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.

Examining Relationships between Multiple Self-Reported Sleep Measures and Gait Domains in Cognitively Healthy Older Adults.

BACKGROUND: Gait-related changes in older adulthood may be related to changes in cognition (e.g., executive functioning), and recent work suggests that different self-reported measures of sleep may be tied to contrasting aspects of executive functioning. However, the relationship between these self-reported sleep measures and gait domains has not been explored. Such an investigation would be useful in helping to determine which older adults might exhibit changes in gait as well as experience other gait-associated changes (e.g., increased fall risk). OBJECTIVE: To examine associations between different aspects of self-reported sleep and gait domains in a sample of cognitively healthy older adults. METHOD: A total of 423 older adults (mean age 69.9 years, range 50-92) completed self-report measures of sleep quality, daytime sleepiness, and sleep-related distress. The participants also completed an objective, electronic measure of both single-task and dual-task gait (i.e., GAITRite). Principal component analyses were used to elucidate the solution for each gait condition, and multiple linear regression was used to examine the contributions of sleep measures to variability in gait performance. RESULTS: A 5-component solution of the single-task condition and a 4-component solution of the dual-task condition were identified. Multiple linear regressions revealed that a poorer sleep quality was associated with greater single-task and dual-task asymmetry. Greater daytime sleepiness was associated with increased dual-task gait variability and postural control. After controlling for the effects of other facets of sleep, sleep-related distress was not associated with any gait domain. CONCLUSIONS: Among cognitively healthy older adults,sleep quality and daytime sleepiness, but not sleep-related distress, are associated with aspects of gait. Patients who report these symptoms should be assessed and monitored for possible changes in gait.

Understanding heterogeneity in older adults: Latent growth curve modeling of cognitive functioning.

BACKGROUND: Clarifying relationships between specific neurocognitive functions in cognitively intact older adults can improve our understanding of mechanisms involved in cognitive decline, which may allow identification of new opportunities for intervention and earlier detection of those at increased risk of dementia. METHOD: The present study employed latent growth curve modeling to longitudinally examine the relationship between executive attention/processing speed, episodic memory, language, and working memory functioning utilizing the neuropsychological test battery from the National Alzheimer's Disease Coordinating Center. A total of 691 relatively healthy older adults (Mage = 69.07, SD = 6.49) were assessed at baseline, and 553 individuals completed three visits spanning a two-year period. RESULTS: Better cognitive performance was concomitantly associated with better functioning across domains. Subtle declines in executive attention/processing speed processes were found, while, on average, memory and language performance improved with repeated testing. Lower executive attention/processing speed performance at baseline predicted less incremental growth rate in memory. In turn, higher initial memory functioning was associated with incremental improvements in language performance. CONCLUSIONS: These results are consistent with the notion that intact executive function and attention processes are important to preserving memory functioning with advanced age, but are also the functions most susceptible to decline with age. These findings also provide further insight into the critical role of practice effects in clinical assessment practice and have implications for pharmaceutical trials. Practice effects should be routinely considered as they may give the appearance of retention of function within the cognitive domains considered to be a hallmark of Alzheimer's disease pathology.

Reliability and Validity of a Novel Internet-Based Battery to Assess Mood and Cognitive Function in the Elderly.

Dementia is a chronic condition in the elderly and depression is often a concurrent symptom. As populations continue to age, accessible and useful tools to screen for cognitive function and its associated symptoms in elderly populations are needed. The aim of this study was to test the reliability and validity of a new internet-based assessment battery for screening mood and cognitive function in an elderly population. Specifically, the Helping Hand Technology (HHT) assessments for depression (HHT-D) and global cognitive function (HHT-G) were evaluated in a sample of 57 elderly participants (22 male, 35 female) aged 59-85 years. The study sample was categorized into three groups: 1) dementia (n = 8; Mini-Mental State Exam (MMSE) score 10-24), 2) mild cognitive impairment (n = 24; MMSE score 25-28), and 3) control (n = 25; MMSE score 29-30). Test-retest reliability (Pearson correlation coefficient, r) and internal consistency reliability (Cronbach's alpha, α) of the HHT-D and HHT-G were assessed. Validity of the HHT-D and HHT-G was tested via comparison (Pearson r) to commonly used pencil-and-paper based assessments: HHT-D versus the Geriatric Depression Scale (GDS) and HHT-G versus the MMSE. Good test-retest (r = 0.80; p < 0.0001) and acceptable internal consistency reliability (α= 0.73) of the HHT-D were established. Moderate support for the validity of the HHT-D was obtained (r = 0.60 between the HHT-D and GDS; p < 0.0001). Results indicated good test-retest (r = 0.87; p < 0.0001) and acceptable internal consistency reliability (α= 0.70) of the HHT-G. Validity of the HHT-G was supported (r = 0.71 between the HHT-G and MMSE; p < 0.0001). In summary, the HHT-D and HHT-G were found to be reliable and valid computerized assessments to screen for depression and cognitive status, respectively, in an elderly sample.

Apolipoprotein E Genotype Linked to Spatial Gait Characteristics: Predictors of Cognitive Dual Task Gait Change.

BACKGROUND: Developing measures to detect preclinical Alzheimer's Disease is vital, as prodromal stage interventions may prove more efficacious in altering the disease's trajectory. Gait changes may serve as a useful clinical heuristic that precedes cognitive decline. This study provides the first systematic investigation of gait characteristics relationship with relevant demographic, physical, genetic (Apolipoprotein E genotype), and health risk factors in non-demented older adults during a cognitive-load dual task walking condition. METHODS: The GAITRite system provided objective measurement of gait characteristics in APOE-e4 "carriers" (n = 75) and "non-carriers" (n = 224). Analyses examined stride length and step time gait characteristics during simple and dual-task (spelling five-letter words backwards) conditions in relation to demographic, physical, genetic, and health risk factors. RESULTS: Slower step time and shorter stride length associated with older age, greater health risk, and worse physical performance (ps < .05). Men and women differed in height, gait characteristics, health risk factors and global cognition (ps < .05). APOE-e4 associated with a higher likelihood of hypercholesterolemia and overall illness index scores (ps < .05). No genotype-sex interactions on gait were found. APOE-e4 was linked to shorter stride length and greater dual-task related disturbances in stride length. CONCLUSIONS: Stride length has been linked to heightened fall risk, attention decrements and structural brain changes in older adults. Our results indicate that stride length is a useful behavioral marker of cognitive change that is associated with genetic risk for AD. Sex disparities in motor decline may be a function of health risk factors.

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.

Feasibility, reliability, and validity of a smartphone based application for the assessment of cognitive function in the elderly.

While considerable knowledge has been gained through the use of established cognitive and motor assessment tools, there is a considerable interest and need for the development of a battery of reliable and validated assessment tools that provide real-time and remote analysis of cognitive and motor function in the elderly. Smartphones appear to be an obvious choice for the development of these "next-generation" assessment tools for geriatric research, although to date no studies have reported on the use of smartphone-based applications for the study of cognition in the elderly. The primary focus of the current study was to assess the feasibility, reliability, and validity of a smartphone-based application for the assessment of cognitive function in the elderly. A total of 57 non-demented elderly individuals were administered a newly developed smartphone application-based Color-Shape Test (CST) in order to determine its utility in measuring cognitive processing speed in the elderly. Validity of this novel cognitive task was assessed by correlating performance on the CST with scores on widely accepted assessments of cognitive function. Scores on the CST were significantly correlated with global cognition (Mini-Mental State Exam: r = 0.515, p<0.0001) and multiple measures of processing speed and attention (Digit Span: r = 0.427, p<0.0001; Trail Making Test: r = -0.651, p<0.00001; Digit Symbol Test: r = 0.508, p<0.0001). The CST was not correlated with naming and verbal fluency tasks (Boston Naming Test, Vegetable/Animal Naming) or memory tasks (Logical Memory Test). Test re-test reliability was observed to be significant (r = 0.726; p = 0.02). Together, these data are the first to demonstrate the feasibility, reliability, and validity of using a smartphone-based application for the purpose of assessing cognitive function in the elderly. The importance of these findings for the establishment of smartphone-based assessment batteries of cognitive and motor function in the elderly is discussed.

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.