Nonpharmacologic Activity Interventions to Prevent Alzheimer’s Disease

C H A P T E R

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Nonpharmacologic Activity Interventions to Prevent Alzheimer’s Disease M.C. Carlson O U T L I N E Overview

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Cognitive Training

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Physical Exercise and Activity

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Neurobiological Targets of Benefit: the Prefrontal Cortex and Hippocampus 591 Effects of Physical Activity on Age-Related Neurobiological Targets 592 Lifestyle Activity, Environmental Enrichment, and Neurocognitive Health

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Addressing the Challenges of Sustaining Physical Activity in Later Life 594 Yoga and Mindfulness Activities

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Increasing Cognitive and Physical Activity in Later Life Through Social Engagement: Multimodal Interventions

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Measuring Activity in Daily Life and at Night

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Conclusions

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References

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OVERVIEW One-third of cases of Alzheimer’s disease (AD) worldwide are estimated to be attributable to modifiable risk factors and behaviors that include low education, physical inactivity, smoking, depression, midlife hypertension, obesity, and diabetes (Norton et al., 2014). In the absence of known effective treatments to cure or delay AD progression once diagnosed,

Developing Therapeutics for Alzheimer’s Disease. http://dx.doi.org/10.1016/B978-0-12-802173-6.00022-8 Copyright © 2016 Elsevier Inc. All rights reserved.

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public health efforts have shifted to dementia prevention in cognitively healthy adults and those at elevated cognitive risk (World Health Organization, 2012). In Apr. 2015, the Institute of Medicine (IOM) issued a detailed report, Cognitive Aging: Progress in Understanding and Opportunities for Action (Blazer et al., 2015). This report recommended numerous activities to promote cognitive health that centered primarily around being physically, intellectually, and socially engaged, and reducing and managing cardiovascular disease risk factors (including hypertension, diabetes, and smoking). This chapter focuses on the growing number of activity-based interventions aimed at delaying cognitive decline, cognitive impairment, and AD, the most common form of dementia. It briefly summarizes the results of targeted cognitive training and physical exercise interventions, and then moves to the increasing number of multimodal lifestyle activity interventions that target multiple risk factors and neurobiological pathways to cognitive impairment and dementia, and highlights the utility of wearable technology in advancing the field toward novel intervention targets, including sleep behavior.

COGNITIVE TRAINING Most commercial and experimental cognitive training (or, as popularly coined, “brain” training) programs are based on the premise that practicing one or more tasks leads to improved performance on other, untrained abilities. With practice, players generally become faster and more accurate at performing the trained tasks. However, with one exception (Smith et al., 2009), training on these games does not reliably lead to transfer of training or boosts in other untrained cognitive abilities (near transfer) or to improved function in real-life daily functions, such as driving, meal preparation, or financial management (far transfer) (Baniqued et al., 2013), and expectations of benefit may lead to placebo effects (Boot et al., 2013b). The largest randomized, controlled trial to evaluate whether cognitive training improved other cognitive abilities and independent functions in older adults was the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) trial, which randomly assigned participants to one of four training conditions: memory, reasoning, speed of processing, or a no-contact control group (Tennstedt and Unverzagt, 2013). Intervention groups received 10 training sessions over 3 months. Immediately after training, participants showed significant improvements on the tasks that they trained on, and these improvements were maintained, with the exception of memory, 10 years later (Rebok et al., 2014). However, the researchers did not observe transfer to other cognitive abilities or to self-reported daily functioning 1 and 2 years after training. By 10 years posttraining, more than 60% of those in the training arms reported less difficulty performing instrumental activities of daily living (IADLs) than nontrained participants (49%), and the speed-of-processing and reasoning groups were involved in fewer at-fault automobile crashes. Researchers attributed these modest and delayed effects to the need to observe age-related decline in perceived function in order to reveal transfer effects. Nonetheless, there is little available evidence yet suggesting that the commercially popular Lumosity, Nintendo Brain Age, and a host of related cognitive games lead to reliable and significant cognitive benefits, and none has yet demonstrated benefits in lowering risk for





Neurobiological targets of benefit: the prefrontal cortex and hippocampus

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AD. Furthermore, adherence remains a concern. One recent study in healthy older adults found that computer game-based training resulted in no cognitive benefit, due to poor adherence (Boot et al., 2013a). Thus, while these games offer benefits in being easily scalable, low-cost, self-paced, and tailored to one’s level of ability (Kueider et al., 2012), they may not be sustainable as stand-alone tools without incentives to play and, comparatively, they may not offer the same level of cognitive benefit as engaging in cognitively stimulating lifestyle activities, as exemplified by quilting and digital photography (Park et al., 2014), teambased problem-solving games (Stine-Morrow et al., 2008, 2014), and volunteering (Carlson et al., 2008a, 2009a, 2015), to be summarized later in the section on multimodal interventions.

PHYSICAL EXERCISE AND ACTIVITY Physical activity is typically categorized as leisure or lifestyle activity (eg, walking, gardening) and exercise (brisk walking, running, swimming) (Caspersen et al., 1985; Caspersen and Fulton 2008; Howley, 2001). The relationship between physical activity and risk for dementia has been equivocal in epidemiologic studies. Studies comparing those who report higher versus lower daily and weekly physical activity show a reduced risk of incident AD among the more active participants (Yoshitake et al., 1995; Abbott et al., 2004; Podewils et al., 2005; Larson et al., 2006). Self-reported physical activity, however, was not protective of dementia among a sample of religious clergy (Wilson et al., 2002) or among communitydwelling older adults (Scarmeas et al., 2001; Verghese et al., 2003). More recently, when one of these studies used objective measures of physical activity, the researchers observed that higher levels of physical activity were protective against risk for AD (Buchman et al., 2012). Advances in objective measurement of daily physical activity have further reinforced its cognitive benefits (Hillman et al., 2008). A metaanalysis of randomized, controlled trials examining the effect of aerobic training (brisk walking, jogging, and biking) on cognition among nondemented and those with mild cognitive impairment (MCI) suggest modest benefits (Smith et al., 2010). Aerobic exercise training plus strength training produced modest improvements in processing speed, executive function, and memory, with benefits being greatest for those with MCI. Similarly, lowintensity household activities and exercise of moderate to vigorous intensity were associated with improved executive function (Bixby et al., 2007). The effect of physical activity on executive function was additionally observed in adults with MCI (Scherder et al., 2005) and AD (Palleschi et al., 1996). Additionally, two large randomized trials reported improved cognitive function in older adults with MCI (Lautenschlager et al., 2008; Baker et al., 2010).

NEUROBIOLOGICAL TARGETS OF BENEFIT: THE PREFRONTAL CORTEX AND HIPPOCAMPUS Physical exercise and activity appear to benefit the neural networks most vulnerable with aging, the prefrontal cortex (PFC), the brain’s planning or executive center, and the hippocampus, a plastic region important to spatial navigation and memory formation. The PFC



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network helps us with executive processes involved in the initiation, planning, coordination, and sequencing of actions toward a goal. PFC maturation is not complete until one’s early 20s (Gogtay et al., 2004; Garon et al., 2008) and is also more vulnerable than other brain regions with increasing age, as studies show that loss of brain volume is greater in the PFC than in posterior areas of the cortex and that declines in executive functions increase with age (Buckner, 2004; Hedden and Gabrielli, 2004; Raz et al., 1998; West, 1996; Head et al., 2004) and are also impaired in the early stages of AD (Albert et al., 2001; Buckner, 2004). In community-dwelling older adults, I and my coworkers have further found that executive function declines 3 years earlier than memory and that higher cardiovascular risk may exacerbate age-related functional changes in PFC and executive task performance (Chuang et al., 2014), a finding consistent with that observed by others using behavioral (Elias et al., 2004; Laughlin et al., 2011) and structural MRI (Raz et al., 2003). The second neurobiologic system vulnerable to aging comprises the medial temporal lobes, which includes the hippocampus, the region functionally linked to spatial navigation and memory, and the region showing the most precipitous age-related decline (Buckner, 2004; Raz, 2000). This region is further implicated in risk for dementia (Killiany et al., 2002; Du et al., 2006; Raz et al., 2004; Raz and Rodrigue, 2006). The hippocampus provides a structural and functional juncture between memory and spatial navigation by linking movement through physical activity with the consolidation and updating of information learned as one moves from location to location.

EFFECTS OF PHYSICAL ACTIVITY ON AGE-RELATED NEUROBIOLOGICAL TARGETS Animal and human research shows that physical activity likely mediates benefits in neurocognitive health through multiple neurotrophic and cardiovascular pathways (van Praag et al., 1999a,b; Vaynman et al., 2004; Ferris et al., 2007; Voss et al., 2014), including neurogenesis in the hippocampus (Erickson et al., 2011), upregulation of brain-derived neurotrophic factor (BDNF) and VEG-F (Lee et al., 2001), reduction of obesity (Mitchell et al., 2003) and insulin levels (Katzel et al., 1995), increased carotid wall thickness (Folsom et al., 1994), and cerebral blood flow (Pereira et al., 2007). Physical fitness and walking activity have been shown to directly influence the functional and structural properties of the PFC and hippocampus. In a randomized, controlled trial of aerobic walking exercise, Kramer and coworkers observed neurocognitive benefits in the efficiency of executive function and brain activity in the PFC (Colcombe et al., 2004, 2006). The same effects were not observed in a toning and stretching control group. Cross-sectional and longitudinal studies have also reported an inverse association between self-reported physical activity and moderation of age-related decreases in mediotemporal volume (Bugg and Head, 2011), and with mitigated rates of decline in hippocampal volume over 9–13 years (Erickson et al., 2010). Greater cardiorespiratory fitness levels have been cross-sectionally associated with greater hippocampal volume in both children (Chaddock et al., 2009) and healthy older adults (Erickson et al., 2009). Erickson et al. (2011) found that a moderate-intensity walking for exercise intervention over 1 year increased hippocampal volume by 2%. We have extended this finding to the study of low-intensity





Lifestyle activity, environmental enrichment, and neurocognitive health

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(nonexercise) walking activity in daily life, and hippocampal volume in mostly sedentary older adults. Our cross-sectional findings showed that higher levels of daily walking were associated with larger hippocampal volume, suggesting that even modest increases in lowintensity walking activity in daily life may yield neurocognitive benefits. Given that older adults who participate in physical activity interventions often revert back to their baseline, sedentary state (van der Bij et al., 2002), these data suggest that activity in day-to-day life may represent a target for intervention to delay and mitigate memory declines that may lead to dementia (Carlson et al., 2009b).

LIFESTYLE ACTIVITY, ENVIRONMENTAL ENRICHMENT, AND NEUROCOGNITIVE HEALTH Evidence from animal models of environmental enrichment summarized by Kempermann et al. (2010) provides more detailed mechanistic support for the premise that physical activity may be necessary but not sufficient to sustain neurogenesis in adult animals. They summarize rigorously controlled environmental enrichment paradigms in animals spanning more than a decade and conclude that, while exercise helps promote and regulate adult neurogenesis (generation of new neurons), exposure to environmental complexity and novelty recruits these new cells for functional integration with existing neurons. Enriched environments are designed to provide novel challenges that combine curiosity and play with modest levels of physical activity (Sale et al., 2009). Functional activation of new neurons in these enriched environments occurs in older animals and exceeds that of younger animals (Kempermann et al., 1998, 2002). In humans, cognitive enrichment through mid- and late-life activity appears to have beneficial effects on cognition (Raz, 2000; Blumenthal et al., 1989; Gunning-Dixon and Raz, 2003; Arbuckle et al., 1998; Baltes and Willis, 1982; Carlson et al., 2012), risk for neurodegenerative disorders (Gribbin et al., 1980; Pushkar et al., 1997, 1999; Schooler et al., 1999; Scarmeas et al., 2001; Stern et al., 1999; Wang et al., 2002), neuronal architecture (Wilson et al., 1999, 2002; Gould et al., 1999; Greenough et al., 1999; van Praag et al., 1999a,b), and cerebral perfusion (Rogers et al., 1990). The nature of cognitively enriching activity may take numerous forms in everyday life. We have observed benefits in rates of cognitive aging emerge from engaging in a variety of activities (Podewils et al., 2005), and that among male twin pairs, the male participating in a greater range of cognitively and socially engaging activities in midlife had reduced risk for AD and dementia 28 years later in a finding magnified among those at elevated genetic risk for the disease (Carlson et al., 2008a). Protective effects were most robust in monozygotic (identical) twin pairs, where genetic and early-life influences were most tightly controlled. These activities might be indicative of an enriched environment, which may provide cognitive benefits through the mechanism postulated by Kempermann et al. (2010) and elaborated elsewhere (Carlson and Varma, 2015). While there is now ample evidence that physically, cognitively, and socially enriching environments promote the emergence of new neurons in animals throughout life (Kempermann et al., 2006), little of this work has been directly translated to human physical activity interventions targeting neurocognitive health and risk for AD.



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ADDRESSING THE CHALLENGES OF SUSTAINING PHYSICAL ACTIVITY IN LATER LIFE A paradox of aging is that older adults represent the group with the most to gain from regular physical activity because of its beneficial effects on PFC, executive function, cardiovascular and diabetic risk, and a host of other health-related outcomes beyond the scope of this chapter. Unfortunately, they are also the subset of the population with the highest rates of inactivity (van der Bij et al., 2002). Exercise programs have been difficult to promote adherence to in any long-term, large-scale way (Pate et al., 1995) and have primarily been conducted in those with higher socioeconomic status (SES) (Katula et al., 2007; Stewart et al., 2001). Among those with lower SES, neighborhood factors often restrict opportunities for regular exercise (Moore et al., 2008). Lifestyle activity interventions that target changes in low-intensity physical activity may have the greatest potential for sustainability beyond the intervention period, particularly in older adults who have a high burden of chronic diseases, who are overweight, and who have osteoarthritis, which may make moderately vigorous activities painful.

YOGA AND MINDFULNESS ACTIVITIES Derived from Eastern contemplative traditions, mindfulness practices—which include yoga and meditation—involve attending to the present moment in a sustained and receptive fashion (Brown and Ryan, 2003). Yoga is a form of mindfulness practice that involves breathing techniques and movement sequences that train balance, strength, and flexibility. Mindfulness practices have been associated with benefits to multiple components of cognition, including attention, memory, and executive functions (Gard et al., 2014; Jha et al., 2007a,b; Tang et al., 2007; Zeidan et al., 2010; Chiesa et al., 2011; Bishop et al., 2004), and to brain function and structure relevant to cognition and motor control (Allen et al., 2012; Brefczynski-Lewis et al., 2007; Holzel et al., 2007, 2011; Lazar et al., 2000, 2005; Davidson and McEwen, 2012). Randomized trials of similar meditation-based forms of physical activity, including Tai chi and Qigong, have also shown cognitive benefits (Lam et al., 2011; Taylor-Piliae et al., 2010). A review of studies comparing the effects of yoga and traditional physical exercise found that yoga may be equally or more effective as exercise for improving various health outcomes (Ross and Thomas, 2010). In a metaanalysis of randomized clinical trials, the benefits of yoga for older adults were shown to exceed those of conventional physical activity interventions (Patel et al., 2011). However, yoga and mindfulness interventions have been evaluated primarily in those with higher SES. Among those with lower SES, additional infrastructure may be necessary to help overcome economic and neighborhood barriers to engaging in these activities (Frank et al., 2010; Saelens et al., 2003; Leslie et al., 2007; Randall and Baetz, 2001; Cole et al., 2006). Physical activity interventions that can circumvent these challenges through the proximal placement of yoga in community centers have the potential for long-term impact in large groups, particularly among those at elevated sociodemographic risk for AD (Frank et al., 2010; Cunningham and Michael, 2004; Balfour and Kaplan, 2002).





INCREASING COGNITIVE AND PHYSICAL ACTIVITY IN LATER LIFE THROUGH SOCIAL ENGAGEMENT

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INCREASING COGNITIVE AND PHYSICAL ACTIVITY IN LATER LIFE THROUGH SOCIAL ENGAGEMENT: MULTIMODAL INTERVENTIONS A growing body of evidence in middle-aged and older adults suggests that low social activity is associated with increased risk for AD (Kondo et al., 1994) and that midlife (Saczynski et al., 2006) and late-life social engagement is associated with better cognitive and physical health and greater longevity (Bassuk et al., 1999; Zunzunegui et al., 2003; Taylor et al., 2000) (for review, see Fratiglioni et al., 2004). Both social integration and social activity predict better functioning and reduced risk for declines in cognitive functioning (House et al., 1988; Seeman et al., 1987, 1993, 1995; La Greca et al., 1995; Wang et al., 2002; Barnes et al., 2004; Karp et al., 2006). Ironically, transitions with increasing age, such as retirement and resulting loss of routine contact with coworkers, as well as increasing tendencies for adult offspring to live remotely, make older adults a population at high risk for decreasing levels of social integration and interaction. As a result, opportunities for social activity and engagement become more restricted and sporadic (Unger et al., 1997; Everard, 1999; Everard et al., 2000). Multimodal interventions that combine multiple activity pathways are increasing rapidly. They have typically combined physical exercise and cognitive training to explore whether benefits exceed those for either alone. The Mental Activity and eXercise (MAX) trial recruited inactive older adults with cognitive complaints to a 3-month intervention combining cognitive training with an aerobic exercise program. The study observed similar improvements in cognitive function in the combined intervention group compared to active cognitive control (DVD viewing) and exercise control (stretching and toning) groups (Barnes et al., 2013). These two control groups were used to account for the effects of factors such as interaction with a computer and social interaction during a group exercise class. The multicomponent (diet, exercise, cognitive training, vascular risk monitoring) Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) proof-of-concept trial found modest but significant intervention-related benefits over 2 years on a composite measure of cognition and specifically on tests of executive function and processing speed (Ngandu et al., 2015). Pilot results from the ThinkingFit intervention suggest potential cognitive benefits for participants with MCI (Dannhauser et al., 2014). Other activity-based trials, including the Synapse Project of digital photography and quilting, the Senior Odyssey program, and an iPad training study, have shown memory benefits from combined social and cognitive enrichment interventions (Chan et al., 2014; Park et al., 2013; Stine-Morrow et al., 2007). Of note, the Synapse Project trial included a receptive social control group that yielded limited cognitive benefits relative to the productive and social quilting and photography activities. Collectively, these findings suggest that engagement in cognitively and socially challenging activities embedded within daily life can enhance multiple domains of cognition. Experience Corps (EC) represents just such a novel approach, offering a scalable opportunity for increasing physical, cognitive, and social activity in daily life. EC is a community-based health promotion program embedded within a high-intensity volunteer service program that has operated nationally for more than 17 years (Freedman and Fried, 1999) and, since 2011, under the direction of the American Association of Retired Persons (AARP). The goal of this program is to improve the academic performance of young children in underserved urban areas by using older adults’ time, skills, and wisdom. In the Baltimore EC program, retired



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adults volunteer in teams of 10–15 in neighborhood elementary schools as mentors of children in kindergarten through grade 3 for 15 h a week over 1–2 academic years (Freedman and Fried, 1999; Fried et al., 2004, 2013; Glass et al., 2004; Parisi et al., 2009; Rebok et al., 2011). The EC model provides a real-world example of how increases in these activities lead to self-reported increases in physical activity (Fried et al., 2004; Tan et al., 2006) and cognitive activity (Fried et al., 2004), cognitive health (Carlson et al., 2008b), and improved brain activity in regions that support executive attention (Carlson et al., 2009a). A formal large-scale trial evaluation initiated in 2006, the Baltimore Experience Corps Trial (BECT), was among the first interventions to explore the neurocognitive benefits of simultaneously increasing physical and cognitive activity through purposeful social engagement over 2 academic years of service (Fried et al., 2004, 2013). A nested neuroimaging trial within the BECT showed interventionspecific increases in objectively measured physical activity among female volunteers (Varma et al., 2014) and dose-dependent benefits to hippocampal and total cortical volumes (Carlson et al., 2015). These findings regarding EC’s benefits highlight the potential of real-world, community-based interventions for simultaneously raising low levels of physical activity and improving neurocognitive health in older adults at elevated risk for AD by virtue of low education and high cardiovascular risk (Carlson et al., 2009a).

MEASURING ACTIVITY IN DAILY LIFE AND AT NIGHT Targeting increases in low-intensity, daily physical activity warrant improved methods for assessment. Recent advances in wearable computing open up new frontiers in neurocognitive intervention research. Digital technologies are becoming a regular part of daily life and provide us with a low-cost opportunity to transform standard practices in the assessment of cognitive, physical, and social activity. High-dimensional information obtained through wearable devices allows us to advance beyond self-report to provide finer spatial and temporal granularity with which to capture previously undetected changes in diurnal patterns that may increase lifestyle activity (Carlson MC, Varma VR, Adam A, Crainiceanu C, Zipunnikov V: Linking community activity to cognitive and brain health in older adults using wearable technology. Unpublished observation). Lifestyle activity among EC volunteers and those participating in other activity interventions, described previously, may have changed in modest but sustainable ways (Varma et al., in press). Use of accelerometers, GPS, and other wearable technology will enable us to circumvent self-report to directly evaluate how even modest changes in the dose, duration, and location of physical activity (eg, in complex community spaces vs at home) may be related to neurocognitive health and risk for AD. Incorporation of wearable technology will also allow us to better evaluate nighttime activity or sleep patterns. At least 50% of older adults report insomnia symptoms (ie, difficulty falling to sleep or staying asleep) (Foley et al., 1995; Ohayon, 2002), and, in recent years, self-reported sleep disturbance, poorer sleep quality, and difficulty falling or staying asleep have been associated with poorer cognition, cognitive decline (Nebes et al., 2009; Tworoger et al., 2006; Cricco et al., 2001; Jelicic et al., 2002), and greater amyloid deposition (Spira et al., 2013). Studies using objective, wrist-worn measures of sleep disruptions (movement) (Ancoli-Israel et al., 2003) have found that shorter sleep duration, longer sleep onset latency, greater sleep fragmentation, and less efficient sleep were associated



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with poorer cognition (Blackwell et al., 2006, 2014), greater amyloid burden (Ju et al., 2013), worse physical function (Spira et al., 2010), and functional decline (Spira et al., 2012). As a result, assessment of sleep patterns warrants investigation as a mechanism through which activity-based interventions may exert impacts on cognitive impairment, neuropathology, and AD risk.

CONCLUSIONS Data summarized here suggest that activity-based interventions seeking to slow cognitive declines and delay dementia onset are on the rise and hold promise in ongoing follow-up. Physical activity, yoga, and low-intensity physical activity embedded within one’s complex social environment may affect cognitive and brain health in multiple ways that impact directly or indirectly the neuropathology and clinical symptoms of AD. Recent intervention efforts are increasingly targeting individuals in the community who may not self-identify risk but who are at elevated risk for AD based on poor cognitive function (eg, MCI) or based on the presence of known behavioral risk factors (eg, inactivity, low education). Many of these programs are scalable through existing clinical settings and community infrastructure, including schools, retirement centers, religious centers, YMCAs, and other public and private nonprofit organizations. At the same time, much remains to be learned about the specific physical and lifestyle activities that contribute to cognitive health or offer resilience to pathology, and the limits of their effectiveness. Questions that remain to be addressed in this developing field are not unlike those related to pharmacological studies, and include exposure or dosing (intensity/strength, duration), adherence, and sustainability of gains postexposure. A critical objective for studies going forward will be to explore the interactive, and potentially synergistic, effects of multimodal interventions incorporated into daily life using real-time wearable technologies that increase measurement precision.

References Abbott RD, White LR, Ross GW, Masaki KH, Curb JD, Petrovitch H: Walking and dementia in physically capable elderly men, J Am Med Assoc 292:1447–1453, 2004. Albert MS, Moss MB, Tanzi R, Jones K: Preclinical prediction of AD using neuropsychological tests, J Int Neuropsychol Soc 7:631–639, 2001. Allen M, Dietz M, Blair KS, Van Beek M, Rees G, Vestergaard-Poulsen P, Lutz A, Roepstorff A: Cognitive-affective neural plasticity following active-controlled mindfulness intervention, J Neurosci 32:15601–15610, 2012. Ancoli-Israel S, Cole R, Alessi C, Chambers M, Moorcroft W, Pollak CP: The role of actigraphy in the study of sleep and circadian rhythms, Sleep 26:342–392, 2003. Arbuckle TY, Maag U, Pushkar D, Chaikelson JS: Individual differences in trajectory of intellectual development over 45 years of adulthood, Psychol Aging 13:663–675, 1998. Baker LD, Frank LL, Foster-Schubert K, Green PS, Wilkinson CW, McTiernan A, Plymate SR, Fishel MA, Watson GS, Cholerton BA, Duncan GE, Mehta PD, Craft S: Effects of aerobic exercise on mild cognitive impairment: a controlled trial, Arch Neurol 67:71–79, 2010. Balfour JL, Kaplan GA: Neighborhood environment and loss of physical function in older adults: evidence from the Alameda County Study, Am J Epidemiol 155:507–515, 2002. Baltes PB, Willis SL: Plasticity and enhancement of intellectual functioning in old age: Penn State’s Adult Development and Enrichment Project (ADEPT). In Craik FIM, Trehub SE, editors: Aging and cognitive processes, New York, 1982, Plenum Press.



598

22.  Nonpharmacologic Activity Interventions to Prevent Alzheimer’s Disease

Baniqued PL, Kranz MB, Voss MW, Lee H, Cosman JD, Severson J, Kramer AF: Cognitive training with casual video games: points to consider, Front Psychol 4:1010, 2013. Barnes LL, Mendes De Leon CF, Wilson RS, Bienias JL, Evans DA: Social resources and cognitive decline in a population of older African Americans and whites, Neurology 63:2322–2326, 2004. Barnes DE, Santos-Modesitt W, Poelke G, Kramer AF, Castro C, Middleton LE, Yaffe K: The Mental Activity and eXercise (MAX) trial: a randomized controlled trial to enhance cognitive function in older adults, JAMA Intern Med 173:797–804, 2013. Bassuk SS, Glass TA, Berkman LF: Social disengagement and incident cognitive decline in community-dwelling elderly persons, Ann Intern Med 131:165–173, 1999. Bishop S, Lau M, Shapiro S, Carlson L, Anderson N, Carmody J, Segal Z, Speca M, Velting D, Devins G: Mindfulness: a proposed operational definition, Clin Psychol 11:230–241, 2004. Bixby WR, Spalding TW, Haufler AJ, Deeny SP, Mahlow PT, Zimmerman JB, Hatfield BD: The unique relation of physical activity to executive function in older men and women, Med Sci Sports Exerc 39:1408–1416, 2007. Blackwell T, Yaffe K, Ancoli-Israel S, Schneider JL, Cauley JA, Hillier TA, Fink HA, Stone KL: Poor sleep is associated with impaired cognitive function in older women: the study of osteoporotic fractures, J Gerontol A 61:405–410, 2006. Blackwell T, Yaffe K, Laffan A, Ancoli-Israel S, Redline S, Ensrud KE, Song Y, Stone KL: Associations of objectively and subjectively measured sleep quality with subsequent cognitive decline in older community-dwelling men: the MrOS sleep study, Sleep 37:655–663, 2014. Blazer D, Yaffe K, Liverman C: Cognitive aging: progress in understanding and opportunities for action, Washington, DC, 2015, National Academies Press. Blumenthal JA, Emery CF, Madden DJ, George LK, Coleman RE, Riddle MW, McKee DC, Reasoner J, Williams RS: Cardiovascular and behavorial effects of aerobic exercise training in healthy older men and women, J Gerontol 44:M147–M157, 1989. Boot WR, Champion M, Blakely DP, Wright T, Souders DJ, Charness N: Video games as a means to reduce age-related cognitive decline: attitudes, compliance, and effectiveness, Front Psychol 4:1–9, 2013a. Boot WR, Simons DJ, Stothart C, Stutts C: The pervasive problem with placebos in psychology why active control groups are not sufficient to rule out placebo effects, Perspect Psychol Sci 8:445–454, 2013b. Brefczynski-Lewis JA, Lutz A, Schaefer HS, Levinson DB, Davidson RJ: Neural correlates of attentional expertise in long-term meditation practitioners, Proc Natl Acad Sci USA 104:11483–11488, 2007. Brown K, Ryan R: The benefits of being present: mindfulness and its role in psychological well-being, J Pers Soc Psychol 84:822–848, 2003. Buchman AS, Boyle PA, Yu L, Shah RC, Wilson RS, Bennett DA: Total daily physical activity and the risk of AD and cognitive decline in older adults, Neurology 78:1323–1329, 2012. Buckner RL: Memory and executive function in aging and AD: multiple factors that cause decline and reserve factors that compensate, Neuron 44:195–208, 2004. Bugg JM, Head D: Exercise moderates age-related atrophy of the medial temporal lobe, Neurobiol Aging 32:506–514, 2011. Carlson MC, Varma VR: Activity and neurocognitive health in older adults. Neuropsychology of cardiovascular disease, ed 2, New York, 2015, Psychology Press, pp 79–108. Carlson MC, Helms MJ, Steffens DC, Burke JR, Potter GG, Plassman BL: Midlife activity predicts risk of dementia in older male twin pairs, Alzheimers Dement 4:324–331, 2008a. Carlson MC, Saczynski JS, Rebok GW, Seeman T, Glass TA, McGill S, Tielsch J, Frick KD, Hill J, Fried LP: Exploring the effects of an “everyday” activity program on executive function and memory in older adults: Experience Corps, Gerontologist 48:793–801, 2008b. Carlson MC, Erickson KI, Kramer AF, Voss MW, Bolea N, Mielke M, McGill S, Rebok GW, Seeman T, Fried LP: Evidence for neurocognitive plasticity in at-risk older adults: the Experience Corps program, J Gerontol A 64:1275– 1282, 2009a. Carlson M, Xue QL, Zhou J, Fried LP: Executive decline and dysfunction precedes declines in memory: the Women’s Health and Aging Study II, J Gerontol A 64:110–117, 2009b. Carlson MC, Parisi JM, Xia J, Xue Q-L, Rebok GW, Bandeen-Roche K, Fried LP: Lifestyle activities and memory: variety may be the spice of life: the Women’s Health and Aging Study II, J Int Neuropsychol Soc 18:286–294, 2012. Carlson MC, Kuo JH, Chuang YF, Varma V, Harris G, Albert M, Erickson KI, Kramer AF, Parisi JM, Xue QL, Tan E, Tanner EK, Gross A, Seeman TE, Gruenewald T, McGill S, Rebok GW, Fried LP: Impact of the Baltimore Experience Corps trial on cortical and hippocampal volumes, Alzheimers Dement 11:1340–1348, 2015. 

REFERENCES 599

Caspersen CJ, Powell KE, Christenson GM: Physical activity, exercise, and physical fitness: definitions and distinctions for health-related research, Public Health Rep 100:126–131, 1985. Caspersen CJ, Fulton JE: Epidemiology of walking and type 2 diabetes, Med Sci Sports Exerc 40(7 Suppl):S519–S528, 2008. Chaddock L, Erickson KI, Prakash RS, Kim JS, Voss MW, Vanpatter M, Pontifex MB, Raine LB, Konkel A, Hillman CH, Cohen NJ, Kramer AF: A neuroimaging investigation of the association between aerobic fitness, hippocampal volume, and memory performance in preadolescent children, Brain Res 1358:172–183, 2009. Chan MY, Haber S, Drew LM, Park DC: Training older adults to use tablet computers: does it enhance cognitive function? Gerontologist 54:1–11, 2014. Chiesa A, Calati R, Seretti A: Does mindfulness training improve cognitive abilities? A systematic review of neuropsychological findings, Clin Psychol Rev 31:449–464, 2011. Chuang YF, Eldreth D, Erickson KI, Varma V, Harris G, Fried LP, Rebok GW, Tanner EK, Carlson MC: Cardiovascular risks and brain function: a functional magnetic resonance imaging study of executive function in older adults, Neurobiol Aging 35:1396–1403, 2014. Colcombe SJ, Kramer AF, Erickson KI, Scalf P, McAuley E, Cohen NJ, Webb A, Jerome GJ, Marquez DX, Elavsky S: Cardiovascular fitness, cortical plasticity, and aging, Proc Natl Acad Sci USA 101:3316–3321, 2004. Colcombe SJ, Erickson KI, Scalf PE, Kim JS, Prakash R, McAuley E, Elavsky S, Marquez DX, Hu L, Kramer AF: Aerobic exercise training reduces brain tissue loss in aging humans, J Gerontol A 61:1166–1170, 2006. Cole R, Leslie E, Bauman A, Donald M, Owen N: Socio-demographic variations in walking for transport and for recreation or exercise among adult Australians, J Phys Activity Health 3:164, 2006. Cricco M, Simonsick EM, Foley DJ: The impact of insomnia on cognitive functioning in older adults, J Am Geriatr Soc 49:1185–1189, 2001. Cunningham GO, Michael YL: Concepts guiding the study of the impact of the built environment on physical activity for older adults: a review of the literature, Am J Health Promot 18:435–443, 2004. Dannhauser TM, Cleverley M, Whitfield TJ, Fletcher BC, Stevens T, Walker Z: A complex multimodal activity intervention to reduce the risk of dementia in mild cognitive impairment—ThinkingFit: pilot and feasibility study for a randomized controlled trial, BMC Psychiatr 14:129, 2014. Davidson RJ, McEwen BS: Social influences on neuroplasticity: stress and interventions to promote well-being, Nat Neurosci 15:689–695, 2012. Du AT, Schuff N, Chao LL, Kornak J, Jagust WJ, Kramer JH, Reed BR, Miller BL, Norman D, Chui HC, Weiner MW: Age effects on atrophy rates of entorhinal cortex and hippocampus, Neurobiol Aging 27:733–740, 2006. Elias P, Elias M, Robbins M, Budge M: Blood pressure-related cognitive decline: does age make a difference? Hypertension 44:631–636, 2004. Erickson KI, Prakash RS, Voss MW, Chaddock L, Hu L, Morris KS, White SM, Wojcicki TR, McAuley E, Kramer AF: Aerobic fitness is associated with hippocampal volume in elderly humans, Hippocampus 19:1030–1039, 2009. Erickson KI, Raji CA, Lopez OL, Becker JT, Rosano C, Newman AB, Gach HM, Thompson PM, Ho AJ, Kuller LH: Physical activity predicts gray matter volume in late adulthood: the Cardiovascular Health Study, Neurology 75:1415–1422, 2010. Erickson KI, Voss MW, Prakash RS, Basak C, Szabo A, Chaddock L, Kim JS, Heo S, Alves H, White SM, Wojcicki TR, Mailey E, Vieira VJ, Martin SA, Pence BD, Woods JA, McAuley E, Kramer AF: Exercise training increases size of hippocampus and improves memory, Proc Natl Acad Sci USA 108:3017–3022, 2011. Everard KM: The relationship between reasons for activity and older adult well-being, J Appl Gerontol 18:325–340, 1999. Everard KM, Lach HW, Fisher EB, Baum MC: Relationship of activity and social support to the functional health of older adults, J Gerontol B 55:S208–S212, 2000. Ferris LT, Williams JS, Shen CL: The effect of acute exercise on serum brain-derived neurotrophic factor levels and cognitive function, Med Sci Sports Exerc 39:728–734, 2007. Foley DJ, Monjan AA, Brown SL, Simonsick EM, Wallace RB, Blazer DG: Sleep complaints among elderly persons: an epidemiologic study of three communities, Sleep Med Rev 18:425–432, 1995. Folsom AR, Eckfeldt JH, Weitzman S, Ma J, Chambless LE, Barnes RW, Cram KB, Hutchinson RG: Relation of carotid artery wall thickness to diabetes mellitus, fasting glucose and insulin, body size, and physical activity: Atherosclerosis Risk in Communities (ARIC) Study Investigators, Stroke 25:66–73, 1994. Frank L, Kerr J, Rosenberg D, King A: Healthy aging and where you live: community design relationships with physical activity and body weight in older Americans, J Phys Act Health 7(Suppl 1):S82–S90, 2010. 

600

22.  Nonpharmacologic Activity Interventions to Prevent Alzheimer’s Disease

Fratiglioni L, Paillard-Borg S, Winblad B: An active and socially integrated lifestyle in late life might protect against dementia, Lancet Neurol 3:343–353, 2004. Freedman M, Fried L: Launching Experience Corps: findings from a two-year pilot project mobilizing older Americans to help inner-city elementary schools, Oakland, CA, 1999, Civic Ventures. Fried LP, Carlson MC, Freedman M, Frick KD, Glass TA, Hill J, McGill S, Rebok GW, Seeman T, Tielsch J, Wasik BA, Zeger S: A social model for health promotion for an aging population: initial evidence on the Experience Corps model, J Urban Health 81:64–78, 2004. Fried LP, Carlson MC, McGill S, Seeman T, Xue QL, Frick K, Tan E, Tanner EK, Barron J, Frangakis C, Piferi R, Martinez I, Gruenewald T, Martin BK, Berry-Vaughn L, Stewart J, Dickersin K, Willging PR, Rebok GW: Experience Corps: a dual trial to promote the health of older adults and children’s academic success, Contemp Clin Trials 36:1–13, 2013. Gard T, Holzel BK, Lazar SW: The potential effects of meditation on age-related cognitive decline: a systematic review, Ann NY Acad Sci 1307:89–103, 2014. Garon N, Bryson SE, Smith IM: Executive function in preschoolers: a review using an integrative framework, Psychol Bull 134:31–60, 2008. Glass TA, Freedman M, Carlson MC, Hill J, Frick KD, Ialongo N, McGill S, Rebok GW, Seeman T, Tielsch JM, Wasik BA, Zeger S, Fried LP: Experience Corps: design of an intergenerational program to boost social capital and promote the health of an aging society, J Urban Health 81:94–105, 2004. Gogtay N, Sporn A, Clasen LS, Nugent TF III, Greenstein D, Nicolson R, Giedd JN, Lenane M, Gochman P, Evans A, Rapoport JL: Comparison of progressive cortical gray matter loss in childhood-onset schizophrenia with that in childhood-onset atypical psychoses, Arch Gen Psychiatr 61:17–22, 2004. Gould E, Beylin A, Tanapat P, Reeves A, Shors TJ: Learning enhances adult neurogenesis in the hippocampal formation, Nat Neurosci 2:260–265, 1999. Greenough WT, Cohen NJ, Juraska JM: New neurons in old brains: learning to survive? Nat Neurosci 2: 203–205, 1999. Gribbin K, Schaie KW, Parham IA: Complexity of life style and maintenance of intellectual abilities, J Social Issues 36:47–61, 1980. Gunning-Dixon FM, Raz N: Neuroanatomical correlates of selected executive functions in middle-aged and older adults: a prospective MRI study, Neuropsychologia 41:1929–1941, 2003. Head D, Buckner RL, Shimony JS, Williams LE, Akbudak E, Conturo TE, McAvoy M, Morris JC, Snyder AZ: Differential vulnerability of anterior white matter in nondemented aging with minimal acceleration in dementia of the Alzheimer type: evidence from diffusion tensor imaging, Cereb Cortex 14:410–423, 2004. Hedden T, Gabrielli J: Insights into the ageing mind: a view from cognitive neuroscience, Nat Rev Neurosci 5:87–96, 2004. Hillman CH, Erickson KI, Kramer AF: Be smart, exercise your heart: exercise effects on brain and cognition, Nat Rev Neurosci 9:58–65, 2008. Holzel BK, Ott U, Hempel H, Hackl A, Wolf K, Stark R, Vaitl D: Differential engagement of anterior cingulate and adjacent medial frontal cortex in adept meditators and non-meditators, Neurosci Lett 421:16–21, 2007. Holzel BK, Carmody J, Vangel M, Congleton C, Yerramsetti SM, Gard T, Lazar SW: Mindfulness practice leads to increases in regional brain gray matter density, Psychiatr Res 191:36–43, 2011. House JS, Landis KR, Umberson D: Social relationships and health, Science 241:540–545, 1988. Howley ET: Type of activity: resistance, aerobic and leisure versus occupational physical activity, Med Sci Sports Exerc 33:S364–S369, 2001 (discussion S419–S420). Jelicic M, Bosma H, Ponds RW, Van Boxtel MP, Houx PJ, Jolles J: Subjective sleep problems in later life as predictors of cognitive decline: report from the Maastricht Ageing Study (MAAS), Int J Geriatr Psychiatr 17: 73–77, 2002. Jha AP, Krompinger J, Baime MJ: Mindfulness training modifies subsystems of attention, Cogn Affect Behav Neurosci 7:109–119, 2007a. Jha AP, Stanley EA, Kiyonaga A, Wong L, Gelfand L: Examining the protective effects of mindfulness training on working memory capacity and affective experience, Emotion 10:54–64, 2007b. Ju YE, McLeland JS, Toedebusch CD, Xiong C, Fagan AM, Duntley SP, Morris JC, Holtzman DM: Sleep quality and preclinical Alzheimer disease, JAMA Neurol 70:587–593, 2013. Karp A, Paillard-Borg S, Wang HX, Silverstein M, Winblad B, Fratiglioni L: Mental, physical and social components in leisure activities equally contribute to decrease dementia risk, Dement Geriatr Cogn Disord 21:65–73, 2006.



REFERENCES 601

Katula JA, Kritchevsky SB, Guralnik JM, Glynn NW, Pruitt L, Wallace K, Walkup MP, Hsu FC, Studenski SA, Gill TM, Groessl EJ, Wallace JM, Pahor M: Lifestyle interventions and independence for elders pilot study: recruitment and baseline characteristics, J Am Geriatr Soc 55:674–683, 2007. Katzel LI, Bleecker ER, Colman EG, Rogus EM, Sorkin JD, Goldberg AP: Effects of weight loss vs aerobic exercise training on risk factors for coronary disease in healthy, obese, middle-aged and older men: a randomized controlled trial, J Am Med Assoc 274:1915–1921, 1995. Kempermann G, Kuhn HG, Gage FH: Experience-induced neurogenesis in the senescent dentate gyrus, J Neurosci 18:3206–3212, 1998. Kempermann G, Gast D, Gage FH: Neuroplasticity in old age: sustained fivefold induction of hippocampal neurogenesis by long-term environmental enrichment, Ann Neurol 52:135–143, 2002. Kempermann G, Chesler EJ, Lu L, Williams RW, Gage FH: Natural variation and genetic covariance in adult hippocampal neurogenesis, Proc Natl Acad Sci USA 103:780–785, 2006. Kempermann G, Fabel K, Ehninger D, Babu H, Leal-Galicia P, Garthe A, Wolf SA: Why and how physical activity promotes experience-induced brain plasticity, Front Neurosci 4:189, 2010. Killiany RJ, Hyman BT, Gomez-Isla T, Moss MB, Kikinis R, Jolesz F, Tanzi R, Jones K, Albert MS: MRI measures of entorhinal cortex vs hippocampus in preclinical AD, Neurology 58:1188–1196, 2002. Kondo K, Niino M, Shido K: A case-control study of Alzheimer’s disease in Japan—significance of life-styles, Dementia 5:314–326, 1994. Kueider AM, Parisi JM, Gross AL, Rebok GW: Computerized cognitive training with older adults: a systematic review, PLoS One 7:e40588, 2012. La Greca AM, Auslander WF, Greco P, Spetter D, Fisher EB Jr, Santiago JV: I get by with a little help from my family and friends: adolescents’ support for diabetes care, J Pediatr Psychol 20:449–476, 1995. Lam LC, Chau RC, Wong BM, Fung AW, Lui VW, Tam CC, Leung GT, Kwok TC, Chiu HF, Ng S, Chan WM: Interim follow-up of a randomized controlled trial comparing Chinese style mind body (tai chi) and stretching exercises on cognitive function in subjects at risk of progressive cognitive decline, Int J Geriatr Psychiatr 26:733–740, 2011. Larson EB, Wang L, Bowen JD, McCormick WC, Teri L, Crane P, Kukull W: Exercise is associated with reduced risk for incident dementia among persons 65 years of age and older, Ann Internal Med 144:73–81, 2006. Laughlin GA, McEvoy LK, Von Muhlen D, Daniels LB, Kritz-Silverstein D, Bergstrom J, Cummins K, Der-Martirosian C, Jassal SK, Barrett-Connor E: Sex differences in the association of Framingham Cardiac Risk Score with cognitive decline in community-dwelling elders without clinical heart disease, Psychosom Med 73:683–689, 2011. Lautenschlager NT, Cox KL, Flicker L, Foster JK, Van Bockxmeer FM, Xiao J, Greenop KR, Almeida OP: Effect of physical activity on cognitive function in older adults at risk for Alzheimer disease: a randomized trial, J Am Med Assoc 300:1027–1037, 2008. Lazar SW, Bush G, Gollub RL, Fricchione GL, Khalsa G, Benson H: Functional brain mapping of the relaxation response and meditation, Neuroreport 11:1581–1585, 2000. Lazar SW, Kerr CE, Wasserman RH, Gray JR, Greve DN, Treadway MT, McGarvey M, Quinn BT, Dusek JA, Benson H, Rauch SL, Moore CI, Fischl B: Meditation experience is associated with increased cortical thickness, Neuroreport 16:1893–1897, 2005. Lee R, Kermani P, Teng KK, Hempstead BL: Regulation of cell survival by secreted proneurotrophins, Science 294:1945–1948, 2001. Leslie E, Coffee N, Frank L, Owen N, Bauman A, Hugo G: Walkability of local communities: using geographic information systems to objectively assess relevant environmental attributes, Health Place 13:111–122, 2007. Mitchell D, Haan MN, Steinberg FM, Visser M: Body composition in the elderly: the influence of nutritional factors and physical activity, J Nutr Health Aging 7:130–139, 2003. Moore HJ, Ells LJ, McLure SA, Crooks S, Cumbor D, Summerbell CD, Batterham AM: The development and evaluation of a novel computer program to assess previous-day dietary and physical activity behaviours in school children: the Synchronised Nutrition and Activity Program (SNAP), Brit J Nutr 99:1266–1274, 2008. Nebes RD, Buysse DJ, Halligan EM, Houck PR, Monk TH: Self-reported sleep quality predicts poor cognitive performance in healthy older adults, J Gerontol B 64:180–187, 2009. Ngandu T, Lehtisalo J, Solomon A, Levalahti E, Ahtiluoto S, Antikainen R, Backman L, Hanninen T, Jula A, Laatikainen T, Lindstrom J, Mangialasche F, Paajanen T, Pajala S, Peltonen M, Rauramaa R, Stigsdotter-Neely A, Strandberg T, Tuomilehto J, Soininen H, Kivipelto M: A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial, Lancet 385:2255–2263, 2015.



602

22.  Nonpharmacologic Activity Interventions to Prevent Alzheimer’s Disease

Norton S, Matthews FE, Barnes DE, Yaffe K, Brayne C: Potential for primary prevention of Alzheimer’s disease: an analysis of population-based data, Lancet Neurol 13:788–794, 2014. Ohayon MM: Epidemiology of insomnia: what we know and what we still need to learn, Sleep Med Rev 6:97–111, 2002. Palleschi L, Vetta F, De Gennaro E, Idone G, Sottosanti G, Gianni W, Marigliano V: Effect of aerobic training on the cognitive performance of elderly patients with senile dementia of Alzheimer type, Arch Gerontol Geriatr 22(Suppl 1):47–50, 1996. Parisi J, Stine-Marrow EAL, Noh SR, Morrow DG: Predispositional engagement, activity engagement, and cognition among older adults, Aging Neuropsychol Cogn 16:485–504, 2009. Park DC, Lodi-Smith J, Drew L, Haber S, Hebrank A, Bischof GN, Aamodt W: The impact of sustained engagement on cognitive function in older adults: the Synapse Project, Psychol Sci 25:103–112, 2013. Park DC, Lodi-Smith J, Drew L, Haber S, Hebrank A, Bischof GN, Aamodt W: The impact of sustained engagement on cognitive function in older adults: the Synapse Project, Psychol Sci 25:103–112, 2014. Pate RR, Pratt M, Blair SN, Haskell WL, Macera CA, Bouchard C, Buchner D, Ettinger W, Heath GW, King AC, et al: Physical activity and public health: a recommendation from the Centers for Disease Control and Prevention and the American College of Sports Medicine, J Am Med Assoc 273:402–407, 1995. Patel NK, Newstead AH, Ferrer RL: The effects of yoga on physical functioning and health related quality of life in older adults: a systematic review and meta-analysis, J Altern Complement Med 18:902–917, 2011. Pereira AC, Heddleston DE, Brickman AM, Sosunov AA, Hen R, McKhann GM, Sloan R, Gage FH, Brown TR, Small SA: An in vivo correlate of exercise-induced neurogenesis in the adult dentate gyrus, Proc Natl Acad Sci USA 104:5638–5643, 2007. Podewils LJ, Guallar E, Kuller LH, Fried LP, Lopez OL, Carlson M, Lyketsos CG: Physical activity, APOE genotype, and dementia risk: findings from the Cardiovascular Health Cognition Study, Am J Epidemiol 161:639–651, 2005. Pushkar D, Arbuckle T, Conway M, Chaikelson J, Maag U: Everyday activity parameters and competence in older adults, Psychol Aging 12:600–609, 1997. Pushkar D, Etezadi J, Andres D, Arbuckle T, Schwartzman AE, Chaikelson J: Models of intelligence in late life: comment on Hultsch et al. (1999), Psychol Aging 14:520–527, 1999. Randall T, Baetz B: Evaluating pedestrian connectivity for suburban sustainability, J Urban Plann Dev 127:1–15, 2001. Raz N: Aging of the brain and its impact on cogntive performance: integration of structural and functional findings. In Craik FIM, Salthouse TA, editors: The handbook of aging and cognition, ed 2, Mahwah, NJ, 2000, Erlbaum. Raz N, Rodrigue KM: Differential aging of the brain: patterns, cognitive correlates and modifiers, Neurosci Biobehav Rev 30:730–748, 2006. Raz N, Gunning-Dixon FM, Head D, Dupuis JH, Acker JD: Neuroanatomical correlates of cognitive aging: evidence from structural magnetic resonance imaging, Neuropsychology 12:95–114, 1998. Raz N, Rodrigue KM, Acker JD: Hypertension and the brain: vulnerability of the prefrontal regions and executive functions, Behav Neurosci 117:1169–1180, 2003. Raz N, Rodrigue KM, Head D, Kennedy KM, Acker JD: Differential aging of the medial temporal lobe: a study of a five-year change, Neurology 62:433–438, 2004. Rebok GW, Carlson MC, Barron JS, Frick KD, McGill S, Parisi JM, Seeman T, Tan EJ, Tanner EK, Willging PR, Fried LP: Experience Corps®: a civic engagement-based public health intervention in the public schools. Enhancing cognitive fitness in adults, New York, 2011, Springer, pp 469–487. Rebok GW, Ball K, Guey LT, Jones RN, Kim HY, King JW, Marsiske M, Morris JN, Tennstedt SL, Unverzagt FW: Ten-year effects of the advanced cognitive training for independent and vital elderly cognitive training trial on cognition and everyday functioning in older adults, J Am Geriatr Soc 62:16–24, 2014. Rogers RL, Meyer JS, Mortel KF: After reaching retirement age physical activity sustains cerebral perfusion and cognition, J Am Geriatr Soc 38:123–128, 1990. Ross A, Thomas S: The health benefits of yoga and exercise: a review of comparison studies, J Altern Complement Med 16:3–12, 2010. Saczynski JS, Pfeifer LA, Masaki K, Korf ES, Laurin D, White L, Launer LJ: The effect of social engagement on incident dementia: the Honolulu–Asia Aging Study, Am J Epidemiol 163:433–440, 2006. Saelens BE, Sallis JF, Frank LD: Environmental correlates of walking and cycling: findings from the transportation, urban design, and planning literatures, Ann Behav Med 25:80–91, 2003. Sale A, Berardi N, Maffei L: Enrich the environment to empower the brain, Trends Neurosci 32:233–239, 2009.



REFERENCES 603

Scarmeas N, Levy G, Tang MX, Manly J, Stern Y: Influence of leisure activity on the incidence of Alzheimer’s disease, Neurology 57:2236–2242, 2001. Scherder EJ, Van Paasschen J, Deijen JB, Van Der Knokke S, Orlebeke JF, Burgers I, Devriese PP, Swaab DF, Sergeant JA: Physical activity and executive functions in the elderly with mild cognitive impairment, Aging Ment Health 9:272–280, 2005. Schooler C, Mulatu MS, Oates G: The continuing effects of substantively complex work on the intellectual functioning of older workers, Psychol Aging 14:483–506, 1999. Seeman TE, Kaplan GA, Cohen R, Guralnik J: Social network ties and mortality among the elderly in the Alameda County Study, Am J Epidemiol 126:714–723, 1987. Seeman TE, Rodin J, Albert M: Self-efficacy and cognitive performance in high-functioning older individuals: MacArthur Studies of Successful Aging, J Aging Health 5:455–474, 1993. Seeman T, Berkman L, Charpentier P, Blazer D, Albert M, Tinetti M: Behavioral and psychosocial predictors or physical performance: MacArthur Studies of Successful Aging, J Gerontol 50A:M177–M183, 1995. Smith G, Housen P, Yaffe K, Ruff R, Kennison RF, Mahncke HW, Zelinski EM: A cognitive training program based on principles of brain plasticity: results from improvement in memory with plasticity-based adaptive cognitive training (IMPACT) study, J Am Geriatr Soc 57:594–603, 2009. Smith PJ, Blumenthal JA, Hoffman BM, Cooper H, Strauman TA, Welsh-Bohmer K, Browndyke JN, Sherwood A: Aerobic exercise and neurocognitive performance: a meta-analytic review of randomized controlled trials, Psychosom Med 72:239–252, 2010. Spira AP, Friedman L, Beaudreau SA, Ancoli-Israel S, Hernandez B, Sheikh J, Yesavage J: Sleep and physical functioning in family caregivers of older adults with memory impairment, Int Psychogeriatr 22:306–311, 2010. Spira AP, Covinsky K, Rebok GW, Punjabi NM, Stone KL, Hillier TA, Ensrud KE, Yaffe K: Poor sleep quality and functional decline in older women, J Am Geriatr Soc 60:1092–1098, 2012. Spira AP, Gamaldo AA, An Y, Wu MN, Simonsick EM, Bilgel M, Zhou Y, Wong DF, Ferrucci L, Resnick SM: Selfreported sleep and beta-amyloid deposition in community-dwelling older adults, JAMA Neurol 70:1537–1543, 2013. Stern Y, Albert S, Tang MX, Tsai WY: Rate of memory decline in AD is related to education and occupation: cognitive reserve? Neurology 53:1942–1947, 1999. Stewart AL, Mills KM, King AC, Haskell WL, Gillis D, Ritter PL: CHAMPS physical activity questionnaire for older adults: outcomes for interventions, Med Sci Sports Exerc 33:1126–1141, 2001. Stine-Morrow EA, Parisi JM, Morrow DG, Greene J, Park DC: An engagement model of cognitive optimization through adulthood, J Gerontol B 62(Spec No 1):62–69, 2007. Stine-Morrow EA, Parisi JM, Morrow DG, Park DC: The effects of an engaged lifestyle on cognitive vitality: a field experiment, Psychol Aging 23:778, 2008. Stine-Morrow EA, Payne BR, Roberts BW, Kramer AF, Morrow DG, Payne L, Hill PL, Jackson JJ, Gao X, Noh SR, Janke MC, Parisi JM: Training versus engagement as paths to cognitive enrichment with aging, Psychol Aging 29:891–906, 2014. Tan EJ, Xue QL, Li T, Carlson M, Fried LP: Volunteering: a physical activity intervention for older adults—the Experience Corps® program in Baltimore, J Urban Health 83:954–969, 2006. Tang YY, Ma Y, Wang J, Fan Y, Feng S, Lu Q, Yu Q, Sui D, Rothbart MK, Fan M, Posner MI: Short-term meditation training improves attention and self-regulation, Proc Natl Acad Sci USA 104:17152–17156, 2007. Taylor SE, Klein LC, Lewis BP, Gruenewald TL, Gurung RA, Updegraff JA: Biobehavioral responses to stress in females: tend-and-befriend, not fight-or-flight, Psychol Rev 107:411–429, 2000. Taylor-Piliae RE, Newell KA, Cherin R, Lee MJ, King AC, Haskell WL: Effects of tai chi and Western exercise on physical and cognitive functioning in healthy community-dwelling older adults, J Aging Phys Act 18:261–279, 2010. Tennstedt SL, Unverzagt FW: The ACTIVE Study: study overview and major findings, J Aging Health 25:3S–20S, 2013. Tworoger SS, Lee S, Schernhammer ES, Grodstein F: The association of self-reported sleep duration, difficulty sleeping, and snoring with cognitive function in older women, Alzheimer Dis Assoc Disord 20:41–48, 2006. Unger JB, Johnson CA, Marks G: Functional decline in the elderly: evidence for direct and stress-buffering protective effects of social interactions and physical activity, Ann Behav Med 19:152–160, 1997. U.S. Department of Health and Human Services: Physical Activity Guidelines Advisory Committee report, Washington, DC, 2008, Physical Activity Guidelines Advisory Committee. van der Bij AK, Laurant MG, Wensing M: Effectiveness of physical activity interventions for older adults: a review, Am J Prev Med 22:120–133, 2002.



604

22.  Nonpharmacologic Activity Interventions to Prevent Alzheimer’s Disease

van Praag H, Christie BR, Sejnowski TJ, Gage FH: Running enhances neurogenesis, learning, and long-term potentiation in mice, Proc Natl Acad Sci USA 96:13427–13431, 1999a. van Praag H, Kempermann G, Gage FH: Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus, Nat Neurosci 2:266–270, 1999b. Vaynman S, Ying Z, Gomez-Pinilla F: Hippocampal BDNF mediates the efficacy of exercise on synaptic plasticity and cognition, Eur J Neurosci 20:2580–2590, 2004. Verghese J, Lipton RB, Katz MJ, Hall CB, Derby CA, Kuslansky G, Ambrose AF, Sliwinski M, Buschke H: Leisure activities and the risk of dementia in the elderly, N Engl J Med 348:2508–2516, 2003. Varma V, Chuang Y, Harris G, Tan E, Carlson M: Low-intensity daily walking activity is associated with hippocampal volume in older adults, Hippocampus 25(5):605–615, 2014. Voss MW, Carr LJ, Clark R, Weng T: Revenge of the “sit” II: does lifestyle impact neuronal and cognitive health through distinct mechanisms associated with sedentary behavior and physical activity? Ment Health Phys Act 7:9–24, 2014. Wang HX, Karp A, Winblad B, Fratiglioni L: Late-life engagement in social and leisure activities is associated with a decreased risk of dementia: a longitudinal study from the Kungsholmen project, Am J Epidemiol 155:1081–1087, 2002. West RL: An application of prefrontal cortext function theory to cognitve aging, Psychol Bull 120:272–292, 1996. Wilson RS, Bennett DA, Beckett LA, Morris MC, Gilley DW, Bienias JL, Scherr PA, Evans DA: Cognitive activity in older persons from a geographically defined population, J Gerontol B 54:P155–P160, 1999. Wilson RS, Mendes De Leon CF, Barnes LL, Schneider JA, Bienias JL, Evans DA, Bennett DA: Participation in cognitively stimulating activities and risk of incident Alzheimer disease, J Am Med Assoc 287:742–748, 2002. World Health Organization: Dementia: a public health priority, World Health Organization, 2012. Yoshitake T, Kiyohara Y, Kato I, Ohmura T, Iwamoto H, Nakayama K, Ohmori S, Nomiyama K, Kawano H, Ueda K, et al: Incidence and risk factors of vascular dementia and Alzheimer’s disease in a defined elderly Japanese population: the Hisayama Study, Neurology 45:1161–1168, 1995. Zeidan F, Johnson SK, Diamond BJ, David Z, Goolkasian P: Mindfulness meditation improves cognition: evidence of brief mental training, Conscious Cogn 19:597–605, 2010. Zunzunegui MV, Alvarado BE, Del Ser T, Otero A: Social networks, social integration, and social engagement determine cognitive decline in community-dwelling Spanish older adults, J Gerontol B 58:S93–S100, 2003.