Measures of brain and hippocampal volume in 40 healthy young (aged 18–30 years) and 36 healthy elderly (aged 60–83 years) subjects were compared with composite cognitive function scores in three conceptual domains: memory ability, processing speed, and general fluid intelligence. Through a series of general linear models testing the relationship between these brain measures and cognitive performance scores, a significant positive relationship between hippocampal volume and fluid intelligence ability was found in elderly subjects but not in young. No relationship between the other cognitive domains and brain or hippocampal volume was found. The findings suggest a role of hippocampal atrophy in the decline in fluid intelligence in the elderly.
Aging; Hippocampus; Brain atrophy; Cognitive decline; Fluid intelligence; Memory
We propose a new Bayesian classifier, based on the recently introduced causal Markov random field (MRF) model, Quadrilateral MRF (QMRF). We use a second order inhomogeneous anisotropic QMRF to model the prior and likelihood probabilities in the maximum a posteriori (MAP) classifier, named here as MAP-QMRF. The joint distribution of QMRF is given in terms of the product of two dimensional clique distributions existing in its neighboring structure. 20 manually labeled human brain MR images are used to train and assess the MAP-QMRF classifier using the jackknife validation method. Comparing the results of the proposed classifier and FreeSurfer on the Dice overlap measure shows an average gain of 1.8%. We have performed a power analysis to demonstrate that this increase in segmentation accuracy substantially reduces the number of samples required to detect a 5% change in volume of a brain region.
MRF; Causal MRF; Quadrilateral MRF; MRI; brain image segmentation
In Alzheimer’s disease (AD), cognition and function are only moderately correlated in cross-sectional studies, and studies of their longitudinal association are less common. One potential non-cognitive contributor to function is depression, which has been associated with poorer clinical outcomes. The current study investigated longitudinal associations between functional abilities, cognitive status, and depressive symptoms in AD. 517 patients diagnosed with probable AD and enrolled in The Multicenter Study of Predictors of Disease Course in Alzheimer’s Disease were included. Patients were followed at 6-month intervals over 5.5 years. Longitudinal changes in the Blessed Dementia Rating Scale, modified Mini-Mental State Exam, and the depression subscale of the Columbia University Scale for Psychopathology in AD were examined in a multivariate latent growth curve model that controlled for gender, age, education, and recruitment site. Results showed that cognition and function worsened over the study period, whereas depressive symptoms were largely stable. Rates of change in cognition and function were correlated across participants and coupled within participants, indicating that they travel together over time. Worse initial cognitive status was associated with faster subsequent functional decline, and vice versa. Higher level of depressive symptoms was associated with worse initial functioning and faster subsequent cognitive and functional decline. These findings highlight the importance of both cognitive and psychiatric assessment for functional prognosis. Targeting both cognitive and depressive symptoms in the clinical treatment of AD may have incremental benefit on functional abilities.
Activities of daily living; Alzheimer’s disease; depression; statistical models
To investigate the temporal ordering of cognitive and functional declines separately in older adults with or without Alzheimer’s disease (AD).
Design and Setting
A community-based longitudinal study of aging and dementia in Northern Manhattan (Washington Heights/Hamilton Heights Inwood Columbia Aging Project) and a multicenter, clinic-based longitudinal study of prevalent AD at Columbia University Medical Center, Johns Hopkins School of Medicine, Massachusetts General Hospital, and the Hôpital de la Salpêtrière in Paris, France (the Predictors Study).
3,443 initially non-demented older adults (612 with eventual incident dementia) and 517 patients with AD.
Main Outcome Measures
Cognitive measures included the modified Mini-Mental State Exam and composite scores of memory and language derived from a standardized neuropsychological battery. Function was measured with the Blessed Dementia Rating Scale, completed by the participant (in the sample of non-demented older adults) or an informant (in the sample of prevalent AD patients). Data were analyzed with autoregressive cross-lagged panel analysis.
Cognitive scores more consistently predicted subsequent functional abilities than vice versa in non-demented older adults, participants with eventual incident dementia, and patients with prevalent AD.
Cognitive declines appear to precede and cause functional declines prior to and following dementia diagnosis. Standardized neuropsychological tests are valid predictors of later functional changes in both non-demented and demented older adults.
This study explored how the effectiveness of specific emotion regulation strategies might be influenced by aging and by time of day, given that in older age the circadian peak in cognitive performance is earlier in the day. We compared the benefit gained by 40 older (60–78 years; 20 women) and 40 younger (18–30 years; 20 women) adults during either on-peak or off-peak circadian times on 2 specific types of cognitive emotion regulation strategies: distraction and reappraisal. Participants rated their negative emotional responses to negative and neutral images under 3 conditions: a baseline nonregulation condition, a distraction condition involving a working memory task, and a reappraisal condition that involved reinterpreting the situation displayed using specific preselected strategies. First, as hypothesized, there was a crossover interaction such that participants in each age group reported more negative reactivity at their off-peak time of day. Second, a double dissociation was observed as circadian rhythms affected only negative reactivity—with reactivity highest at off-peak times—and aging diminished reappraisal but not distraction ability or reactivity. These findings add to growing evidence that understanding the effects of aging on emotion and emotion regulation depends on taking both time of day and type of regulatory strategy into account.
emotional reactivity; emotion regulation; cognitive reappraisal; aging; circadian rhythms
Cognitive reserve (CR) has been proposed as a latent variable that can account for the frequent discrepancy between an individual’s underlying level of brain pathology and their observed clinical outcome. A possible behavioral manifestation of CR is best strategy choice. Older adults have been shown to choose sub-optimal strategies for performing various tasks. The present study attempted to investigate whether greater levels of CR could predict greater strategy selection, particularly in older adults. A computational estimation task was administered to 20 healthy young adults (mean age = 24.7 ± 3.6; 20–31 years) and 18 healthy older adults (68.2 ± 4.5; 62–77 years) wherein participants needed to estimate the product of two two-digit numbers by using one of two strategies. The results revealed an effect of age group on strategy choice and supported the hypothesis that CR is associated with increased strategy selection abilities.
Aging; Cognitive reserve; Compensation; Strategy selection; Strategy adaptivity; Computational estimation
The default-mode network (DMN) has become a well accepted concept in cognitive and clinical neuroscience over the last decade, and perusal of the recent literature attests to a stimulating research field of cognitive and diagnostic applications (for example, (Andrews-Hanna, Reidler, Huang, & Buckner, 2010; Koch et al., 2010; Sheline, Barch et al., 2009; Sheline, Raichle et al., 2009; Uddin et al., 2008; Uddin, Kelly, Biswal, Castellanos, & Milham, 2009; Weng et al., 2009; Yan et al., 2009)). However, a formal definition of what exactly constitutes a functional brain network is difficult to come by. In recent contributions, some researchers argue that the DMN is best understood as multiple interacting subsystems (Buckner, Andrews-Hanna, & Schacter, 2008) and have explored modular components of the DMN that have different functional specialization and could to some extent be identified separately (Fox et al., 2005; Harrison et al., 2008; Uddin et al., 2009). Such conception of modularity seems to imply an opposite construct of a ‘unified whole’, but it is difficult to locate proponents of the idea of a DMN who are supplying constraints that can be brought to bear on data in rigorous tests. Our aim in this paper is to present a principled way of deriving a single covariance pattern as the neural substrate of the DMN, test to what extent its behavior tracks the coupling strength between critical seed regions, and investigate to what extent our stricter concept of a network is consistent with the already established findings about the DMN in the literature. We show that our approach leads to a functional covariance pattern whose pattern scores are a good proxy for the integrity of the connections between a medioprefrontal, posterior cingulate and parietal seed regions. Our derived DMN network thus has potential for diagnostic applications that are simpler to perform than computation of pairwise correlational strengths or seed maps.
Default-mode network; resting fMRI; spatial covariance analysis; Principal Components Analysis
We performed a delayed-item-recognition task to investigate the neural substrates of non-verbal visual working memory with event-related fMRI (‘Shape task’). 25 young subjects (mean age: 24.0 years; STD=3.8 years) were instructed to study a list of either 1,2 or 3 unnamable nonsense line drawings for 3 seconds (‘stimulus phase’ or STIM). Subsequently, the screen went blank for 7 seconds (‘retention phase’ or RET), and then displayed a probe stimulus for 3 seconds in which subject indicated with a differential button press whether the probe was contained in the studied shape-array or not (‘probe phase’ or PROBE). Ordinal Trend Canonical Variates Analysis (Habeck et al., 2005a) was performed to identify spatial covariance patterns that showed a monotonic increase in expression with memory load during all task phases. Reliable load-related patterns were identified in the stimulus and retention phase (p<0.01), while no significant pattern could be discerned during the probe phase. Spatial covariance patterns that were obtained from an earlier version of this task (Habeck et al., 2005b) using 1, 3, or 6 letters (‘Letter task’) were also prospectively applied to their corresponding task phases in the current non-verbal task version. Interestingly, subject expression of covariance patterns from both verbal and non-verbal retention phases correlated positively in the non-verbal task for all memory loads (p<0.0001). Both patterns also involved similar frontoparietal brain regions that were increasing in activity with memory load, and mediofrontal and temporal regions that were decreasing. Mean subject expression of both patterns across memory load during retention also correlated positively with recognition accuracy (dL) in the Shape task (p<0.005). These findings point to similarities in the neural substrates of verbal and non-verbal rehearsal processes. Encoding processes, on the other hand, are critically dependent on the to-be-remembered material, and seem to necessitate material-specific neural substrates.
multivariate analysis; visual working memory; encoding; maintenance
Effects of dual-responding on tracking performance after 49-hr of sleep deprivation (SD) were evaluated behaviorally and with functional magnetic resonance imaging (fMRI). Continuous visuomotor tracking was performed simultaneously with an intermittent color-matching visual detection task in which a pair of color-matched stimuli constituted a target and non-matches were non-targets. Tracking error means were binned time-locked to stimulus onset of the detection task in order to observe changes associated with dual-responding by comparing the error during targets and non-targets. Similar comparison was made with fMRI data. Our result showed that despite a significant increase in the overall tracking error post SD, from 20 pixels pre SD to 45 pixels post SD, error decreased to a minimum of about 25 pixels 0 to 6 s after dual-response. Despite an overall reduced activation post SD, greater activation difference between targets and non-targets was found post SD in task-related regions, such as the left cerebellum, the left somatosensory cortex, the left extrastriate cortex, bilateral precuneus, the left middle frontal gyrus, and the left motor cortex. Our results suggest that dual-response helps to alleviate performance impairment usually associated with SD. The duration of the alleviation effect was on the order of seconds after dual-responding.
Visuomotor tracking; Visual detection; Continuous wakefulness; Dual responses; Dual tasks; Prefrontal cortex
We investigated the feasibility of using the Space Fortress (SF) game, a complex video game originally developed to study complex skill acquisition in young adults, to improve executive control processes in cognitively healthy older adults. The study protocol consisted of 36 one-hour game play sessions over 3 months with cognitive evaluations before and after, and a follow-up evaluation at 6 months. Sixty participants were randomized to one of three conditions: Emphasis Change (EC) – elders were instructed to concentrate on playing the entire game but place particular emphasis on a specific aspect of game play in each particular game; Active Control (AC) – game play with standard instructions; Passive Control (PC) – evaluation sessions without game play. Primary outcome measures were obtained from five tasks, presumably tapping executive control processes. A total of 54 older adults completed the study protocol. One measure of executive control, WAIS-III letter–number sequencing, showed improvement in performance from pre- to post-evaluations in the EC condition, but not in the other two conditions. These initial findings are modest but encouraging. Future SF interventions need to carefully consider increasing the duration and or the intensity of the intervention by providing at-home game training, reducing the motor demands of the game, and selecting appropriate outcome measures.
Aging; Cognition; Intervention; Executive control; Video games
The concept of reserve arose from the mismatch between the extent of brain changes or pathology and the clinical manifestations of these brain changes. The cognitive reserve hypothesis posits that individual differences in the flexibility and adaptability of brain networks underlying cognitive function may allow some people to cope better with brain changes than others. Although there is ample epidemiologic evidence for cognitive reserve, the neural substrate of reserve is still a topic of ongoing research. Here we review some representative studies from our group that exemplify possibilities for the neural substrate of reserve including neural reserve, neural compensation, and generalized cognitive reserve networks. We also present a schematic overview of our ongoing research in this area.
The meanings of several target neuropsychological variables, including measures of executive functioning, were examined using contextual analysis across a sample of English-speakers and a sample of Spanish-speakers. Results of the contextual analysis, which examined the contributions of the latent constructs of memory, psychomotor speed, visual spatial ability, and knowledge and comprehension, to the target neuropsychological variables indicate that each of the target variables likely reflects the unique contribution of several reference abilities. These findings provide evidence that the neuropsychological variables are multi-dimensional. The patterns of relations were similar across the samples of English and Spanish speakers.
contextual analysis; executive functioning; memory; psychomotor speed; structural equation modeling; race; ethnicity; vascular cognitive impairment
The extent of task-related fMRI activation can vary as a function of task difficulty. Also the efficiency or capacity of the brain networks underlying task performance can change with aging. We asked whether the expression of a network underlying task performance would differ as a function of task demand in old and young individuals. 26 younger and 23 older healthy adults performed a delayed item recognition task that used the response signal method to parametrically manipulate the extrinsic difficulty of the task by imposing five different deadlines for recognition response. Both age groups showed a speed accuracy trade-off, but the younger group achieved greater discriminability at the longer deadlines. We identified a spatial pattern of fMRI activation during the probe phase whose expression increased as the response deadline shortened and the task became more difficult. This pattern was expressed to a greater degree by the old group at the long deadlines, when the task was easiest. By contrast, this pattern was expressed to greater degree by the younger group at the short deadlines, when the task was hardest. This suggests reduced efficiency and capacity of this network in older subjects. These findings suggest that neuroimaging studies comparing task-related activation across groups with different cognitive abilities must be interpreted in light of the relative difficulty of the task for each group.
fMRI; aging; working memory; speed-accuracy tradeoff
Subjects performed a continuous tracking concurrently with an intermittent visual detection task to investigate the existence of competition for a capacity-limited stage (a bottleneck stage). Both perceptual and response-related processes between the two tasks were examined behaviorally and the changes in brain activity during dual-tasking relative to single-task were also assessed. Tracking error and joystick speed were analyzed for changes that were time-locked to visual detection stimuli. The associated brain activations were examined with functional magnetic resonance imaging (fMRI). These were analyzed using mixed block and event-related models to tease apart sustained neural activity and activations associated with individual events. Increased tracking error and decreased joystick speed were observed relative to the target stimuli in the dual-task condition only, which supports the existence of a bottleneck stage in response-related processes. Neuroimaging data show decreased activation to target relative to non-target stimuli in the dual-task condition in the left primary motor and somatosensory cortices controlling right-hand tracking, consistent with the tracking interference observed in behavioral data. Furthermore, the ventral attention system, rather than the dorsal attention system, was found to mediate task coordination between tracking and visual detection.
fMRI; Compensatory tracking; Visual detection; Bottom-up attention system; Psychological refractory period; Dual-task interference
This functional neuroimaging (fMRI) study examined the neural networks (spatial patterns of covarying neural activity) associated with the speed-accuracy tradeoff (SAT) in younger adults. The response signal method was used to systematically increase probe duration (125, 250, 500, 1,000 2,000 ms) in a nonverbal delayed-item recognition task. A covariance-based multivariate approach identified three networks that varied with probe duration – indicating that the SAT is driven by three distributed neural networks.
Aging has a multi-faceted impact on brain structure, brain function and cognitive task performance, but the interaction of these different age-related changes is largely unexplored. We hypothesize that age-related structural changes alter the functional connectivity within the brain, resulting in altered task performance during cognitive challenges. In this neuroimaging study, we used independent components analysis to identify spatial patterns of coordinated functional activity involved in the performance of a verbal delayed item recognition task from 75 healthy young and 37 healthy old adults. Strength of functional connectivity between spatial components was assessed for age group differences and related to speeded task performance. We then assessed whether age-related differences in global brain volume were associated with age-related differences in functional network connectivity. Both age groups used a series of spatial components during the verbal working memory task and the strength and distribution of functional network connectivity between these components differed across the age groups. Poorer task performance, i.e. slower speed with increasing memory load, in the old adults was associated with decreases in functional network connectivity between components comprised of the supplementary motor area and the middle cingulate and between the precuneus and the middle/superior frontal cortex. Advancing age also led to decreased brain volume; however, there was no evidence to support the hypothesis that age-related alterations in functional network connectivity were the result of global brain volume changes. These results suggest that age-related differences in the coordination of neural activity between brain regions partially underlie differences in cognitive performance.
Cognitive reserve, broadly conceived, encompasses aspects of brain structure and function that optimize individual performance in the presence of injury or pathology. Reserve is defined as a feature of brain structure and/or function that modifies the relationship between injury or pathology and performance on neuropsychological tasks or clinical outcomes. Reserve is challenging to study for two reasons. The first is: reserve is a hypothetical construct, and direct measures of reserve are not available. Proxy variables and latent variable models are used to attempt to operationalize reserve. The second is: in vivo measures of neuronal pathology are not widely available. It is challenging to develop and test models involving a risk factor (injury or pathology), a moderator (reserve) and an outcome (performance or clinical status) when neither the risk factor nor the moderator are measured directly. We discuss approaches for quantifying reserve with latent variable models, with emphasis on their application in the analysis of data from observational studies. Increasingly latent variable models are used to generate composites of cognitive reserve based on multiple proxies. We review the theoretical and ontological status of latent variable modeling approaches to cognitive reserve, and suggest research strategies for advancing the field.
Cognitive reserve; Brain reserve; Latent variable; Aging; Cognition; Neuronal plasticity; Multivariate Analysis; Environment; Social Environment; Education; Social Class; Intelligence
White matter hyperintensities (WMH), visualized on T2-weighted MRI, are thought to reflect small-vessel vascular disease. Much like other markers of brain disease, the association between WMH and cognition is imperfect. The concept of reserve may account for this imperfect relationship. The purpose of this study was to test the reserve hypothesis in the association between WMH severity and cognition. We hypothesized that individuals with higher amounts of reserve would be able to tolerate greater amounts of pathology than those with lower reserve.
Neurologically healthy older adults (n=717) from a community-based study received structural MRI, neuropsychological assessment, and evaluation of reserve. WMH volume was quantified algorithmically. We derived latent constructs representing four neuropsychological domains, a measure of cognitive reserve, and a measure of brain reserve. Measures of cognitive and brain reserve consisted of psychosocial (e.g., education) and anthropometric (e.g., craniometry) variables, respectively.
Increased WMH volume was associated with poorer cognition and higher cognitive and brain reserve were associated with better cognition. Controlling for speed/executive function or for language function, those with higher estimates of cognitive reserve had significantly greater degrees of WMH volume, particularly among women. Controlling for cognitive functioning across all domains, individuals with higher estimates of brain reserve had significantly greater WMH volume.
For any given level of cognitive function, those with higher reserve had more pathology in the form of WMH, suggesting that they are better able to cope with pathology than those with lower reserve. Both brain reserve and cognitive reserve appear to mitigate the impact of pathology on cognition.
White matter hyperintensities; cognitive reserve; MRI; cognition
Recent studies suggest that individual hippocampal subregions perform distinct cognitive operations and are differentially targeted by aging and disease. Although originally developed to assess global hippocampal function, whether performance on standard memory tests used in neuropsychological batteries is associated with individual hippocampal subregions remains unknown. Here we addressed this issue by imaging 210 neuropsychologically-characterized subjects using a high-resolution variant of functional magnetic resonance imaging (fMRI) that generates maps reflective of basal hippocampal metabolism. Regression analysis revealed memory tests that differentially associate with 2 hippocampal subregions, the entorhinal cortex (EC) and the dentate gyrus (DG). Whereas performance on the delayed retention component of the Selective Reminding Test was associated with the EC, performance on the recognition component of the Benton Visual Retention Test was associated with the DG. Furthermore, elevation in blood glucose, previously shown to target the DG, was found to correlate selectively with the recognition component of the Benton Visual Retention Test. These findings provide further evidence that the hippocampal subregions perform distinct roles, and, interpreted in the context of previous neuropsychological and imaging studies, confirm that aging and Alzheimer’s disease target different hippocampal subregions.
Metacognitive methodologies are used to examine the integrity of self-referential processing in healthy adults, and have been implemented to study disorders of the self-concept in neurologic and psychiatric populations. However, the extent to which metacognitive evaluations assess a uniquely self-evaluative capacity that cannot be explained fully by primary cognitive functions, demographics, or mood is not clear. The objective of the current study was to examine whether metamemory and a metacognitive test of agency shared a self-referential association that would not be explained by cognition, demographics, or mood.
38 non-demented older adults (MMSE >=24 and mean age = 68.13) participated in metacognitive testing and completed cognitive testing and mood questionnaires. Bivariate correlations were used to evaluate the association between metamemory and agency, and to determine the cognitive (memory, attention, and executive functioning), demographic (age and education), and mood (anxiety and depression) correlates of each. Correlates of metamemory and agency were then entered into linear regression models to determine whether any association between metacognitive measures remained.
Metamemory was associated with agency judgments (n = 27), specifically those on self-controlled rather than computer-controlled trials (r = .41, p = .03). Regression results supported a role for agency in predicting metamemory, above and beyond memory and education (β = .39, p = .034). Metamemory was also an independent predictor of agency judgments (β = .36, p = .049).
The interrelation between metamemory and agency judgments suggests that metacognitive testing captures an important aspect of self-referential processing not otherwise assessed in a standard cognitive evaluation, and may provide unique information about self-evaluative capacities in clinical populations.
Metacognition; Metamemory; Agency; Self; Awareness
Age has a multifaceted impact on neural measures which are not always directly related to alterations in clinical and cognitive measures. This partial protection from the deleterious effects of age in some individuals is referred to as cognitive reserve (CR) and although linked to variations in intelligence and life experiences, its mechanism is still unclear. Within the framework of a theoretical model we tested two potential mechanistic roles of CR to maintain task performance, neural reserve and neural compensation, in young and older adults using functional and structural MRI. Neural reserve refers to increased efficiency and/or capacity of existing functional neural resources. Neural compensation refers to the increased ability to recruit new, additional functional resources. Using structural and functional measures and task performance, the roles of CR were tested using path analysis. Results supported both mechanistic theories of CR and the use of our general theoretical model.
Aging; cognitive reserve; multi-modal neuroimaging; path analysis; function; structure
Spatiotemporal and recognition memory are affected by aging in humans and macaque monkeys. To investigate whether these deficits are coupled with atrophy of memory-related brain regions, T1-weighted magnetic resonance images were acquired and volumes of the cerebrum, ventricles, prefrontal cortex (PFC), calcarine cortex, hippocampus, and striatum were quantified in young and aged rhesus monkeys. Subjects were tested on a spatiotemporal memory procedure (delayed response [DR]) that requires the integrity of the PFC and a medial temporal lobe-dependent recognition memory task (delayed nonmatching to sample [DNMS]). Region of interest analyses revealed that age inversely correlated with striatal, dorsolateral prefrontal cortex (dlPFC), and anterior cingulate cortex volumes. Hippocampal volume predicted acquisition of the DR task. Striatal volume correlated with DNMS acquisition, whereas total prefrontal gray matter, prefrontal white matter, and dlPFC volumes each predicted DNMS accuracy. A regional covariance analysis revealed that age-related volumetric changes could be captured in a distributed network that was coupled with declining performance across delays on the DNMS task. This volumetric analysis adds to growing evidence that cognitive aging in primates arises from region-specific morphometric alterations distributed across multiple memory-related brain systems, including subdivisions of the PFC.
age-related memory impairment; medial temporal lobe; MRI; prefrontal cortex; rhesus monkey
Cognitive reserve explains why those with higher IQ, education, occupational attainment, or participation in leisure activities evidence less severe clinical or cognitive changes in the presence of age-related or Alzheimer’s disease pathology. Specifically, the cognitive reserve hypothesis is that individual differences in how tasks are processed provide reserve against brain pathology. Cognitive reserve may allow for more flexible strategy usage, an ability thought to be captured by executive functions tasks. Additionally, cognitive reserve allows individuals greater neural efficiency, greater neural capacity, and the ability for compensation via the recruitment of additional brain regions. Taking cognitive reserve into account may allow for earlier detection and better characterization of age-related cognitive changes and Alzheimer’s disease. Importantly, cognitive reserve is not fixed but continues to evolve across the lifespan. Thus, even late-stage interventions hold promise to boost cognitive reserve and thus reduce the prevalence of Alzheimer’s disease and other age-related problems.
aging; Alzheimer’s disease; brain reserve; cognitive reserve; neural reserve; neural compensation
To examine the association between physical activity (PA) and Alzheimer's disease (AD) course.
PA has been related to lower risk for AD. Whether PA is associated with subsequent AD course has not been investigated.
In a population-based study of individuals ≥65 in New York who were prospectively followed with standard neurological and neuropsychological evaluations (every ~1.5 years), 357 participants (i) were non-demented at baseline and (ii) were diagnosed with AD during follow-up (incident AD). PA (sum of participation in a variety of physical activities, weighted by the type of activity [light, moderate, severe]) obtained 2.4 (sd. 1.9) years before incidence was the main predictor of mortality in Cox models and of cognitive decline in GEE models that were adjusted for age, gender, ethnicity, education, comorbidities and duration between PA evaluation and dementia onset.
150 incident AD cases (54%) died during the course of 5.2 (sd 4.4) years of follow-up. As compared to incident AD cases who were physically inactive, those with some PA had lower mortality risk, while incident AD participants with much PA had an even lower risk. Additional adjustments for APOE genotype, smoking, comorbidity index and cognitive performance did not change the associations. PA did not affect rates of cognitive or functional decline.
Exercise may affect not only risk for AD but also subsequent disease duration: more PA is associated with prolonged survival in AD.
Alzheimer's disease; Epidemiology