Alzheimer Disease: McDonald S

Tariot PN, Farlow MR, Grossberg GT, Graham SM, McDonald S, Gergel I, Anonymous00181. · Department of Psychiatry, University of Rochester Medical Center, Monroe Community Hospital, Rochester, NY 14620, USA. · JAMA. · Pubmed #14734594 links to  free full text

Abstract: CONTEXT: Memantine is a low- to moderate-affinity, uncompetitive N-methyl-D-aspartate receptor antagonist. Controlled trials have demonstrated the safety and efficacy of memantine monotherapy for patients with moderate to severe Alzheimer disease (AD) but no controlled trials of memantine in patients receiving a cholinesterase inhibitor have been performed. OBJECTIVE: To compare the efficacy and safety of memantine vs placebo in patients with moderate to severe AD already receiving stable treatment with donepezil. DESIGN, SETTING, AND PARTICIPANTS: A randomized, double-blind, placebo-controlled clinical trial of 404 patients with moderate to severe AD and Mini-Mental State Examination scores of 5 to 14, who received stable doses of donepezil, conducted at 37 US sites between June 11, 2001, and June 3, 2002. A total of 322 patients (80%) completed the trial. INTERVENTIONS: Participants were randomized to receive memantine (starting dose 5 mg/d, increased to 20 mg/d, n = 203) or placebo (n = 201) for 24 weeks. MAIN OUTCOME MEASURES: Change from baseline on the Severe Impairment Battery (SIB), a measure of cognition, and on a modified 19-item AD Cooperative Study-Activities of Daily Living Inventory (ADCS-ADL19). Secondary outcomes included a Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC-Plus), the Neuropsychiatric Inventory, and the Behavioral Rating Scale for Geriatric Patients (BGP Care Dependency Subscale). RESULTS: The change in total mean (SE) scores favored memantine vs placebo treatment for SIB (possible score range, 0-100), 0.9 (0.67) vs -2.5 (0.69), respectively (P<.001); ADCS-ADL19 (possible score range, 0-54), -2.0 (0.50) vs -3.4 (0.51), respectively (P =.03); and the CIBIC-Plus (possible score range, 1-7), 4.41 (0.074) vs 4.66 (0.075), respectively (P =.03). All other secondary measures showed significant benefits of memantine treatment. Treatment discontinuations because of adverse events for memantine vs placebo were 15 (7.4%) vs 25 (12.4%), respectively. CONCLUSIONS: In patients with moderate to severe AD receiving stable doses of donepezil, memantine resulted in significantly better outcomes than placebo on measures of cognition, activities of daily living, global outcome, and behavior and was well tolerated. These results, together with previous studies, suggest that memantine represents a new approach for the treatment of patients with moderate to severe AD.

Henry JD, Ruffman T, McDonald S, O'Leary MA, Phillips LH, Brodaty H, Rendell PG. · School of Psychology, University of New South Wales, Sydney, NSW 2052, Australia. · Neuropsychologia. · Pubmed #18241898 No free full text.

Abstract: The neural substrates that subserve decoding of different emotional expressions are subject to different rates of degeneration and atrophy in Alzheimer's disease (AD), and there is therefore reason to anticipate that a differentiated profile of affect recognition impairment may emerge. However, it remains unclear whether AD differentially affects the recognition of specific emotions. Further, there is only limited research focused on whether affect recognition deficits in AD generalize to more ecologically valid stimuli. In the present study, relatively mild AD participants (n=24), older controls (n=30) and younger controls (n=30) were administered measures of affect recognition. Significant AD deficits were observed relative to both the younger and older control groups on a measure that involved labeling of static images of facial affect. AD deficits on this measure were observed in relation to all emotions assessed (anger, sadness, happiness, surprise and fear), with the exception of disgust, which was preserved even relative to the younger adult group. The relative preservation of disgust could not be attributed to biases in the choice of labels made, and it is suggested instead that this finding might reflect the relative sparing of the basal ganglia in AD. No significant AD effect was observed for the more ecologically valid measure that involved dynamic displays of facial expressions, in conjunction with paralinguistic and body movement cues, although a trend for greater AD difficulty was observed.

Nash S, Henry JD, McDonald S, Martin I, Brodaty H, Peek-O'Leary MA. · School of Psychology, University of New South Wales, Sydney 2052, Australia. · J Int Neuropsychol Soc. · Pubmed #17942023 No free full text.

Abstract: Individuals with Alzheimer's disease (AD) experience difficulties with socioemotional functioning, and it has been proposed that cognitive disinhibition may be one potential mechanism that contributes to difficulties in this area. To test this possibility, twenty individuals with AD and 20 demographically matched controls were administered self-report measures of depression, emotion regulation and empathy, in addition to a behavioral measure that has proven to be very sensitive to inhibitory failures (the Hayling Sentence Completion Test). Relative to controls AD participants exhibited increased inhibitory failures on the Hayling, and self-reported significantly reduced cognitive empathy, but did not differ with respect to affective empathy, depression or perceived capacity for emotion regulation. Controlling for general cognitive status, in the AD (but not the control) group, reduced cognitive inhibition was associated with lower levels of depression. The theoretical and practical implications of these results are discussed.

Peskind ER, Potkin SG, Pomara N, Ott BR, Graham SM, Olin JT, McDonald S. · Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine and Veterans Affairs Northwest Network Mental Illness Research, Education, and Clinical Center, Seattle, WA 98108, USA. · Am J Geriatr Psychiatry. · Pubmed #16861375 No free full text.

Abstract: OBJECTIVE: The objective of this study was to compare the efficacy and safety of the moderate-affinity, uncompetitive N-methyl-d-aspartate receptor antagonist, memantine, versus placebo in patients with mild to moderate Alzheimer disease (AD). METHOD: This was a randomized, double-blind, placebo-controlled clinical trial conducted at 42 U.S. sites. Participants were 403 outpatients with mild to moderate AD and Mini-Mental State Examination scores of 10-22 randomized to memantine (20 mg/day; N=201) or placebo (N=202) for 24 weeks. Primary outcomes were change from baseline at 24 weeks on the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog), a measure of cognition, and on the Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC-Plus), a global measure. Secondary outcomes included change on the Neuropsychiatric Inventory (NPI) and the Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL(23)), measures of behavior and function, respectively. RESULTS: Most (82.4%) participants completed the trial. Memantine resulted in significantly better outcomes than placebo on measures of cognition, global status, and behavior when based on the protocol-specified primary last observation carried forward imputation as well as a mixed-models repeated-measures approach applied to the continuous outcomes. Treatment discontinuations because of adverse events for memantine versus placebo were 19 (9.5%) and 10 (5.0%), respectively. CONCLUSIONS: These results support the safety and efficacy of memantine for the treatment of mild to moderate AD.