Predictors of Heterogeneity in Cognitive Function: APOE-e4, Sex, Education, Depression, and Vascular Risk.

OBJECTIVE: Mild cognitive impairment and dementia are clinically heterogeneous disorders influenced by diverse risk factors. Improved characterization of the effect of multiple risk factors influence on specific cognitive functions may improve understanding of mechanisms in early cognitive change and lead to more effective interventions. METHODS: Structural equation modeling (SEM) simultaneously examined the effects of modifiable (education, depression, and metabolic/vascular risk) and nonmodifiable risk factors (age, sex, and apolipoprotein E-ɛ4 allele [APOE-e4] status) on specific cognitive domains in 461 cognitively normal older adults. RESULTS: The hypothesized model(s) provided an adequate fit for the data. Sex differences in cognition, depression, and vascular risk were found. On average, men were higher in vascular risk with generally lower cognitive performance than women; women were more likely to have depression. APOE-e4 associated with depression but not age, sex, or metabolic/vascular risk. Depression associated with lower executive attention, memory, and language performance, whereas metabolic/vascular risk associated with lower executive attention, memory, and working memory. Older age and lower education are associated with worse performance across the cognitive domains. The combined risk factors accounted for 16%-47% of the variance in the cognitive domains. CONCLUSIONS: Results highlight the combined effect of risk factors on cognitive function. Future research is needed to determine whether the multifactorial risk effects on cognition vary by sex. Precision medicine approaches that integrate neuropsychological services may improve diagnostic accuracy and earlier identification of those at risk of cognitive decline.

Longitudinal assessment of neuropsychological and temporal/spatial gait characteristics of elderly fallers: taking it all in stride.

Gait abnormalities are linked to cognitive decline and an increased fall risk within older adults. The present study addressed gaps from cross-sectional studies in the literature by longitudinally examining the interplay between temporal and spatial aspects of gait, cognitive function, age, and lower-extremity strength in elderly "fallers" and "non-fallers". Gait characteristics, neuropsychological and physical test performance were examined at two time points spaced a year apart in cognitively intact individuals aged 60 and older (N = 416). Mixed-model repeated-measure ANCOVAs examined temporal (step time) and spatial (stride length) gait characteristics during a simple and cognitive-load walking task in fallers as compared to non-fallers. Fallers consistently demonstrated significant alterations in spatial, but not temporal, aspects of gait as compared to non-fallers during both walking tasks. Step time became slower as stride length shortened amongst all participants during the dual task. Shorter strides and slower step times during the dual task were both predicted by worse executive attention/processing speed performance. In summary, divided attention significantly impacts spatial aspects of gait in "fallers", suggesting stride length changes may precede declines in other neuropsychological and gait characteristics, thereby selectively increasing fall risk. Our results indicate that multimodal intervention approaches that integrate physical and cognitive remediation strategies may increase the effectiveness of fall risk interventions.

A longitudinal study on dual-tasking effects on gait: cognitive change predicts gait variance in the elderly.

Neuropsychological abilities have found to explain a large proportion of variance in objective measures of walking gait that predict both dementia and falling within the elderly. However, to this date there has been little research on the interplay between changes in these neuropsychological processes and walking gait overtime. To our knowledge, the present study is the first to investigate intra-individual changes in neurocognitive test performance and gait step time at two-time points across a one-year span. Neuropsychological test scores from 440 elderly individuals deemed cognitively normal at Year One were analyzed via repeated measures t-tests to assess for decline in cognitive performance at Year Two. 34 of these 440 individuals neuropsychological test performance significantly declined at Year Two; whereas the "non-decliners" displayed improved memory, working memory, attention/processing speed test performance. Neuropsychological test scores were also submitted to factor analysis at both time points for data reduction purposes and to assess the factor stability overtime. Results at Year One yielded a three-factor solution: Language/Memory, Executive Attention/Processing Speed, and Working Memory. Year Two's test scores also generated a three-factor solution (Working Memory, Language/Executive Attention/Processing Speed, and Memory). Notably, language measures loaded on Executive Attention/Processing Speed rather than on the Memory factor at Year Two. Hierarchal multiple regression revealed that both Executive Attention/Processing Speed and sex significantly predicted variance in dual task step time at both time points. Remarkably, in the "decliners", the magnitude of the contribution of the neuropsychological characteristics to gait variance significantly increased at Year Two. In summary, this study provides longitudinal evidence of the dynamic relationship between intra-individual cognitive change and its influence on dual task gait step time. These results also indicate that the failure to show improved test performance (particularly, on memory tests) with repeated administrations might prove to be useful of indicator of early cognitive decline.

Comparison of older adults' steps per day using NL-1000 pedometer and two GT3X+ accelerometer filters.

The purpose of this study was to compare the steps/d derived from the ActiGraph GT3X+ using the manufacturer's default filter (DF) and low-frequency-extension filter (LFX) with those from the NL-1000 pedometer in an older adult sample. Fifteen older adults (61-82 yr) wore a GT3X+ (24 hr/day) and an NL-1000 (waking hours) for 7 d. Day was the unit of analysis (n = 86 valid days) comparing (a) GT3X+ DF and NL-1000 steps/d and (b) GT3X+ LFX and NL-1000 steps/d. DF was highly correlated with NL-1000 (r = .80), but there was a significant mean difference (-769 steps/d). LFX and NL-1000 were highly correlated (r = .90), but there also was a significant mean difference (8,140 steps/d). Percent difference and absolute percent difference between DF and NL-1000 were -7.4% and 16.0%, respectively, and for LFX and NL-1000 both were 121.9%. Regardless of filter used, GT3X+ did not provide comparable pedometer estimates of steps/d in this older adult sample.

Steps per day, peak cadence, body mass index, and age in community-dwelling older adults.

PURPOSE: The relationships between demographic and anthropometric indices and older adults' quantity and quality of ambulatory activity are uncertain. We examined the relationship between accelerometer-determined steps per day (quantity) and peak 30-min cadence (quality; mean steps per minute recorded for the 30 highest, but not necessarily consecutive, minutes in a day) in community-dwelling older adults relative to sex, age, and body mass index (BMI). METHODS: Minute-by-minute accelerometer-determined step data for 5.8 ± 0.9 d were available for 100 women and 43 men (58-92 yr, BMI = 26.6 ± 4.2 kg·m). Sex-specific Spearman correlations compared steps per day with peak 30-min cadence and both to age and BMI. Partial correlations were computed controlling for 1) age, 2) BMI, 3) steps per day and age, or 4) steps per day and BMI. Significance was set at P < 0.05. RESULTS: Participants averaged 5605 ± 2588 steps per day with a peak 30-min cadence of 63.6 ± 24.6 steps per minute (mean ± SD). Correlations between these two variables were r = 0.883 (women) and r = 0.820 (men). Steps per day and peak 30-min cadence were significantly correlated with age (r = -0.442 and r = -0.327, respectively) and BMI (r = -0.248 and r = -0.286, respectively) in women. For men, steps per day and peak 30-min cadence were only significantly related to age (r = -0.665 and r = -0.381, respectively). Controlling for steps per day weakened all relationships with peak 30-min cadence to a point of nonsignificance with one exception: the partial correlation of age with peak 30-min cadence was weakened but remained significant (r = 0.335) after controlling for steps per day and BMI in men. CONCLUSIONS: The usefulness of peak 30-min cadence beyond steps per day is not apparent, at least in terms of sex, age, and BMI, and needs to be evaluated in larger and more diverse samples and against other parameters of interest, including those more theoretically linked to intensity of effort.

Preliminary comparison of clinical and free-living measures of stepping cadence in older adults.

BACKGROUND: The relationship between clinically assessed and free-living walking is unclear. Cadence (steps/min) can be measured accurately under both conditions using modern technologies, thus providing a common measurement metric. Therefore, the purpose of this study was to compare clinical and free-living cadence in older adults. METHODS: 15 community-dwelling older adults (7 men, 8 women; 61-81 years) completed GAITRite-determined normal and dual-task walks and wore objective monitors for 1 week. Descriptive data included gait speed (cm/sec), steps/day, as well as cadence. Nonparametric tests evaluated differences between normal and dual-task walks and between accelerometer- and pedometer-determined steps/day. Free-living time detected above clinically determined cadence was calculated. RESULTS: Participants crossed the GAITRite at 125.56 ± 15.51 cm/sec (men) and 107.93 ± 9.41 steps/min (women) during their normal walk and at 112.59 ± 17.90 cm/sec and 103.10 ± 1.30 steps/min during their dual-task walk (differences between walks P < .05). Overall, they averaged 7159 ± 2480 (accelerometer) and 7813 ± 2919 steps/day (pedometer; difference NS). On average, < 10 min/day was spent above clinically determined cadences. CONCLUSIONS: High-functioning, community-dwelling older adults are capable of walking at relatively high cadences (ie, > 100 steps/min). However, the same behavior appears to be uncommon in daily life, even for a minute.

Relationship between cognitive domains, physical performance, and gait in elderly and demented subjects.

Cognitive function declines with age, with studies linking decreases in cognitive function to increased fall risk. The association between declines in specific cognitive domains and the development of gait and physical performance deficits has not been established. The current cross-sectional study was designed to address these issues using well characterized control subjects (n = 50), and individuals with early stage dementia (n = 50) tightly matched for age, gender, and education. All participants received detailed cognitive assessments for global cognitive function, as well as for processing speed, verbal fluency, and executive function. Additionally, participants were administered single- and dual-task gait assessments (GAITRite) and Short Physical Performance Battery (SPPB) measures of physical performance (gait, balance, chair stands). Data show that all measures of cognitive function correlated significantly with measures of gait and physical performance when analyzed in all subjects or just subjects with dementia. However, data also reveal that measures of processing speed and verbal fluency correlated significantly with multiple aspects of motor performance in non-demented, control subjects, even when corrected for age. There was no correlation between global cognitive function and motor performance, and only limited relationship between executive function and motor performance in non-demented, control subjects. These studies reveal the complex interactions between cognitive function and gait/physical performance in the context of aging and dementia, and suggest that impairments in specific cognitive domains might undermine gait and physical performance and thus exacerbate fall risk in the elderly.

Memory for names test provides a useful confrontational naming task for aging and continuum of dementia.

There is an increasing need to develop new neuropsychometric tools sensitive enough to detect subtle declines in cognitive performance during normal aging, as well as to distinguish between normal aging and the earliest stages of dementia. In this study, we report our findings regarding a new confrontational naming test, the Memory for Names test. We conducted evaluations utilizing a cohort of 234 elderly participants who comprised a spectrum of cognitive function ranging from normal for age (Uniform Data Set Overall Appraisal = 2, Clinical Dementia Rating = 0) to demented (Clinical Dementia Rating = 1-2, Mini Mental Status Examination Total Score <25). The Memory for Names test was found to measure the same cognitive construct as the Boston Naming Test. In conclusion, the Memory for Names test is a reliable and valid measure of age-related cognitive function that can discriminate between normal aging and mild cognitive impairment, and between mild cognitive impairment and dementia.