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ABSTRACT: Agitation in Alzheimer's disease (AD) is common and associated with poor patient life-quality and carer distress. The best evidence-based pharmacological treatments are antipsychotics which have limited benefits with increased morbidity and mortality. There are no memantine trials in clinically significant agitation but post-hoc analyses in other populations found reduced agitation. We tested the primary hypothesis, memantine is superior to placebo for clinically significant agitation, in patients with moderate-to-severe AD.
We recruited 153 participants with AD and clinically significant agitation from care-homes or hospitals for a double-blind randomised-controlled trial and 149 people started the trial of memantine versus placebo. The primary outcome was 6 weeks mixed model autoregressive analysis of Cohen-Mansfield Agitation Inventory (CMAI). Secondary outcomes were: 12 weeks CMAI; 6 and 12 weeks Neuropsychiatric symptoms (NPI), Clinical Global Impression Change (CGI-C), Standardised Mini Mental State Examination, Severe Impairment Battery. Using a mixed effects model we found no significant differences in the primary outcome, 6 weeks CMAI, between memantine and placebo (memantine lower -3.0; -8.3 to 2.2, p = 0.26); or 12 weeks CMAI; or CGI-C or adverse events at 6 or 12 weeks. NPI mean difference favoured memantine at weeks 6 (-6.9; -12.2 to -1.6; p = 0.012) and 12 (-9.6; -15.0 to -4.3 p = 0.0005). Memantine was significantly better than placebo for cognition. The main study limitation is that it still remains to be determined whether memantine has a role in milder agitation in AD.
Memantine did not improve significant agitation in people with in moderate-to-severe AD. Future studies are urgently needed to test other pharmacological candidates in this group and memantine for neuropsychiatric symptoms.
ClinicalTrials.gov NCT00371059.
International Standard Randomised Controlled Trial 24953404.
PLoS ONE 01/2012; 7(5):e35185. · 4.09 Impact Factor
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ABSTRACT: to examine the effect of medications with anticholinergic effects on cognitive impairment and deterioration in Alzheimer's dementia (AD).
cognitive function was measured at baseline and at 6- and 18-month follow-up using the Mini-Mental State Exam (MMSE), the Severe Impairment Battery (SIB) and the Alzheimer's Disease Assessment Battery, Cognitive subsection (ADAS-COG) in a cohort study of 224 participants with AD. Baseline anticholinergic Burden score (ABS) was measured using the Anticholinergic Burden scale and included all prescribed and over the counter medication.
the sample was 224 patients with Alzheimer's dementia and 71.4% were women. Their mean age was 81.0 years [SD 7.4 (range 55-98)]. The mean number of medications taken was 3.6 (SD 2.4) and the mean anticholinergic load was 1.1 (SD 1.4, range 0-7). The total number of drugs taken and anticholinergic load correlated (rho = 0.44; P < 0.01). There were no differences in MMSE and other cognitive functioning at either 6 or 18 months after adjusting for baseline cognitive function, age, gender and use of cholinesterase inhibitors between those with, and those without high anticholinergenic load.
medications with anticholinergic effect in patients with AD were not found to effect deterioration in cognition over the subsequent 18 months. Our study did not support a continuing effect of these medications on people with AD who are established on them.
Age and Ageing 09/2011; 40(6):730-5. · 3.09 Impact Factor
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ABSTRACT: To determine whether the use of medications with possible and definite anticholinergic activity increases the risk of cognitive impairment and mortality in older people and whether risk is cumulative.
A 2-year longitudinal study of participants enrolled in the Medical Research Council Cognitive Function and Ageing Study between 1991 and 1993.
Community-dwelling and institutionalized participants.
Thirteen thousand four participants aged 65 and older.
Baseline use of possible or definite anticholinergics determined according to the Anticholinergic Cognitive Burden Scale and cognition determined using the Mini-Mental State Examination (MMSE). The main outcome measure was decline in the MMSE score at 2 years.
At baseline, 47% of the population used a medication with possible anticholinergic properties, and 4% used a drug with definite anticholinergic properties. After adjusting for age, sex, educational level, social class, number of nonanticholinergic medications, number of comorbid health conditions, and cognitive performance at baseline, use of medication with definite anticholinergic effects was associated with a 0.33-point greater decline in MMSE score (95% confidence interval (CI)=0.03-0.64, P=.03) than not taking anticholinergics, whereas the use of possible anticholinergics at baseline was not associated with further decline (0.02, 95% CI=-0.14-0.11, P=.79). Two-year mortality was greater for those taking definite (OR=1.68; 95% CI=1.30-2.16; P<.001) and possible (OR=1.56; 95% CI=1.36-1.79; P<.001) anticholinergics.
The use of medications with anticholinergic activity increases the cumulative risk of cognitive impairment and mortality.
Journal of the American Geriatrics Society 06/2011; 59(8):1477-83. · 3.74 Impact Factor
