Mild cognitive impairment (MCI) represents a transitional stage between healthy aging and dementia, and affects 10–15% of the population over the age of 65. The failure of drug trials in Alzheimer’s disease (AD) treatment has shifted researchers’ focus toward delaying progression from MCI to dementia, which would reduce the prevalence and costs of dementia profoundly. Diagnostic criteria for MCI increasingly emphasize the need for positive biomarkers to detect preclinical AD. The phenomenology of MCI comprises lower quality-of-life, greater symptoms of depression, and avoidant coping strategies including withdrawal from social engagement. Neurobiological features of MCI are hypoperfusion and hypometabolism in temporoparietal cortices, medial temporal lobe atrophy particularly in rhinal cortices, elevated tau and phosphorylated tau and decreased Aβ₄₂in cerebrospinal fluid, and brain Aβ₄₂deposition. Elevated tau can be identified in MCI, particularly in the entorhinal cortex, using positron emission tomography, and analysis of signal complexity using electroencephalography or magnetoencephalography holds promise as a biomarker. Assessment of MCI also relies on cognitive screening and neuropsychological assessment, but there is an urgent need for standardized cognitive tests to capitalize on recent discoveries in cognitive neuroscience that may lead to more sensitive measures of MCI. Cholinesterase inhibitors are frequently prescribed for MCI, despite the lack of evidence for their efficacy. Exercise and diet interventions hold promise for increasing reserve in MCI, and group psychoeducational programs teaching practical memory strategies appear effective. More work is needed to better understand the phenomenology and neurobiology of MCI, and how best to assess it and delay progression to dementia.

This article considers the scientific process whereby new and better clinical tests of executive function might be developed, and what form they might take. We argue that many of the traditional tests of executive function most commonly in use (e.g., the Wisconsin Card Sorting Test; Stroop) are adaptations of procedures that emerged almost coincidentally from conceptual and experimental frameworks far removed from those currently in favour, and that the prolongation of their use has been encouraged by a sustained period of concentration on “construct-driven” experimentation in neuropsychology. This resulted from the special theoretical demands made by the field of executive function, but was not a necessary consequence, and may not even have been a useful one. Whilst useful, these tests may not therefore be optimal for their purpose. We consider as an alternative approach a function-led development programme which in principle could yield tasks better suited to the concerns of the clinician because of the transparency afforded by increased “representativeness” and “generalisability.” We further argue that the requirement of such a programme to represent the interaction between the individual and situational context might also provide useful constraints for purely experimental investigations. We provide an example of such a programme with reference to the Multiple Errands and Six Element tests. (JINS, 2006,12, 194–209.)

There is an urgent need to identify lifestyle activities that reduce functional decline and dementia associated with population aging. The goals of this article are to review critically the evidence on the benefits associated with formal volunteering among older adults, propose a theoretical model of how volunteering may reduce functional limitations and dementia risk, and offer recommendations for future research. Database searches identified 113 papers on volunteering benefits in older adults, of which 73 were included. Data from descriptive, cross-sectional, and prospective cohort studies, along with 1 randomized controlled trial, most consistently reveal that volunteering is associated with reduced symptoms of depression, better self-reported health, fewer functional limitations, and lower mortality. The extant evidence provides the basis for a model proposing that volunteering increases social, physical, and cognitive activity (to varying degrees depending on characteristics of the volunteer placement) which, through biological and psychological mechanisms, leads to improved functioning; we further propose that these volunteering-related functional improvements should be associated with reduced dementia risk. Recommendations for future research are that studies (a) include more objective measures of psychosocial, physical, and cognitive functioning; (b) integrate qualitative and quantitative methods in prospective study designs; (c) explore further individual differences in the benefits associated with volunteering; (d) include occupational analyses of volunteers' specific jobs in order to identify their social, physical, and cognitive complexity; (e) investigate the independent versus interactive health benefits associated with volunteering relative to engagement in other forms of activity; and (f) examine the relationship between volunteering and dementia risk.

Purpose: To assess the safety and efficacy of intensive methotrexate-based chemotherapy followed by high-dose chemotherapy (HDT) with autologous stem-cell rescue in patients with newly diagnosed primary CNS lymphoma (PCNSL). Patients and Methods: Twenty-eight patients received induction chemotherapy using high-dose systemic methotrexate (3.5 g/m²) and cytarabine (3 g/m² daily for 2 days). Fourteen patients with chemosensitive disease evident on neuroimaging then received high-dose therapy using carmustine, etoposide, cytarabine, and melphalan with autologous stem-cell rescue. Results: The objective response rate to the induction-phase chemotherapy was 57%, and median overall survival is not yet assessable, with a median follow-up time of 28 months. The overall median event-free survival time is 5.6 months for all patients and 9.3 months for 14 patients who underwent transplantation. Six of these 14 patients (43%) remained disease-free at last follow-up. Treatment was well tolerated; there was one transplantation-related death. Prospective neuropsychologic evaluations have revealed no evidence of treatment-related neurotoxicity. Conclusion: This treatment approach is feasible in patients with newly diagnosed PCNSL without evidence of significant related neurotoxicity. Although the transplantation results are similar to those achieved in patients with aggressive or poor-prognosis systemic lymphoma, the low response rate to induction chemotherapy and the significant number of patients who experienced relapse soon after HDT suggest that more aggressive induction chemotherapy may be warranted.