The authors trained 4 older adults with probable Alzheimer’s disease to recall a name-face-occupation association using the spaced retrieval technique. Six training sessions were administered over a 2-week period. On each trial, participants selected a target photograph and stated the target name and occupation at increasingly longer retention intervals, contingent upon successful recall. Two transfer tasks were included to determine whether the trained association transferred to the person whose picture served as the training stimulus. Results yielded a positive effect of spaced retrieval on memory for the trained association. Analyses of errors revealed that participants remembered the target person’s occupation more often than his or her name. There was modest evidence of transfer of the name-face-occupation association to the actual person. Implications of these data for memory remediation and quality of life in cognitively impaired older adults are considered.

J Genet Psychol. 2010 Apr-Jun;171(2):168-81.

Cherry KE, Walvoord AA, Hawley KS.

Louisiana State University, Department of Psychology, 236 Audubon Hall, Baton Rouge, LA 70803, USA. pskatie@lsu.edu

The brain is a highly compartmentalized organ exceptionally susceptible to accumulation of metabolic errors. Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease of the elderly and is characterized by regional specificity of neural aberrations associated with higher cognitive functions. Aluminum (Al) is the most abundant neurotoxic metal on earth, widely bioavailable to humans and repeatedly shown to accumulate in AD-susceptible neuronal foci. In spite of this, the role of Al in AD has been heavily disputed based on the following claims: 1) bioavailable Al cannot enter the brain in sufficient amounts to cause damage, 2) excess Al is efficiently excreted from the body, and 3) Al accumulation in neurons is a consequence rather than a cause of neuronal loss. Research, however, reveals that: 1) very small amounts of Al are needed to produce neurotoxicity and this criterion is satisfied through dietary Al intake, 2) Al sequesters different transport mechanisms to actively traverse brain barriers, 3) incremental acquisition of small amounts of Al over a lifetime favors its selective accumulation in brain tissues, and 4) since 1911, experimental evidence has repeatedly demonstrated that chronic Al intoxication reproduces neuropathological hallmarks of AD. Misconceptions about Al bioavailability may have mislead scientists regarding the significance of Al in the pathogenesis of AD. The hypothesis that Al significantly contributes to AD is built upon very solid experimental evidence and should not be dismissed. Immediate steps should be taken to lessen human exposure to Al, which may be the single most aggravating and avoidable factor related to AD.

Tomljenovic L .

Neural Dynamics Research Group, Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, BC, Canada.

BACKGROUND: Agitation is a common and distressing symptom in patients with Alzheimer’s disease. Cholinesterase inhibitors improve cognitive outcomes in such patients, but the benefits of these drugs for behavioral disturbances are unclear.

METHODS: We randomly assigned 272 patients with Alzheimer’s disease who had clinically significant agitation and no response to a brief psychosocial treatment program to receive 10 mg of donepezil per day (128 patients) or placebo (131 patients) for 12 weeks. The primary outcome was a change in the score on the Cohen-Mansfield Agitation Inventory (CMAI) (on a scale of 29 to 203, with higher scores indicating more agitation) at 12 weeks.

RESULTS: There was no significant difference between the effects of donepezil and those of placebo on the basis of the change in CMAI scores from baseline to 12 weeks (estimated mean difference in change [the value for donepezil minus that for placebo], -0.06; 95% confidence interval [CI], -4.35 to 4.22). Twenty-two of 108 patients (20.4%) in the placebo group and 22 of 113 (19.5%) in the donepezil group had a reduction of 30% or greater in the CMAI score (the value for donepezil minus that for placebo, -0.9 percentage point; 95% CI, -11.4 to 9.6). There were also no significant differences between the placebo and donepezil groups in scores for the Neuropsychiatric Inventory, the Neuropsychiatric Inventory Caregiver Distress Scale, or the Clinician’s Global Impression of Change.

CONCLUSIONS: In this 12-week trial, donepezil was not more effective than placebo in treating agitation in patients with Alzheimer’s disease. (ClinicalTrials.gov number, NCT00142324 [ClinicalTrials.gov].).

N Engl J Med. 2007 Oct 4;357(14):1382-92.

Howard RJ, Juszczak E, Ballard CG, Bentham P, Brown RG, Bullock R, Burns AS, Holmes C, Jacoby R, Johnson T, Knapp M, Lindesay J, O’Brien JT, Wilcock G, Katona C, Jones RW, DeCesare J, Rodger M; CALM-AD Trial Group.

Medical Research Council Neurogeneration Research Centre, Institute of Psychiatry, King’s College London, London, United Kingdom. robert.howard@iop.kcl.ac.uk

Comment in:

• ACP J Club. 2008 Mar-Apr;148(2):33.
• Evid Based Ment Health. 2008 Aug;11(3):84.
• N Engl J Med. 2007 Oct 4;357(14):1441-3.