We used to think that that the brain had a fixed number of cells and only lost them as time went on.  Over the past twenty years, new research has shown that the brain actually can regenerate new brain cells throughout life when given the right stimulation.  Below are select articles that provide more detail on the evidence behind brain fitness programs. 

JAMA. 2002 Feb 13;287(6):742-8.
Participation in cognitively stimulating activities and risk of incident Alzheimer disease.
Wilson RS, Mendes De Leon CF, Barnes LL, Schneider JA, Bienias JL, Evans DA, Bennett DA.
Rush Alzheimer's Disease Center, 1645 W Jackson Blvd, Suite 675, Chicago, IL 60612, USA. rwilson@rush.edu

CONTEXT: Frequent participation in cognitively stimulating activities has been hypothesized to reduce risk of Alzheimer disease (AD), but prospective data regarding an association are lacking.

OBJECTIVE: To test the hypothesis that frequent participation in cognitive activities is associated with a reduced risk of AD. DESIGN: Longitudinal cohort study with baseline evaluations performed between January 1994 and July 2001 and mean follow-up of 4.5 years.

SETTING: A total of 801 older Catholic nuns, priests, and brothers without dementia at enrollment, recruited from 40 groups across the United States. At baseline, they rated frequency of participation in common cognitive activities (eg, reading a newspaper), from which a previously validated composite measure of cognitive activity frequency was derived.

MEASURES: Clinical diagnosis of AD by a board-certified neurologist using National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association criteria and change in global and specific measures of cognitive function, compared by cognitive activity score at baseline.

RESULTS: Baseline scores on the composite measure of cognitive activity ranged from 1.57 to 4.71 (mean, 3.57; SD, 0.55), with higher scores indicating more frequent activity. During an average of 4.5 years of follow-up, 111 persons developed AD. In a proportional hazards model that controlled for age, sex, and education, a 1-point increase in cognitive activity score was associated with a 33% reduction in risk of AD (hazard ratio, 0.67; 95% confidence interval, 0.49-0.92). Results were comparable when persons with memory impairment at baseline were excluded and when terms for the apolipoprotein E epsilon4 allele and other medical conditions were added. In random-effects models that controlled for age, sex, education, and baseline level of cognitive function, a 1-point increase in cognitive activity was associated with reduced decline in global cognition (by 47%), working memory (by 60%), and perceptual speed (by 30%).

CONCLUSION: These results suggest that frequent participation in cognitively stimulating activities is associated with reduced risk of AD.

Excerpt from study: Assessment of Cognitive Activity
We used a previously established, composite measure of cognitive activity frequency in analyses. At baseline, persons were asked about time typically spent in 7 common activities that involve information processing as a central component: viewing television; listening to radio; reading newspapers; reading magazines; reading books; playing games such as cards, checkers, crosswords, or other puzzles; and going to museums. Frequency of participation in each activity was rated on a 5-point scale, as follows: 5 points, every day or about every day; 4 points, several times a week; 3 points, several times a month; 2 points, several times a year; and 1 point, once a year or less. Responses to each item were averaged to yield the composite measure.

J Epidemiol Community Health. 2003 Nov;57(11):907-13.
Leisure activities and cognitive function in middle age: evidence from the Whitehall II study.
Singh-Manoux A, Richards M, Marmot M.

International Centre for Health and Society, Department of Epidemiology and Public Health, University College London, London, UK. A.Singh-Manoux@public-health.ucl.ac.uk

OBJECTIVES: To test the hypothesis of a positive association, independent of social position, between participation in leisure activities and cognitive function in middle age. The nature of this relation is explored by first classifying leisure activities as entailing high or low cognitive effort, and then classifying them as entailing individual or social activities.

SETTING: London based office staff (Whitehall II study) in 20 civil service departments at baseline.

METHODS: Data are from the fifth wave of data collection (phase 5) of a prospective cohort study, collected through clinical examination and a self administered questionnaire. Firstly, hierarchical multiple regression was used to examine age and socioeconomic status (SES) adjusted effect of each leisure activity on cognition. Then structural equation models were used to examine the effects of two categories of leisure activities-activities entailing high or low cognitive effort and social or individual activities. All analyses are cross sectional.

RESULTS: There was an age and SES adjusted association between participation in leisure activities and cognitive function. More specifically, leisure activity entailing high cognitive effort or social interaction was associated with better cognitive ability.

CONCLUSIONS: Participation in cognitively complex or social leisure activities has an independent association with adult cognition, suggesting that seeking mental stimulation may have a beneficial effect on cognition in middle age.

Am J Geriatr Psychiatry. 2006 Jun;14(6):538-45.
Effects of a 14-day healthy longevity lifestyle program on cognition and brain function.
Small GW, Silverman DH, Siddarth P, Ercoli LM, Miller KJ, Lavretsky H, Wright BC, Bookheimer SY, Barrio JR, Phelps ME.

Department of Psychiatry and Biobehavioral Sciences and Semel Institute for Neuroscience and Human Behavior, Los Angeles, CA 90024, USA. gsmall@mednet.ucla.edu

OBJECTIVE: The objective of this study was to determine the effects of a 14-day healthy longevity lifestyle program on cognition and cerebral metabolism in people with mild age-related memory complaints.

METHODS: Seventeen nondemented subjects, aged 35-69 years (mean: 53 years, standard deviation: 10) with mild self-reported memory complaints but normal baseline memory performance scores were randomly assigned to 1) the intervention group (N = 8): a program combining a brain healthy diet plan, relaxation exercises, cardiovascular conditioning, and mental exercise (brain teasers and verbal memory training techniques); or 2) the control group (N = 9): usual lifestyle routine. Pre- and postintervention measures included self-assessments of memory ability, objective tests of cognitive performance, and determinations of regional cerebral metabolism during mental rest with [fluorine-18]fluorodeoxyglucose (FDG) positron emission tomography (PET). RESULTS: Subjects in the intervention group objectively demonstrated greater word fluency. Concomitantly, their FDG-PET scans identified a 5% decrease in activity in the left dorsolateral prefrontal cortex. The control group showed no significant change in any of the measures.

CONCLUSIONS: A short-term healthy lifestyle program combining mental and physical exercise, stress reduction, and healthy diet was associated with significant effects on cognitive function and brain metabolism. Reduced resting activity in left dorsolateral prefrontal cortex may reflect greater cognitive efficiency of a brain region involved in working memory.

JAMA. 2002 Nov 13;288(18):2271-81.
Effects of cognitive training interventions with older adults: a randomized controlled trial.
Ball K, Berch DB, Helmers KF, Jobe JB, Leveck MD, Marsiske M, Morris JN, Rebok GW, Smith DM, Tennstedt SL, Unverzagt FW, Willis SL; Advanced Cognitive Training for Independent and Vital Elderly Study Group.

Department of Psychology, University of Alabama at Birmingham, 35294-2100, USA. kball@uab.edu

CONTEXT: Cognitive function in older adults is related to independent living and need for care. However, few studies have addressed whether improving cognitive functions might have short- or long-term effects on activities related to living independently.

OBJECTIVE: To evaluate whether 3 cognitive training interventions improve mental abilities and daily functioning in older, independent-living adults. DESIGN: Randomized, controlled, single-blind trial with recruitment conducted from March 1998 to October 1999 and 2-year follow-up through December 2001. SETTING AND PARTICIPANTS: Volunteer sample of 2832 persons aged 65 to 94 years recruited from senior housing, community centers, and hospital/clinics in 6 metropolitan areas in the United States.

INTERVENTIONS: Participants were randomly assigned to 1 of 4 groups: 10-session group training for memory (verbal episodic memory; n = 711), or reasoning (ability to solve problems that follow a serial pattern; n = 705), or speed of processing (visual search and identification; n = 712); or a no-contact control group (n = 704). For the 3 treatment groups, 4-session booster training was offered to a 60% random sample 11 months later.

MAIN OUTCOME MEASURES: Cognitive function and cognitively demanding everyday functioning.

RESULTS: Thirty participants were incorrectly randomized and were excluded from the analysis. Each intervention improved the targeted cognitive ability compared with baseline, durable to 2 years (P<.001 for all). Eighty-seven percent of speed-, 74% of reasoning-, and 26% of memory-trained participants demonstrated reliable cognitive improvement immediately after the intervention period. Booster training enhanced training gains in speed (P<.001) and reasoning (P<.001) interventions (speed booster, 92%; no booster, 68%; reasoning booster, 72%; no booster, 49%), which were maintained at 2-year follow-up (P<.001 for both). No training effects on everyday functioning were detected at 2 years.

CONCLUSIONS: Results support the effectiveness and durability of the cognitive training interventions in improving targeted cognitive abilities. Training effects were of a magnitude equivalent to the amount of decline expected in elderly persons without dementia over 7- to 14-year intervals. Because of minimal functional decline across all groups, longer follow-up is likely required to observe training effects on everyday function.

JAMA. 2006 Dec 20;296(23):2805-14.
Long-term effects of cognitive training on everyday functional outcomes in older adults.
Willis SL, Tennstedt SL, Marsiske M, Ball K, Elias J, Koepke KM, Morris JN, Rebok GW, Unverzagt FW, Stoddard AM, Wright E; ACTIVE Study Group.

Department of Human Development and Family Studies, Pennsylvania State University, State College, PA 16801. slw@psu.edu

CONTEXT: Cognitive training has been shown to improve cognitive abilities in older adults but the effects of cognitive training on everyday function have not been demonstrated.

OBJECTIVE: To determine the effects of cognitive training on daily function and durability of training on cognitive abilities.

DESIGN, SETTING, AND PARTICIPANTS: Five-year follow-up of a randomized controlled single-blind trial with 4 treatment groups. A volunteer sample of 2832 persons (mean age, 73.6 years; 26% black), living independently in 6 US cities, was recruited from senior housing, community centers, and hospitals and clinics. The study was conducted between April 1998 and December 2004. Five-year follow-up was completed in 67% of the sample.

INTERVENTIONS: Ten-session training for memory (verbal episodic memory), reasoning (inductive reasoning), or speed of processing (visual search and identification); 4-session booster training at 11 and 35 months after training in a random sample of those who completed training.

MAIN OUTCOME MEASURES: Self-reported and performance-based measures of daily function and cognitive abilities.

RESULTS: The reasoning group reported significantly less difficulty in the instrumental activities of daily living (IADL) than the control group (effect size, 0.29; 99% confidence interval [CI], 0.03-0.55). Neither speed of processing training (effect size, 0.26; 99% CI, -0.002 to 0.51) nor memory training (effect size, 0.20; 99% CI, -0.06 to 0.46) had a significant effect on IADL. The booster training for the speed of processing group, but not for the other 2 groups, showed a significant effect on the performance-based functional measure of everyday speed of processing (effect size, 0.30; 99% CI, 0.08-0.52). No booster effects were seen for any of the groups for everyday problem-solving or self-reported difficulty in IADL. Each intervention maintained effects on its specific targeted cognitive ability through 5 years (memory: effect size, 0.23 [99% CI, 0.11-0.35]; reasoning: effect size, 0.26 [99% CI, 0.17-0.35]; speed of processing: effect size, 0.76 [99% CI, 0.62-0.90]). Booster training produced additional improvement with the reasoning intervention for reasoning performance (effect size, 0.28; 99% CI, 0.12-0.43) and the speed of processing intervention for speed of processing performance (effect size, 0.85; 99% CI, 0.61-1.09).

CONCLUSIONS: Reasoning training resulted in less functional decline in self-reported IADL. Compared with the control group, cognitive training resulted in improved cognitive abilities specific to the abilities trained that continued 5 years after the initiation of the intervention. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00298558.

Nature Neuroscience 7, 75-79(2003)
Increased prefrontal and parietal activity after training of working memory

Karolinska Institute, Department of Neuropediatrics, Astrid Lindgren's Children's Hospital Q2:07, 171 76 Stockholm, Sweden.

Working memory capacity has traditionally been thought to be constant. Recent studies, however, suggest that working memory can be improved by training. In this study, we have investigated the changes in brain activity that are induced by working memory training. Two experiments were carried out in which healthy, adult human subjects practiced working memory tasks for 5 weeks. Brain activity was measured with functional magnetic resonance imaging (fMRI) before, during and after training. After training, brain activity that was related to working memory increased in the middle frontal gyrus and superior and inferior parietal cortices. The changes in cortical activity could be evidence of training-induced plasticity in the neural systems that underlie working memory.

The New England Journal of Medicine, 348: 2508-2516(2003)
Leisure activities and the risk of dementia in the elderly

Verghese J, Lipton RB, Katz MJ, Hall CB, Derby CA, Kuslansky G, Ambrose A, Sliwinski M, Buschke H. The New England Journal of Medicine, 348: 2508-2516

Over a median follow-up period of 5.1 years, dementia developed in 124 subjects (Alzheimer's disease in 61 subjects, vascular dementia in 30, mixed dementia in 25, and other types of dementia in 8). Among leisure activities, reading, playing board games, playing musical instruments, and dancing were associated with a reduced risk of dementia. A one-point increment in the cognitive-activity score was significantly associated with a reduced risk of dementia (hazard ratio, 0.93 [95 percent confidence interval, 0.90 to 0.97]), but a one-point increment in the physical-activity score was not (hazard ratio, 1.00). The association with the cognitive-activity score persisted after the exclusion of the subjects with possible preclinical dementia at base line. Results were similar for Alzheimer's disease and vascular dementia. In linear mixed models, increased participation in cognitive activities at base line was associated with reduced rates of decline in memory. In conclusion: Participation in leisure activities is associated with a reduced risk of dementia, even after adjustment for base-line cognitive status and after the exclusion of subjects with possible preclinical dementia.

Journal of Geriatric Psychiatry and Neurology, 18: 134-141(2005)
Participation in novelty-seeking leisure activities and Alzheimer's disease

Fritsch T, Smyth KA, Debanne SM, Petot GJ, Friedland RP. Journal of Geriatric Psychiatry and Neurology, 18: 134-141

Using a case-control design, research collected data on 16 types of activities performed between the ages of 20-60 years. 264 subjects with AD served as controls. Participation in novelty-seeking activities (defined in this study as: learning a new skill, learning about a new subject, doings things that are challenging mentally, solving a problem, getting a new experience, taking up a hobby) had the greatest association with reduced risk of AD. In conclusion: Greater participation in novelty-seeking and exchange-of-ideas activities across life span was associated with decreased odds of developing Alzheimer's disease.