice. [ABSTRACT FROM AUTHOR]