Several concepts, which in the aggregate get might be used to account for "resilience" against age- and disease-related changes, have been the subject of much research. These include brain reserve, cognitive reserve, and brain maintenance. However, different investigators have use these terms in different ways, and there has never been an attempt to arrive at consensus on the definition of these concepts. Furthermore, there has been confusion regarding the measurement of these constructs and the appropriate ways to apply them to research. Therefore the reserve, resilience, and protective factors professional interest area, established under the auspices of the Alzheimer's Association, established a whitepaper workgroup to develop consensus definitions for cognitive reserve, brain reserve, and brain maintenance. The workgroup also evaluated measures that have been used to implement these concepts in research settings and developed guidelines for research that explores or utilizes these concepts. The workgroup hopes that this whitepaper will form a reference point for researchers in this area and facilitate research by supplying a common language.

We conclude that higher adherence to the MeDi is associated with a reduction in risk for AD.

Context Both higher adherence to a Mediterranean-type diet and more physical activity have been independently associated with lower Alzheimer disease (AD) risk but their combined association has not been investigated.Objective To investigate the combined association of diet and physical activity with AD risk. Design, Setting, and PatientsProspective cohort study of 2 cohorts comprising 1880 community-dwelling elders without dementia living in New York, New York, with both diet and physical activity information available. Standardized neurological and neuropsychological measures were administered approximately every 1.5 years from 1992 through 2006. Adherence to a Mediterranean-type diet (scale of 0-9; trichotomized into low, middle, or high; and dichotomized into low or high) and physical activity (sum of weekly participation in various physical activities, weighted by the type of physical activity [light, moderate, vigorous]; trichotomized into no physical activity, some, or much; and dichotomized into low or high), separately and combined, were the main predictors in Cox models. Models were adjusted for cohort, age, sex, ethnicity, education, apolipoprotein E genotype, caloric intake, body mass index, smoking status, depression, leisure activities, a comorbidity index, and baseline Clinical Dementia Rating score. Main Outcome Measure Time to incident AD.Results A total of 282 incident AD cases occurred during a mean (SD) of 5.4 (3.3) years of follow-up. When considered simultaneously, both Mediterranean-type diet adherence (compared with low diet score, hazard ratio [HR] for middle diet score was 0.98 [95% confidence interval {CI}, 0.72-1.33]; the HR for high diet score was 0.60 [95% CI, 0.42-0.87]; P=.008 for trend) and physical activity (compared with no physical activity, the HR for some physical activity was 0.75 [95% CI, 0.54-1.04]; the HR for much physical activity was 0.67 [95% CI, 0.47-0.95]; P=.03 for trend) were associated with lower AD risk. Compared with individuals neither adhering to the diet nor participating in physical activity (low diet score and no physical activity; absolute AD risk of 19%), those both adhering to the diet and participating in physical activity (high diet score and high physical activity) had a lower risk of AD (absolute risk, 12%; HR, 0.65 [95% CI, 0.44-0.96]; P=.03 for trend). ConclusionIn this study, both higher Mediterranean-type diet adherence and higher physical activity were independently associated with reduced risk for AD.

The data suggest that engagement in leisure activities may reduce the risk of incident dementia, possibly by providing a reserve that delays the onset of clinical manifestations of the disease.

Context Higher adherence to a Mediterranean-type diet is linked to lower risk for mortality and chronic diseases, but its association with cognitive decline is unclear. Objective To investigate the association of a Mediterranean diet with change in cognitive performance and risk for dementia in elderly French persons. Design, Setting, and Participants Prospective cohort study of 1410 adults (Ն65 years) from Bordeaux, France, included in the Three-City cohort in 2001-2002 and reexamined at least once over 5 years. Adherence to a Mediterranean diet (scored as 0 to 9) was computed from a food frequency questionnaire and 24-hour recall. Main Outcome Measures Cognitive performance was assessed on 4 neuropsychological tests: the Mini-Mental State Examination (MMSE), Isaacs Set Test (IST), Benton Visual Retention Test (BVRT), and Free and Cued Selective Reminding Test (FCSRT). Incident cases of dementia (n=99) were validated by an independent expert committee of neurologists. Results Adjusting for age, sex, education, marital status, energy intake, physical activity, depressive symptomatology, taking 5 medications/d or more, apolipoprotein E genotype, cardiovascular risk factors, and stroke, higher Mediterranean diet score was associated with fewer MMSE errors (␤=−0.006; 95% confidence interval [CI], −0.01 to −0.0003; P=.04 for 1 point of the Mediterranean diet score). Performance on the IST, BVRT, or FCSRT over time was not significantly associated with Mediterranean diet adherence. Greater adherence as a categorical variable (score 6-9) was not significantly associated with fewer MMSE errors and better FCSRT scores in the entire cohort, but among individuals who remained free from dementia over 5 years, the association for the highest compared with the lowest group was significant

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The concept of cognitive reserve (CR) suggests that innate intelligence or aspects of life experience like educational or occupational attainments may supply reserve, in the form of a set of skills or repertoires that allows some people to cope with progressing Alzheimer's disease (AD) pathology better than others. There is epidemiological evidence that lifestyle characterized by engagement in leisure activities of intellectual and social nature is associated with slower cognitive decline in healthy elderly and may reduce the risk of incident dementia. There is also evidence from functional imaging studies that subjects engaging in such leisure activities can clinically tolerate more AD pathology. It is possible that aspects of life experience like engagement in leisure activities may result in functionally more efficient cognitive networks and therefore provide a CR that delays the onset of clinical manifestations of dementia.The CR hypothesis suggests that there are individual differences in the ability to cope with AD pathology (Stern, 2002). For example, Katzman et al. (1989) described cases of cognitively normal, elderly women who were discovered to have advanced AD pathology in their brains at death. They speculated these women did not express the clinical features of AD because their brains were larger than average. About 25% of subjects who during autopsy fulfill pathologic criteria for AD and were assessed and followed in wellcharacterized cohorts were clinically intact during life (Ince, 2001). Similarly, most clinicians are aware of the fact that a stroke of a given magnitude can produce profound impairment in 1 patient and while having minimal effect on another. Something must account for the disjunction between the degree of brain damage and its outcome, and the concept of reserve has been proposed to serve this purpose.Innate intelligence or aspects of life experience like educational or occupational attainment may supply reserve, in the form of a set of skills or repertoires that allows some people to cope with pathology better than others.Epidemiological data supporting the CR hypothesis include observations that lower educational and occupational attainment is associated with increased risk for incident dementia (Stern et al., 1994). Similarly, lower linguistic ability (as expressed by idea density and grammatical complexity) in early life and childhood mental ability scores are strong predictors of poor cognitive function and dementia in late life (Snowdon et al., 1997;Whalley et al., 2000). This is consistent with the prediction that people with more reserve can cope with advancing AD pathology longer before it is expressed clinically. In addition it has been shown that AD patients with higher educational and occupational attainment have more rapid cognitive decline than those with lower attainment, consistent with the idea that,

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