Efficacy of cognitive rehabilitation in patients with mild cognitive impairment treated with cholinesterase inhibitors. Reality orientation therapy combined with cholinesterase inhibitors in Alzheimer's disease: randomised controlled trial. Cognitive rehabilitation of mildly impaired Alzheimer disease patients on cholinesterase inhibitors. Long-term citicoline (cytidine diphosphate choline) use in patients with vascular dementia: neuroimaging and neuropsychological outcomes. Donepezil for cognitive impairment in Parkinson's disease: a randomised controlled study. CDP-choline in the treatment of chronic cerebrovasculopathies. Effects of galantamine on working memory and global functioning in patients with mild cognitive impairment: a double-blind placebo-controlled study. Rivastigmine and donepezil treatment in moderate to moderately-severe Alzheimer's disease over a 2-year period. Lack of efficacy of citalopram in children with autism spectrum disorders and high levels of repetitive behavior: citalopram ineffective in children with autism.
Individuals who have Mild Cognitive Impairment (MCI) may be in a transitional stage between aging and Alzheimer's disease (AD). The high rate of conversion from MCI to AD makes early treatment an important clinical issue. Recent evidence suggests that cognitive training intervention may reduce the rate of progression to AD.
                To evaluate the efficacy of a NeuroPsychological Training (TNP) in patients with MCI who are treated with cholinesterase inhibitors (ChEIs), compared with patients MCI treated only with ChEIs and patients not treated, in a longitudinal, one year follow-up study.
                One year longitudinal and retrospective comparison study of neuropsychological performances in 59 subjects affected by Mild Cognitive Impairment (MCI) according to Petersen's criteria. Fifteen subjects were randomised to receive TNP plus cholinesterase inhibitors; 22 subjects cholinesterase inhibitors alone and 22 subjects no treatment. All the subjects referring memory complaints, corroborated by an informant, underwent a multidimensional assessment concerning neuropsychological, behavioural and functional characteristics, at baseline and after one year follow-up.
                Subjects without treatment maintained their cognitive, functional and behavioural status after one year; patients treated only with ChEIs improved in depressive symptoms whereas subjects treated with TNP and ChEIs showed significant improvements in different cognitive areas, such as memory, abstract reasoning and in behavioural disturbances, particularly depressive symptoms.
                A long-term TNP in ChEIs-treated MCI subjects induces additional cognitive and mood benefits. Reality orientation therapy combined with cholinesterase inhibitors has not been evaluated in patients with Alzheimer's disease.
                To perform such an evaluation.
                We randomly assigned 79 of 156 patients treated with donepezil to receive a reality orientation programme. Caregivers of the treatment group were trained to offer the programme at home 3 days a week, 30 min/day, for 25 consecutive weeks, and were invited to stimulate and involve patients in reality-based communication.
                The treatment group showed a slight improvement in Mini-Mental State Examination (MMSE) scores (mean change +0.2, s.e.=0.4) compared with a decline in the control group (mean change -1.1, s.e.=0.4; P=0.02). Similarly for the Alzheimer's Disease Assessment Scale--Cognition (treatment group mean change +0.4, s.e.=0.8; control group -2.5, s.e.=0.8; P=0.01). The intervention had an equal effect on cognition in those with mild (MMSE score > or = 20) and moderate (score <20) dementia. No significant effect was observed for behavioural and functional outcomes.
                Reality orientation enhances the effects of donepezil on cognition in Alzheimer's disease. The authors evaluated the efficacy of a new cognitive rehabilitation program on memory and functional performance of mildly impaired Alzheimer disease (AD) patients receiving a cholinesterase inhibitor.
                Twenty-five participants in the Cognitive Rehabilitation (CR) condition participated in two 45-minute sessions twice per week for 24 total sessions. CR training included face-name association tasks, object recall training, functional tasks (e.g., making change, paying bills), orientation to time and place, visuo-motor speed of processing, and the use of a memory notebook. Nineteen participants in the Mental Stimulation (MS) condition had equivalent therapist contact and number of sessions, which consisted of interactive computer games involving memory, concentration, and problem-solving skills.
                Compared with the MS condition, participants in CR demonstrated improved performance on tasks that were similar to those used in training. Gains in recall of face-name associations, orientation, cognitive processing speed, and specific functional tasks were present post-intervention and at a 3-month follow-up.
                A systematic program of cognitive rehabilitation can result in maintained improvement in performance on specific cognitive and functional tasks in mildly impaired AD patients. Cytidine diphosphate choline (citicoline) has been previously shown to have efficacy in reducing the functional impairments associated with acute stroke. Citicoline is thought to have neuroprotective benefits and has been used for the treatment of chronic cerebrovascular disorders, though its effectiveness has not been fully tested. This randomized, double-blind clinical trial was conducted to determine whether daily citicoline treatment improves neurocognitive and neuroimaging outcome over 12 months among patients diagnosed with vascular dementia (VaD).
                30 patients diagnosed with VaD, based upon NINDS-AIREN and DSM-IV criteria, were randomized and treated with either 500 mg of citicoline or placebo twice per day. Patients were assessed at baseline, and at 6, and 12 months on a battery of neurocognitive tests. Neuroimaging measures of total brain volume and subcortical/periventricular hyperintensity (SH) volume on magnetic resonance imaging (MRI) were collected at baseline and the 12-month follow-up.
                The citicoline and placebo treatment groups did not differ in their neuropsychological performance at baseline and the 12-month follow-up. Significant declines in neuropsychological performance were noted, as well as significantly increased SH and reduced total brain volumes on MRI for both groups at the 12-month follow-up.
                The efficacy of long-term citicoline treatment for cognitive impairment and neuropathological decline in those patients already meeting criteria for VaD does not appear to be substantiated by the current study.
                Copyright 2003 S. Karger AG, Basel To study the safety and efficacy of the cholinesterase inhibitor donepezil in patients with Parkinson's disease (PD) and cognitive impairment.
                This was a double blind, randomised and placebo controlled, crossover study in which 14 patients with PD and cognitive impairment received donepezil (5 or 10 mg per day) or matching placebo during two sequential periods lasting 10 weeks each. The primary outcome measures were the mini mental state examination (MMSE) score, the clinician's interview based impression of change plus caregiver input (CIBIC+) score, and the motor subscale of the unified Parkinson's disease rating scale (UPDRS).
                Two patients on donepezil (14%) dropped out after one and four weeks of the first treatment period because of peripheral cholinergic side effects, otherwise the adverse effects were few and not severe. Carryover or residual effects were not observed. Parkinsonism did not increase during donepezil treatment. After 10 weeks of treatment, the mean MMSE score was increased by 2.1(SD 2.7) points on donepezil and 0.3 (SD 3.2) points on placebo, and the CIBIC+ score was 3.3 (SD 0.9) on donepezil and 4.1 (SD 0.8) on placebo. Statistical analysis of the repeated measurements and crossover study design showed significant effects of donepezil compared with placebo for MMSE (p=0.013) and CIBIC+ (p=0.034). Five (42%) patients on donepezil and two (17%) on placebo were rated as improved on the basis of the CIBIC+ score.
                Donepezil improves cognition, and seems to be well tolerated and not to worsen parkinsonism in patients with cognitive impairment. Ninety-two patients affected by chronic cerebrovasculopathy were treated with cytidine diphosphate choline (CDP-choline) 1000 mg/day i.m. or with placebo, in a double-blind study. Two cycles of therapy of 4 weeks each were performed, with an interval of 1 week. There were 46 patients in each group with chronic cerebrovascular diseases, and the two groups were comparable as far as mental deterioration was concerned. The following psychometric tests were administered: Toulouse-Piéron (attention to non-verbal stimuli), Randt Memory test (memory), Sandoz Clinical Assessment of Geriatrics (SCAG, measurement of the behavioral and emotional control). The comparison between the two groups revealed significant improvements in the CDP-choline group compared with the placebo group in some of the attention capabilities (decrease in the number of wrong answers at the Toulouse-Piéron test), of the mnemonic capabilities ('General Information' subtest of Randt Memory test) and behavioral capabilities (SCAG 'affective disturbances' score). No side-effects were detected in the CDP-choline group. Mild cognitive impairment (MCI) causes memory impairment and executive function deficits in those with the condition. There is also some evidence that MCI patients are impaired in their daily functioning. Cholinesterase inhibitors have been widely used for patients with Alzheimer's disease (AD), with evidence of improving cognitive function. There is currently no established treatment for MCI, and cholinesterase inhibitors are beginning to be studied in these patients. Galantamine is a cholinesterase inhibitor that also has nicotinic receptor-modulating properties that has been successful in improving AD patients. This study examined the effects of galantamine in patients with MCI in areas of memory, executive functioning, and global functioning. There was a significant improvement in scores on the Functional Activities Questionnaire, which is a measure of global functioning. There were also improvements in the galantamine group on two of six measures in the Cambridge Automated Neuropsychiatric Test Assessment Battery and in immediate free recall on the California Verbal Learning Test. Randomised controlled trials that directly compare cholinesterase inhibitors for the treatment of Alzheimer's disease have been characterised by significant methodological limitations. As a consequence, they have failed to establish whether there are differences between agents in this class. To help address this question, a double-blind, randomised, controlled, multicentre trial was designed to evaluate the efficacy and tolerability of cholinesterase inhibitor treatment in patients with moderate to moderately-severe Alzheimer's disease over a 2-year period.
                Patients were randomly assigned to rivastigmine 3-12 mg/day or donepezil 5-10 mg/day. Efficacy measures comprised assessments of cognition, activities of daily living, global functioning and behavioural symptoms. Safety and tolerability assessments included adverse events and measurement of vital signs.
                In total, 994 patients received cholinesterase inhibitor treatment (rivastigmine, n = 495; donepezil, n = 499), and 57.9% of patients completed the study. The most frequent reason for premature discontinuation in both treatment groups was adverse events, primarily gastrointestinal. Adverse events were more frequent in the rivastigmine group during the titration phase, but similar in the maintenance phase. Serious adverse events were reported by 31.7% of rivastigmine- and 32.5% of donepezil-treated patients, respectively. Rivastigmine and donepezil had similar effects on measures of cognition and behaviour, but rivastigmine showed a statistically significant advantage on measures of activities of daily living and global functioning in the ITT-LOCF population. However, this was not maintained in the non-ITT-LOCF populations. In secondary subgroup analyses, AD patients who had genotypes that encoded for full expression of the butyrylcholinesterase enzyme (BuChE wt/wt; n = 226/340), who were < 75 years of age (n = 362/994) or who had symptoms suggestive of concomitant Lewy body disease (n = 49/994) showed significantly greater benefits from rivastigmine treatment.
                Cholinesterase inhibitor treatment may offer continued therapeutic benefit for up to 2 years in patients with moderate AD. Although both drugs performed similarly on cognition and behaviour, rivastigmine may provide greater benefit in activities of daily living and global functioning. Selective serotonin reuptake inhibitors are widely prescribed for children with autism spectrum disorders.
                To determine the efficacy and safety of citalopram hydrobromide therapy for repetitive behavior in children with autism spectrum disorders.
                National Institutes of Health-sponsored randomized controlled trial.
                Six academic centers, including Mount Sinai School of Medicine, North Shore-Long Island Jewish Health System, University of North Carolina at Chapel Hill, University of California at Los Angeles, Yale University, and Dartmouth Medical School.
                One hundred forty-nine volunteers 5 to 17 years old (mean [SD] age, 9.4 [3.1] years) were randomized to receive citalopram (n = 73) or placebo (n = 76). Participants had autistic spectrum disorders, Asperger disorder, or pervasive developmental disorder, not otherwise specified; had illness severity ratings of at least moderate on the Clinical Global Impressions, Severity of Illness Scale; and scored at least moderate on compulsive behaviors measured with the Children's Yale-Brown Obsessive Compulsive Scales modified for pervasive developmental disorders.
                Twelve weeks of citalopram hydrobromide (10 mg/5 mL) or placebo. The mean (SD) maximum dosage of citalopram hydrobromide was 16.5 (6.5) mg/d by mouth (maximum, 20 mg/d).
                Positive response was defined by a score of much improved or very much improved on the Clinical Global Impressions, Improvement subscale. An important secondary outcome was the score on the Children's Yale-Brown Obsessive Compulsive Scales modified for pervasive developmental disorders. Adverse events were systematically elicited using the Safety Monitoring Uniform Report Form.
                There was no significant difference in the rate of positive response on the Clinical Global Impressions, Improvement subscale between the citalopram-treated group (32.9%) and the placebo group (34.2%) (relative risk, 0.96; 95% confidence interval, 0.61-1.51; P > .99). There was no difference in score reduction on the Children's Yale-Brown Obsessive Compulsive Scales modified for pervasive developmental disorders from baseline (mean [SD], -2.0 [3.4] points for the citalopram-treated group and -1.9 [2.5] points for the placebo group; P = .81). Citalopram use was significantly more likely to be associated with adverse events, particularly increased energy level, impulsiveness, decreased concentration, hyperactivity, stereotypy, diarrhea, insomnia, and dry skin or pruritus.
                Results of this trial do not support the use of citalopram for the treatment of repetitive behavior in children and adolescents with autism spectrum disorders. Trial Registration clinicaltrials.gov Identifier: NCT00086645.
The currently available evidence supports the use of cholinesterase inhibitors in patients with PDD, with a positive impact on global assessment, cognitive function, behavioural disturbance and activities of daily living rating scales. The effect in DLB remains unclear. There is no current disaggregated evidence to support their use in CIND-PD.