Group Of Healthy Older Adults Research Articles

The mark of adaptive memory in healthy and cognitively impaired older adults and elderly

AbstractThe survival processing paradigm has recently drawn attention to the functional aspects of memory functioning. The survival effect, characterized by better memory performance when information is processed in a survival context, as compared with a variety of controls, is now well established in healthy populations. The main goal of this study was to test this paradigm in a group of cognitively impaired older adults and elderly; their data were compared to the data obtained in a group of healthy older adults and elderly. Seventeen cognitively impaired and 17 healthy participants performed a typical survival task using a blocked within‐subject design procedure and free recall as the memory test. The healthy older adults and elderly performed better on this memory task as well as on other tests included in a neuropsychological evaluation protocol. Importantly, both groups benefited from survival processing. These results provide further support for the power of survival processing, extending this phenomenon to cognitively impaired aging participants. The data also suggest that the survival effect is not simply a form of deep processing. Potential applied considerations are presented.

Neuromagnetic beta and gamma oscillations in the somatosensory cortex after music training in healthy older adults and a chronic stroke patient

ObjectiveExtensive rehabilitation training can lead to functional improvement even years after a stroke. Although neuronal plasticity is considered as a main origin of such ameliorations, specific subtending mechanisms need further investigation. Our aim was to obtain objective neuromagnetic measures sensitive to brain reorganizations induced by a music-supported training. MethodsWe applied 20-Hz vibrotactile stimuli to the index finger and the ring finger, recorded somatosensory steady-state responses with magnetoencephalography, and analyzed the cortical sources displaying oscillations synchronized with the external stimuli in two groups of healthy older adults before and after musical training or without training. In addition, we applied the same analysis for an anecdotic report of a single chronic stroke patient with hemiparetic arm and hand problems, who received music-supported therapy (MST). ResultsHealthy older adults showed significant finger separation within the primary somatotopic map. Beta dipole sources were more anterior located compared to gamma sources. An anterior shift of sources and increases in synchrony between the stimuli and beta and gamma oscillations were observed selectively after music training. In the stroke patient a normalization of somatotopic organization was observed after MST, with digit separation recovered after training and stimulus induced gamma synchrony increased. ConclusionsThe proposed stimulation paradigm captures the integrity of primary somatosensory hand representation. Source position and synchronization between the stimuli and gamma activity are indices, sensitive to music-supported training. Responsiveness was also observed in a chronic stroke patient, encouraging for the music-supported therapy. Notably, changes in somatosensory responses were observed, even though the therapy did not involve specific sensory discrimination training. SignificanceThe proposed protocol can be used for monitoring changes in neuronal organization during training and will improve the understanding of the brain mechanisms underlying rehabilitation.

P 171. Bihemispheric motor cortex stimulation in older adults induces modulations of resting state and task-related activity

Bihemispheric transcranial direct current stimulation (“dual” tDCS) of primary motor cortices has been described to enhance motor learning in healthy subjects and to facilitate motor recovery after stroke. In order to investigate the neural correlates of its mode of action, we compared different tDCS montages in a group of healthy older adults in a cross-over design (‘dual’ vs. ‘anodal’ vs. ‘sham’). 20 subjects (mean age 68.7 ± 4.7 years, all right-handed) underwent tDCS and simultaneous MRI at 3T, including resting state fMRI and a choice reaction time task. In the task, subjects were presented with different symbols in a randomized order and required to respond with button presses using either left or right index fingers. In both active stimulation conditions, the anode was placed over left primary motor cortex (M1). The cathode was positioned over right M1 (dual) or the contralateral supraorbital region (anodal). The current was constantly delivered during resting state and task-related fMRI. Task-related fMRI analysis was carried out with SPM8; resting state data were analyzed with Lipsia using low-frequency spectral Eigenvector Centrality Mapping (ECM). Task-specific analyses revealed differential effects of the two active tDCS conditions. Compared with anodal tDCS, dual tDCS yielded stronger activations in bilateral primary motor cortices when either the left or right index fingers were used. In the resting state analysis, ECM values in left prefrontal and cingulate cortices were higher in the dual condition as compared to sham. Anodal yielded higher ECM values in the left prefrontal as well as left ventral premotor cortex when compared with sham; lower values were found in right M1 and the left precuneus. Comparing the two active tDCS conditions, increased connectivity of the cingulate cortex and decreased connectivity in the right cerebellum was found under dual compared to anodal tDCS (all p < .001, Monte Carlo-corrected). In conclusion, tDCS induced specific changes of M1 activation in task-specific activations, dependent on the electrode set-up. As a complement, the resting state analysis demonstrated altered connectivity within a multimodal network including motor cortices as well as prefrontal regions, indicating that the previously documented stronger behavioral effects of dual as compared to anodal tDCS may not be merely mediated by a “simple” add-on effect of cathodal stimulation, but rather due to complex bihemispheric network modulations.

Disrupted cortico-cerebellar connectivity in older adults

Healthy aging is marked by declines in a variety of cognitive and motor abilities. A better understanding of the aging brain may aid in elucidating the neural substrates of these behavioral effects. Investigations of resting state functional brain connectivity have provided insights into pathology, and to some degree, healthy aging. Given the role of the cerebellum in both motor and cognitive behaviors, as well as its known volumetric declines with age, investigating cerebellar networks may shed light on the neural bases of age-related functional declines. We mapped the resting state networks of the lobules of the right hemisphere and the vermis of the cerebellum in a group of healthy older adults and compared them to those of young adults. We report disrupted cortico-cerebellar resting state network connectivity in older adults. These results remain even when controlling for cerebellar volume, signal-to-noise ratio, and signal-to-fluctuation noise ratio. Specifically, there was consistent disruption of cerebellar connectivity with both the striatum and the medial temporal lobe. Associations between connectivity strength and both sensorimotor and cognitive task performances indicate that cerebellar engagement with the default mode network and striatal pathways is associated with better performance for older adults. These results extend our understanding of the resting state networks of the aging brain to include cortico-cerebellar networks, and indicate that age differences in network connectivity strength are important for behavior.

Three-Month Stability of the CogState Brief Battery in Healthy Older Adults, Mild Cognitive Impairment, and Alzheimer's Disease: Results from the Australian Imaging, Biomarkers, and Lifestyle-Rate of Change Substudy (AIBL-ROCS)

Large prospective studies of Alzheimer's disease (AD) have sought to understand the pathological evolution of AD and factors that may influence the rate of disease progression. Estimates of rates of cognitive change are available for 12 or 24 months, but not for shorter time frames (e.g., 3 or 6 months). Most clinical drug trials seeking to reduce or modify AD symptoms have been conducted over 12- or 24-week periods. As such, we aimed to characterize the performance of a group of healthy older adults, adults with amnestic mild cognitive impairment (aMCI), and adults with AD on the CogState battery of tests over short test-retest intervals. This study recruited 105 healthy older adults, 48 adults with aMCI, and 42 adults with AD from the Australian Imaging, Biomarkers, and Lifestyle study and administered the CogState battery monthly over 3 months. The CogState battery of tests showed high test-retest reliability and stability in all clinical groups when participants were assessed over 3 months. When considered at baseline, the CogState battery of tests was able to detect AD-related cognitive impairment. The data provide important estimates of the reliability, stability, and variability of each cognitive test in healthy older adults, adults with aMCI, and adults with AD. This may potentially be used to inform future estimates of cognitive change in clinical trials.

Decline in Cognitive Function over 18 Months in Healthy Older Adults with High Amyloid-β

We aimed to characterize the nature and magnitude of cognitive decline in a group of healthy older adults with high and low levels of amyloid-β (Aβ) and who were APOE ε4 carriers and non-carriers. Healthy older adults underwent positron emission tomography neuroimaging for Aβ, APOE genotyping, and cognitive and clinical assessment as part of their baseline assessment in the Australian Imaging, Biomarker, and Lifestyle study. Cognitive function and clinical ratings were reassessed 18 months later. Linear mixed model analyses adjusted for baseline cognitive function indicated that relative to healthy older adults with low Aβ, healthy older adults with high Aβ showed greater decline in episodic memory and language at 18 months. No decline on any measure of executive function, attention, or clinical rating was observed for healthy older adults with high Aβ levels. Compared to non-carriers, APOE ε4 carriers showed a greater decline only on the task of visual memory at the 18 month assessment. Importantly though, no interaction between APOE ε4 and Aβ was observed on any measure of cognitive function. The results of this study suggest that high Aβ load was associated with greater decline in episodic memory and language, that the magnitude of this decline was moderate and equivalent across both domains, and that APOE ε4 carriage did not moderate the relationship between Aβ and decline in memory and language functions.

Does combined cognitive training and physical activity training enhance cognitive abilities more than either alone? A four-condition randomized controlled trial among healthy older adults

Cognitive training and aerobic training are known to improve cognitive functions. To examine the separate and combined effects of such training on cognitive performance, four groups of healthy older adults embarked on a 4 months cognitive and/or mild aerobic training. A first group [n = 33, mean age = 80 (66–90)] engaged in cognitive training, a second [n = 29, mean age = 81 (65–89)] in mild aerobic training, a third [n = 29, mean age = 79 (70–93)] in the combination of both, and a fourth [n = 31, mean age = 79 (71–92)] control group engaged in book-reading activity. The outcome was a well-validated multi-domain computerized cognitive evaluation for older adults. The results indicate that, when compared to older adults who did not engage in cognitive training (the mild aerobic and control groups) older adults who engaged in cognitive training (separate or combined training groups) showed significant improvement in cognitive performance on Hand-Eye Coordination, Global Visual Memory (GVM; working memory and long-term memory), Speed of Information Processing, Visual Scanning, and Naming. Indeed, individuals who did not engage in cognitive training showed no such improvements. Those results suggest that cognitive training is effective in improving cognitive performance and that it (and not mild aerobic training) is driving the improvement in the combined condition. Results are discussed in terms of the special circumstances of aerobic and cognitive training for older adults who are above 80 years of age.

Activity Levels in Healthy Older Adults: Implications for Joint Arthroplasty

This work evaluated activity levels in a group of healthy older adults to establish a target activity level for adults of similar age after total joint arthroplasty (TJA). With the decreasing age of TJA patients, it is essential to have a reference for activity level in younger patients as activity level affects quality of life and implant design. 54 asymptomatic, healthy older adults with no clinical evidence of lower extremity OA participated. The main outcome measure, average daily step count, was measured using an accelerometer-based activity monitor. On average the group took 8813 ± 3611 steps per day, approximately 4000 more steps per day than has been previously reported in patients following total joint arthroplasty. The present work provides a reference for activity after joint arthroplasty which is relevant given the projected number of people under the age of 65 who will undergo joint arthroplasty in the coming years.

Semantic verbal fluency strategies in amnestic mild cognitive impairment.

The primary aim of this study was to investigate the cognitive strategies used in semantic fluency (clustering, switching, and access to subcategories) in amnestic mild cognitive impairment (aMCI). In addition, we evaluated the impact of slowing in speed of information processing on semantic fluency performance. Tests of semantic verbal fluency (animals, supermarket items) were administered to 33 participants with aMCI and 33 healthy older adults (HOA). A selected measure of speed of information processing was also administered. Analyses revealed significant impairment in word generation (animals, supermarket items) in the aMCI group relative to the HOA group (η² = .41). Furthermore, the aMCI group produced significantly smaller cluster sizes (η² = .12) and accessed fewer subcategories than the HOA group (η² = .11), whereas a difference in switching frequency between groups produced a small but nonsignificant effect. Although the aMCI group, as compared with the HOA group, demonstrated reductions in processing speed (η² = .17), covariance analyses adjusting for speed did not substantively alter the significant difference between groups in clustering and access to subcategories. When attempting semantic fluency, and as compared with healthy older adults, people with aMCI demonstrated difficulties in isolating semantic categories and loss of associative links within semantic categories. These findings are discussed in relation to an early degradation of semantic memory in aMCI.

Age-Related Influences of Prior Sleep on Brain Activation during Verbal Encoding

Disrupted sleep is more common in older adults (OLD) than younger adults (YOUNG), often co-morbid with other conditions. How these sleep disturbances affect cognitive performance is an area of active study. We examined whether brain activation during verbal encoding correlates with sleep quantity and quality the night before testing in a group of healthy OLD and YOUNG. Twenty-seven OLD (ages 59–82) and 27 YOUNG (ages 19–36) underwent one night of standard polysomnography. Twelve hours post-awakening, subjects performed a verbal encoding task while undergoing functional magnetic resonance imaging. Analyses examined the group (OLD vs. YOUNG) by prior sleep quantity (total sleep time, TST) or quality (sleep efficiency, SE) interaction on cerebral activation, controlling for performance. Longer TST promoted higher levels of activation in the bilateral anterior parahippocampal in OLD and lower activation levels in the left anterior parahippocampus in YOUNG. Greater SE promoted higher activation levels in the left posterior parahippocampus and right inferior frontal gyrus in YOUNG, but not in OLD. The roles of these brain regions in verbal encoding suggest, in OLD, longer sleep duration may be linked to the ability to engage in functional compensation during cognitive challenges. By contrast, in YOUNG, shorter sleep duration may necessitate functional compensation to maintain cognitive performance, similar to what is seen following acute sleep deprivation. Additionally, in YOUNG, better sleep quality may improve semantic retrieval processes, thereby aiding encoding.

Functional phenotyping of successful aging in long‐term memory: Preserved performance in the absence of neural compensation

We investigated whether preservation of encoding-related brain activity patterns in older age reflects successful aging in long-term memory. Using a statistical matching technique, we identified groups of healthy older adults with different degrees of Functional Activity Deviation during Encoding (FADE) from young adults in a memory network comprising hippocampal, temporal, occipital, and retrosplenial regions. High FADE scores were associated with impairment in recollection, abnormal activity in the default mode network, and lower gray matter density in bilateral ventral prefrontal cortex and left rhinal cortex; a constellation previously associated with increased risk for dementia. Low FADE scores functionally phenotyped successful aging because recollection was well preserved and there was no evidence for compensatory prefrontal activation. Thus, for some individuals successful aging in long-term memory reflects the preservation of a functionally specific memory network, and can occur in the absence of compensatory brain activity.

Nutritional predictors of muscle protein metabolism and function in older adults

Sarcopenia contributes to frailty in older adults and is associated with alterations in muscle protein metabolism. The purpose of this research was to examine the potential predictors of muscle protein synthesis and function in elders.MethodsWe report preliminary data from a subset of 8 healthy, sedentary subjects (69.5±3.4 yrs, BMI ≤30kg·m−2) enrolled in a larger study who met their dietary requirements. Linear regressions were carried out on the following variables: muscle protein fractional synthetic rate (FSR), muscle function tests, VO2peak, daily step count, dual energy x‐ray absorbometry (DEXA), 3‐day food diary, and blood biochemical analyses.ResultsThe best linear regressors of FSR were soluble fiber (R2=−0.59, P=0.03) and vitamin D intake (R2=0.60, P=0.01). The best multiple regressors were soluble fiber and leucine intake (R2=0.85, P=0.009). When the subjects were divided by BMI into overweight (n=4) or normal weight (n=4), the overweight subjects had a lower relative lean body weight (62.2±6.2% vs. 70.4±8.3) and slower 20‐meter load carry with weight time (11.4±2.2 sec vs. 10.9±1.1).SummaryIn a group of healthy older adults who are meeting their recommended nutritional requirements, dietary factors influence FSR. Further, overweight subjects have additional negative health and functional outcomes. This study was supported by NIH R01 AG030070 and P30 AG024832.

Cardiorespiratory Fitness and Attentional Control in the Aging Brain

A growing body of literature provides evidence for the prophylactic influence of cardiorespiratory fitness on cognitive decline in older adults. This study examined the association between cardiorespiratory fitness and recruitment of the neural circuits involved in an attentional control task in a group of healthy older adults. Employing a version of the Stroop task, we examined whether higher levels of cardiorespiratory fitness were associated with an increase in activation in cortical regions responsible for imposing attentional control along with an up-regulation of activity in sensory brain regions that process task-relevant representations. Higher fitness levels were associated with better behavioral performance and an increase in the recruitment of prefrontal and parietal cortices in the most challenging condition, thus providing evidence that cardiorespiratory fitness is associated with an increase in the recruitment of the anterior processing regions. There was a top-down modulation of extrastriate visual areas that process both task-relevant and task-irrelevant attributes relative to the baseline. However, fitness was not associated with differential activation in the posterior processing regions, suggesting that fitness enhances attentional function by primarily influencing the neural circuitry of anterior cortical regions. This study provides novel evidence of a differential association of fitness with anterior and posterior brain regions, shedding further light onto the neural changes accompanying cardiorespiratory fitness.

Successful physiological aging and episodic memory: A brain stimulation study

Functional neuroimaging studies have shown that younger adults tend to asymmetrically recruit specific regions of an hemisphere in an episodic memory task (Hemispheric Encoding Retrieval Asymmetry—HERA model). In older adults, this hemispheric asymmetry is generally reduced as suggested by the Hemispheric Asymmetry Reduction for OLDer Adults—HAROLD-model. Recent works suggest that while low-performing older adults do not show this reduced asymmetry, high-performing older adults counteract age-related neural decline through a plastic reorganization of cerebral networks that results in reduced functional asymmetry. However, the issue of whether high- and low-performing older adults show different degrees of asymmetry and the relevance of this process for counteracting aging have not been clarified. We used transcranial magnetic stimulation (TMS) to transiently interfere with the function of the dorsolateral prefrontal cortex (DLPFC) during encoding or retrieval of associated and non-associated word pairs. A group of healthy older adults was studied during encoding and retrieval of word pairs. The subjects were divided in two subgroups according to their experimental performance (i.e., high- and low-performing). TMS effects on retrieval differed according to the subject's subgroup. In particular, the predominance of left vs. right DLPFC effects during encoding, predicted by the HERA model, was observed only in low-performing older adults, while the asymmetry reduction predicted by the HAROLD model was selectively shown for the high-performing group. The present data confirm that older adults with higher memory performance show less prefrontal asymmetry as an efficient strategy to counteract age-related memory decline.

Learning and memory in amnestic mild cognitive impairment: Contribution of working memory

In addition to deficits in delayed recall, recent research suggests that participants with amnestic mild cognitive impairment (aMCI) demonstrate diminished use of strategic encoding strategies during learning. Few studies have explored the cognitive mechanisms underlying this deficit. The aim of this study was to investigate in aMCI whether components of working memory (executive attention--attention set-shifting, dividing and focusing attention; and episodic buffer functions--strategic retrieval and manipulation of information) predict strategic encoding strategies during learning (semantic clustering). Thirty-three participants with aMCI and 33 healthy older adults (HOA) were administered neuropsychological tests assessing word-list learning and working memory. The aMCI group demonstrated significant impairment in acquisition, retrieval of information, and decreased use of semantic clustering strategies. Use of semantic clustering in the aMCI group was not predicted by measures of executive attention or phonemic verbal fluency, but was predicted by semantic verbal fluency performance. In the HOA group, semantic clustering was strongly related to semantic verbal fluency. These findings suggest that in aMCI, diminished strategic encoding strategies during learning (semantic clustering) is selectively related to the strategic function of the episodic buffer, but only when in interaction with the manipulation and retrieval of semantic associations.

Correlation of Longitudinal Cerebrospinal Fluid Biomarkers With Cognitive Decline in Healthy Older Adults

Abnormal cerebrospinal fluid (CSF) biomarker levels predict development of Alzheimer disease with good accuracy and are thought to precede cognitive deterioration. To investigate whether changes in CSF biomarker levels over time in healthy older adults are associated with a concurrent decline in cognitive performance. Retrospective analysis of longitudinal CSF biomarker levels and clinical data. A combined academic dementia disorder research center and dementia clinic. Thirty-seven cognitively healthy older volunteers (mean age, 73 years). Longitudinal CSF total tau protein, hyperphosphorylated tau protein 181, and beta-amyloid(1-42) protein levels and cognitive assessments at baseline and at follow-up 4 years later. Low levels of CSF beta-amyloid(1-42) protein at follow-up were associated with decreased delayed word recall score on the Alzheimer Disease Assessment Scale-cognitive subscale (r(s) = -0.437, P < .01) and with slower results on A Quick Test of Cognitive Speed (r(s) = -0.540, P < .001). Individuals with a decrease during the 4-year study of 15% or more in CSF beta-amyloid(1-42) protein level performed worse on the Alzheimer Disease Assessment Scale-cognitive subscale delayed word recall (z = -2.18, P < .05) and A Quick Test of Cognitive Speed (z = -2.35, P < .05) at follow-up. An increase over time of 20% or more in CSF hyperphosphorylated tau protein 181 level correlated with slower results on A Quick Test of Cognitive Speed at follow-up (z = -2.13, P < .05). Furthermore, the presence of the APOE-epsilon4 (OMIM 107741) allele was associated with a greater longitudinal decrease in CSF beta-amyloid(1-42) protein level (chi(2) = 10.47, P < .05) and with a higher CSF total tau protein level at follow-up (chi(2) = 8.83, P < .05). No correlation existed between baseline CSF biomarker levels and baseline or follow-up cognitive scores. In this group of healthy older adults, changes in CSF biomarker levels previously associated with Alzheimer disease correlated with a decline in cognitive functions. Changes in CSF biomarker levels may identify early neurodegenerative processes of Alzheimer disease.

Language and spatial reorientation: Evidence from severe aphasia.

Investigating spatial cognition in individuals with acquired language impairments can inform our understanding of how components of language are involved in spatial representation. Using the reorientation paradigm of Hermer-Vazquez, Spelke, and Katsnelson (1999), we examined spatial cue integration (landmark-geometry conjunctions) in individuals with severe agrammatic or global aphasia and in a group of healthy older adults. Participants with aphasia performed similarly to healthy controls in the reorientation task, demonstrating the ability to integrate landmark and geometric cues, even during a concurrent verbal task designed to block access to any residual lexical resources. These results extend previous findings with healthy adults by suggesting that neither syntax nor lexicon is essential for spatial cue representation in a mature cognitive system, and provide further evidence that language deficits in aphasia can be independent from other domains of reasoning.

Manipulating task instructions to change narrative discourse performance

Background: A frequent method for eliciting narratives involves presenting picture stimuli and instructing the participant to “tell me what is happening in the picture(s) or tell me everything you see going on in the picture(s)”. It has been suggested that such instructions do not make an explicit request for providing temporal–causal information and so narrative samples frequently comprise listed information. Olness (2006) investigated the effect of task instruction on verb forms produced by adults with aphasia when describing pictures and found that using instructions that explicitly requested temporal–causal information—“Make up your own story about what happened, with a beginning, middle, and an end” (p. 179)—improved the ability of participants to convey the temporal–causal interrelationship depicted in single pictures. Further interpretation of the results was limited due to the lack of non‐brain‐injured participants for comparison. Aims: The purpose of the study was (1) to compare the performance of two groups of healthy older adults on the ability to convey main events in pictured stimuli when different task instructions were provided and (2) to quantify linguistic performance across the two groups and determine if groups significantly differed for any of the linguistic features. Method & Procedures: Participants included 24 healthy older adults assigned to one of two groups based on task instruction: picture description (PD) or storytelling (ST). Instructions were as follows—PD group: “Talk about what is going on in the picture(s)”; ST group: “I want you to look at the picture(s) and tell me a story that has a beginning, middle, and end”. Outcomes & Results: The ST group produced a significantly higher proportion of main events and significantly more past‐tense verbs than the PD group. Two significant relationships among the linguistic measures and main events measure were found for the PD group: a positive relationship between percent of information units (IUs) produced and proportion of main events for the sequential pictures and a negative relationship between D (Malvern & Richards, 1997) and proportion of main events for the single picture stimuli. Conclusions: Findings suggest that task instructions do affect the quality of the narrative produced by healthy older adults. The instructions to provide a story with a beginning, middle, and end may have acted as a scaffold for participants; cueing participants to provide the temporal–causal relationships depicted. Therefore, to better evaluate discourse production abilities in clinical populations, care should be taken in the task instructions provided.

Leukoaraiosis Severity and List-Learning in Dementia

In patients with dementia, leukoaraiosis (LA) was hypothesized to result in differential patterns of impairment on a verbal serial list-learning test. Using a visual rating scale, 144 dementia patients with ischemic scores <4 were re-categorized as having mild (n = 73), moderate (n = 44), or severe LA (n = 27). Mild LA was predicted to be associated with an amnestic list-learning profile, while severe LA was predicted to be associated with a dysexecutive profile. List-learning performances were standardized to a group of healthy older adults (n = 24). Analyses were conducted on a set of four factors derived from the list-learning paradigm, as well as error scores. Data indicate that LA severity is an important marker for understanding list learning in dementia.

Waist-Hip-Ratio as a Predictor of All-Cause Mortality in High-Functioning Older Adults

The relationship between obesity and mortality in older adults is debated, with concern that body mass index (BMI) may be an imperfect measure of obesity in this age group. We assessed the relationship between three measures of obesity and all-cause mortality in a group of healthy older adults. We analyzed data from the MacArthur Successful Aging Study, a longitudinal study of high-functioning men and women, ages 70-79 years at baseline. We examined 12-year, all-cause mortality risk by BMI, waist circumference, and waist-to-hip circumference ratio (WHR). Proportional hazards regression was used to adjust for gender, race, baseline age, and smoking status. We tested for obesity interactions with gender, race, and smoking status and conducted stratified analyses based on the results of interaction testing. There was no association between all-cause mortality and BMI or waist circumference in either unadjusted or adjusted analyses. In contrast, all-cause mortality increased with WHR. There was an interaction with sex, so that there was a graded relationship between WHR and mortality in women (relative hazard, 1.28 per 0.1 increase in WHR; 95% confidence interval, 1.05-1.55) and a threshold relationship in men (relative hazard 1.75 for WHR>1.0 compared to WHR< or =1.0; 95% confidence interval, 1.06-2.91). WHR rather than BMI appears to be the more appropriate yardstick for risk stratification of high-functioning older adults.