Multidimensional predictors of fatigue among octogenarians and centenarians.

BACKGROUND: Fatigue is a common and frequently observed complaint among older adults. However, knowledge about the nature and correlates of fatigue in old age is very limited. OBJECTIVE: This study examined the relationship of functional indicators, psychological and situational factors and fatigue for 210 octogenarians and centenarians from the Georgia Centenarian Study. METHODS: Three indicators of functional capacity (self-rated health, instrumental activities of daily living, physical activities of daily living), two indicators of psychological well-being (positive and negative affect), two indicators of situational factors (social network and social support), and a multidimensional fatigue scale were used. Blocked multiple regression analyses were computed to examine significant factors related to fatigue. In addition, multi-group analysis in structural equation modeling was used to investigate residential differences (i.e., long-term care facilities vs. private homes) in the relationship between significant factors and fatigue. RESULTS: Blocked multiple regression analyses indicated that two indicators of functional capacity, self-rated health and instrumental activities of daily living, both positive and negative affect, and social support were significant predictors of fatigue among oldest-old adults. The multiple group analysis in structural equation modeling revealed a significant difference among oldest-old adults based on residential status. CONCLUSION: The results suggest that we should not consider fatigue as merely an unpleasant physical symptom, but rather adopt a perspective that different factors such as psychosocial aspects can influence fatigue in advanced later life.

Life events and personality predicting loneliness among centenarians: findings from the Georgia Centenarian Study.

Regarding the purpose of this study, the researchers analyzed the roles that both life events (life-time positive events and life-time negative events) and personality (Neuroticism, Extraversion, Trust, Competence, and Ideas) played in participants of the Georgia Centenarian Study. The researchers analyzed these variables to determine whether they predicted loneliness. Analyses indicated that life-time negative events significantly predicted loneliness. In essence, the higher was the number of life-time negative life events, the higher was the loneliness score. Moreover, Neuroticism, Competence, and Ideas were all significant predictors of loneliness. The higher was the level of Neuroticism and intellectual curiosity, the higher was the level of loneliness, whereas the lower was the level of Competence, the higher was the level of loneliness. In addition, both life-time positive and life-time negative life events were significant predictors of Neuroticism. The higher was the number of life-time positive events, the lower was the level of Neuroticism, and the higher was the number of life-time negative events, the greater was the level of Neuroticism. These results indicated that life-time negative events indirectly affect loneliness via Neuroticism. Last, our results indicated that the Competence facet mediated the relationship between lifetime negative life events and loneliness. Life-time negative life events significantly affected centenarians' perceived competence, and Competence in turn significantly affected the centenarians' loneliness. These results as a whole not only add to our understanding of the link between personality and loneliness, but also provide new insight into how life events predict loneliness.

Brain Α-Tocopherol Concentration is Inversely Associated with Neurofibrillary Tangle Counts in Brain Regions Affected in Earlier Braak Stages: A Cross-Sectional Finding in the Oldest Old.

Objectives: Higher vitamin E status has been associated with lower risk of Alzheimer's disease (AD). However, evidence of the association of vitamin E concentration in neural tissue with AD pathologies is limited. Design: The cross-sectional relationship between the human brain concentrations of α- and γ-tocopherol and the severity of AD pathologies - neurofibrillary tangle (NFT) and neuritic plaque (NP) - was investigated. Setting & Participants: Brains from 43 centenarians (≥ 98 years at death) enrolled in the Phase III of the Georgia Centenarian Study were collected at autopsy. Measurements: Brain α- and γ-tocopherol concentrations (previously reported) were averaged from frontal, temporal, and occipital cortices. NP and NFT counts (previously reported) were assessed in frontal, temporal, parietal, entorhinal cortices, amygdala, hippocampus, and subiculum. NFT topological progression was assessed using Braak staging. Multiple linear regression was performed to assess the relationship between tocopherol concentrations and NP or NFT counts, with and without adjustment for covariates. Results: Brain α-tocopherol concentrations were inversely associated with NFT but not NP counts in amygdala (ß = -2.67, 95% CI [-4.57, -0.79]), entorhinal cortex (ß = -2.01, 95% CI [-3.72, -0.30]), hippocampus (ß = -2.23, 95% CI [-3.82, -0.64]), and subiculum (ß = -2.52, 95% CI [-4.42, -0.62]) where NFT present earlier in its topological progression, but not in neocortices. Subjects with Braak III-IV had lower α-tocopherol (median = 69,622 pmol/g, IQR = 54,389-72,155 pmol/g) than those with Braak I-II (median = 72,108 pmol/g, IQR = 64,056-82,430 pmol/g), but the difference was of borderline significance (p = 0.063). γ-Tocopherol concentrations were not associated with either NFT or NP counts in any brain regions assessed. Conclusions: Higher brain α-tocopherol level is specifically associated with lower NFT counts in brain structures affected in earlier Braak stages. Our findings emphasize the possible importance of α-tocopherol intervention timing in tauopathy progression and warrant future clinical trials.

Semantic memory activation in amnestic mild cognitive impairment.

Cognitively intact older individuals at risk for developing Alzheimer's disease frequently show increased functional magnetic resonance imaging (fMRI) brain activation presumably associated with compensatory recruitment, whereas mild cognitive impairment (MCI) patients tend not to show increased activation presumably due to reduced neural reserve. Previous studies, however, have typically used episodic memory activation tasks, placing MCI participants at a performance disadvantage relative to healthy elders. In this event-related fMRI study, we employed a low effort, high accuracy semantic memory task to determine if increased activation of memory circuits is preserved in amnestic MCI when task performance is controlled. Fifty-seven participants, aged 65-85 years, comprised three groups (n = 19 each): amnestic MCI patients; cognitively intact older participants at risk for developing Alzheimer's disease based on having at least one ApoE epsilon4 allele and a positive family history of Alzheimer's disease (At Risk); and cognitively intact participants without Alzheimer's disease risk factors (Control). fMRI was conducted on a 3T MR scanner while participants performed a famous name discrimination task. Participants also underwent neuropsychological testing outside the scanner; whole brain and hippocampal atrophy were assessed from anatomical MRI scans. The three groups did not differ on demographic variables or on fame discrimination performance (>87% correct for all groups). As expected, the amnestic MCI participants demonstrated reduced episodic memory performance. Spatial extent of activation (Fame--Unfamiliar subtraction) differentiated the three groups (Control = 0 ml, At Risk = 9.7 ml, MCI = 34.7 ml). The MCI and At Risk groups showed significantly greater per cent signal change than Control participants in 8 of 14 functionally defined regions, including the medial temporal lobe, temporoparietal junction, and posterior cingulate/precuneus. MCI participants also showed greater activation than Controls in two frontal regions. At Risk, but not MCI, participants showed increased activity in the left hippocampal complex; MCI participants, however, evidenced increased activity in this region when hippocampal atrophy was controlled. When performance is equated, MCI patients demonstrate functional compensation in brain regions subserving semantic memory systems that generally equals or exceeds that observed in cognitively intact individuals at risk for Alzheimer's disease. This hyperactivation profile in MCI is even observed in the left hippocampal complex, but only when the extent of hippocampal atrophy is taken into consideration.

Family history and adaptation among centenarians and octogenarians.

BACKGROUND: The purpose of this study was to analyze various 'family history' variables (i.e. childhood health, financial situation while growing up, living with grandparents before age 17, and number of children) among participants of the Georgia Centenarian Study. OBJECTIVE: To determine whether family history variables predict critical outcome areas such as cognitive functioning, activities of daily living, mental health, and economic dependence. METHODS: A total of 318 older adults (236 centenarians and 82 octogenarians) were assessed with regard to their mental status, ADL (activities of daily living) functioning, depression, family history, loneliness, and perceived economic status. RESULTS: Analyses indicated that the number of children significantly predicted the ability to engage in activities of daily living and loneliness. In essence, the more children, the higher the activities of the daily living score and the lower the loneliness scores. In addition, childhood health significantly predicted loneliness. The poorer one's health in childhood, the higher the loneliness scores. CONCLUSION: The results of this study confirm the importance of distal family history variables on present-day functioning.

Predicting happiness among centenarians.

BACKGROUND: Happiness is believed to evolve from the comparison of current circumstances relative to past achievement. However, gerontological literature on happiness in extreme old age has been limited. OBJECTIVE: The purpose of this study was to determine how perceptions of health, social provisions, and economics link past satisfaction with life to current feelings of happiness among persons living to 100 years of age and beyond. METHODS: A total of 158 centenarians from the Georgia Centenarian Study were included to conduct the investigation. Items reflecting congruence and happiness from the Life Satisfaction Index were used to evaluate a model of happiness. Pathways between congruence, perceived economic security, subjective health, perceived social provisions, and happiness were analyzed using structural equation modeling. RESULTS: Congruence emerged as a key predictor of happiness. Furthermore, congruence predicted perceived economic security and subjective health, whereas perceived economic security had a strong influence on subjective health status. CONCLUSION: It appears that past satisfaction with life influences how centenarians frame subjective evaluations of health status and economic security. Furthermore, past satisfaction with life is directly associated with present happiness. This presents implications relative to understanding how perception of resources may enhance quality of life among persons who live exceptionally long lives.

Distal and proximal resource influences on economic dependency among the oldest old.

BACKGROUND: As exceptional survivors, centenarians may have characteristics that reduce their dependency on family and community support systems despite the expectation that their extreme age creates a burden on those systems. The Georgia Centenarian Study obtained information about assistance for income, medical care, and caregiving of all types for a sample of centenarians and octogenarians. Previous studies have not established which characteristics may contribute to economic dependency among the oldest old. OBJECTIVE: To identify distal and proximal resource influences on economic dependency, considering past lifestyle, proximal health, economic resources, personality, and coping behavior. METHODS: Analysis sample sizes ranged from 109 to 138 octogenarians and centenarians. Blockwise multiple regressions predicted whether they received income assistance, number of medical care events, number of caregiving types, and total caregiving hours. RESULTS: Past life style, gender, ethnicity, socioeconomic status, functional health, and coping were not related to economic dependency. With the exception of the number of types of care, centenarians were not more dependent than octogenarians. Cognitive ability had the strongest effects for medical care and caregiving services. 'Extraversion', 'ideas', 'neuroticism', and 'competence' personality factors had significant effects for caregiving types and total hours of care received. CONCLUSION: Monitoring and intervention to maintain cognitive ability are critical practices for autonomy and reduced economic dependency among the oldest old. Psychological resources are more important influences on social support than functional health and other proximal economic resources.

Social resources and longevity: findings from the Georgia centenarian study.

BACKGROUND: As the proportion of adults aged 85 and older increases, investigations of resources essential for adapting to the challenges of aging are required. OBJECTIVE: To comprehensively investigate the social resources of cognitively intact centenarians participating in the Georgia Centenarian Study and the association between these resources and residence status. METHODS: Two widely used measures of social resources were investigated among participants living in private homes, personal care facilities, and nursing homes. Logistic regression was used to determine significant predictors of nursing home residence. RESULTS: Differences in levels of social resources were found between centenarians and octogenarians, and among centenarians in different living situations. Analyses revealed differential findings between self- and proxy reports. Controlling for education, activities of daily living, and financial ability to meet needs, only one of the two social resources measures significantly reduced the odds of nursing home residence. CONCLUSION: The findings of this study add to the existing literature on one of the basic adaptive resources (social resources) for centenarians. Whether a more specific assessment of network contact is employed, or a more global assessment is used, differences in these constructs exist between centenarians and octogenarians, among centenarians in differing living conditions, and across types of informants. Researchers examining the different resources that may contribute to extraordinary longevity and positive adaptation may find it essential to differentiate between the oldest old and centenarians, and to account for differences based upon measure, reporter type, and centenarian residence status.

Butanol is superior to water for performing positron emission tomography activation studies.

[15(O)]Butanol has been shown to be superior to [15(O)]water for measuring cerebral blood flow with positron emission tomography. This work demonstrates that it is also superior for performing activation studies. Data were collected under three conditions: a visual confrontation animal-naming task, nonsense figure size discrimination, and a nonvisual darkroom control task. Time-activity curves (TAC) were obtained for regions known to be activated by the confrontation naming task to compare absolute uptake and the different kinetics of the two tracers. Also, t statistic maps were calculated from the data of 10 subjects for both tracers and compared for magnitude of change and size of activated regions. Peak uptake in the whole-brain TAC were similar for the two tracers. For all regions and conditions, the washout rate of [15(O)]butanol was 41% greater than that of [15(O)]water. At a threshold of 0, the [15(O)]water and [15(O)]butanol percent difference (nonnormalized) and t statistic (global normalization) images are nearly identical, indicating that the same property is being measured with both tracers. The [15(O)]butanol parametric images displayed at a threshold of /t/ = 5 look similar to the [15(O)]water parametric maps displayed at a threshold of /t/ = 4, which is consistent with the observation that t statistic values in [15(O)]butanol images are generally greater. The t statistic values were equal when the [15(O)]butanol parametric map was created from any subset of 6 subjects and the [15(O)]water parametric map was created from all 10 subjects. Fewer subjects need to be studied with [15(O)]butanol to reach the same statistical power as an [15(O)]water-based study.

Repetitive transcranial magnetic stimulation does not replicate the Wada test.

The authors compared inferior frontal speech arrest from repetitive transcranial magnetic stimulation (rTMS) with bilateral Wada tests in 17 epilepsy surgery candidates. Although rTMS lateralization correlated with the Wada test in most subjects, rTMS also favored the right hemisphere at a rate significantly greater than the Wada test. Postoperative language deficits were more consistent with Wada results. Available methods for inducing speech arrest with rTMS do not replicate the results of Wada tests.

Functional outcome of cognitively impaired hip fracture patients on a geriatric rehabilitation unit.

OBJECTIVES: To compare outcomes (physical functions and discharge destinations) of cognitively impaired and intact older hip fracture patients, and to identify cognitive skills related to functional gains. DESIGN: Prospective longitudinal study of hip fracture patients treated on an acute inpatient rehabilitation service, with evaluation of functional performance and living status determined at admission and discharge. SETTING: A specialized inpatient geriatric rehabilitation program at Wesley Woods Geriatric Hospital, which is affiliated with Emory University School of Medicine. SUBJECTS: Fifty-eight hip fracture patients, 35 with and 23 without cognitive impairment. MEASUREMENTS: Cognitive functioning measured by the Mattis Dementia Rating Scale (MDRS); functional outcome assessed by the Functional Independence Measure (FIM); comparison of pre-fracture with discharge living environments. MAIN RESULTS: Both cognitively impaired and intact hip fracture patients exhibited similar overall FIM motor improvements as well as functional gains in specific FIM areas measuring self-care, sphincter control, and locomotion (e.g., walking). Cognitively intact patients, however, displayed significantly greater gains in mobility (e.g., transfers) at discharge. Cognitively impaired patients who lived in the community were as likely as intact patients to return to the community. Patients who entered the program at a modified dependence level (FIM 3-5) and achieved motor independence at discharge (FIM 6-7) had higher MDRS initiation/ perseveration and memory scores. CONCLUSIONS: Hip fracture patients with cognitive impairments can achieve positive outcomes as defined by functional improvement and discharge destination. Intensive post-fracture rehabilitation in the early phase of recovery may promote functional independence and a return to the community for older patients at risk for nursing home placement. Future research should examine the long-term maintenance of these improvements and explore how rehabilitation interventions can be altered to enhance outcome.

Using a computer model to explore impairments of acquisition processes following ingestion of diazepam.

Hypotheses about the information processes impaired in diazepam-induced amnesia were tested by fitting the output from a computer simulation of list learning to observed serial position curves and to overt rehearsal protocols. Twenty-four subjects received an average weight-relative dosage of 0.18 mg/kg oral diazepam; 24 subjects received placebo. Immediate free recall of 16-word lists was examined at 2- and 8-s presentation times. Subjects receiving diazepam recalled significantly fewer words than placebo subjects (diazepam = 6.77 +/- 2.39 words; placebo = 9.29 +/- 1.42 words); their memory impairment was greater at the 8-s than 2-s presentation time. Tests of nonlinear regression models based on computer simulations of list learning performance were consistent with the hypothesis that diazepam reduces rehearsal capacity and disrupts the formation or utilization of contextual and inter-item associations. Among these causes of diazepam-induced amnesia, the disruption of contextual associations appears most important. The results further suggest that quantitative modeling of memory data may complement traditional methods of inferring relationships between brain processes and cognitive dysfunction in amnesic states.

Examination of age-related deficits on the Wisconsin Card Sorting Test.

Adult age differences in Wisconsin Card Sorting Test (WCST) measures were examined before and after statistical control of age-related differences in measures of feedback usage, working memory, and perceptual-comparison speed. The proportion of age-related variance associated with a summary measure of WCST performance was greatly reduced after controlling for measures of feedback usage, working memory, and perceptual-comparison speed. Furthermore, the age-related variance associated with the feedback-usage measure was reduced after controlling for working memory and perceptual-comparison speed measures. These results are consistent with the idea that age-related performance differences in the WCST are partially mediated by adult age differences in feedback usage and that age differences in feedback usage are mediated by age differences in working memory, which are in turn-mediated by age-related reductions in processing speed, indexed by measures of perceptual-comparison speed.

Compensatory recruitment of neural resources during overt rehearsal of word lists in Alzheimer's disease.

Functional neuroanatomical correlates subserving maintenance rehearsal relative to a reading control task were investigated with positron emission tomography imaging of cerebral blood flow in 6 healthy older participants and 6 patients with mild Alzheimer's disease (AD). Rehearsal and reading rates and number of unique words rehearsed did not differ significantly for the 2 groups. The right dorsolateral prefrontal cortex was activated in both groups during rehearsal, highlighting this region's role in short-term maintenance of verbal information. A shift in cortical processing resources to more anterior brain regions with increased rehearsal list length was seen, likely reflecting greater demands on frontal cortex as cognitive load grows. Whereas controls showed unilateral right frontal activation during rehearsal, AD patients demonstrated bilateral frontal activation, possibly reflecting compensatory recruitment of neural resources.

Factor structure of the negative symptom assessment.

The factor structure of the Negative Symptom Assessment (NSA), a standardized negative symptoms rating scale, was systematically evaluated in a group of 223 inpatients with schizophrenia. Confirmatory factor analyses found that a six-factor model best described the NSA. More specifically, the domains of Communication, Emotion/Affect, Social Involvement, Motivation, Gross Cognition, and Retardation characterized the rating scale. This latent structure of the NSA is consistent with a multidimensional conceptualization of negative symptoms.

Development of a computer-based battery designed to screen adults for neuropsychological impairment.

The initial step in the development of a new computer-based neuropsychological testing system is described. A new hardware-software system and a screening battery consisting of an orientation task and five cognitive tests has been implemented. This novel screening battery is designed for use in identifying individuals among exposed groups who may require more extensive follow-up neuropsychological evaluation. Sophisticated, but currently available, and relatively inexpensive hardware and software technology are employed, introducing an improvement over existing computer-based batteries. Use of a digitized speech production device for producing instructions facilitates testing of illiterate subjects, use of auditory stimulus materials, and relatively easy translation of the testing instructions to other languages. Use of a pen-based notebook computer enables responding by the subject in a manner that is both natural and analogous to that used in existing paper-and-pencil testing instruments. Five neuropsychological tests were developed to cover a range of cognitive domains: 1) verbal list learning and recognition memory, 2) visual memory span, 3) conceptual and motor tracking, 4) psychomotor speed and accuracy, and 5) delayed verbal recognition. The screening instrument has been pilot-tested for feasibility of use among outpatients at an occupational medicine clinic and among community-dwelling older adults. This instrument is intended to provide a standardized efficient, cost-effective method for widespread use in occupational medicine and public health to detect and track subclinical neurotoxic effects and to prevent additional harmful exposure. Additional aspects of development of the computer-based testing system are discussed.

An analysis of test bias and differential item functioning due to race on the Mattis Dementia Rating Scale.

The Mattis Dementia Rating Scale (MDRS) is a commonly used cognitive measure designed to assess the course of decline in progressive dementias. However, little information is available about possible systematic racial bias on the items presented in this test. We investigated race as a potential source of test bias and differential item functioning in 40 pairs of African American and Caucasian dementia patients (N = 80), matched on age, education, and gender. Principal component analysis revealed similar patterns and magnitudes across component loadings for each racial group, indicating no clear evidence of test bias on account of race. Results of an item analysis of the MDRS revealed differential item functioning across groups on only 4 of 36 items, which may potentially be dropped to produce a modified MDRS that may be less sensitive to cultural factors. Given the absence of test bias because of race, the observed racial differences on the total MDRS score are most likely associated with group differences in dementia severity. We conclude that the MDRS shows no appreciable evidence of test bias and minimal differential item functioning (item bias) because of race, suggesting that the MDRS may be used in both African American and Caucasian dementia patients to assess dementia severity.

Controlled and automatic forms of memory and attention: process purity and the uniqueness of age-related influences.

Estimates of controlled and automatic processes hypothesized to underlie performance in a memory task and in an attention task were derived for 115 participants from 18 to 78 years of age using the process-dissociation procedure. Participants also performed speed and neuropsychological tests that were suspected to be negatively related to age. Process estimates showed good reliability (from .76 to .98), and the qualitative distinction between processes was supported by the overall pattern of correlations among measures. However, only estimated automatic processes exhibited unique variance, as they were either weakly related or unrelated both to performance on the other tests and to each other. Estimates of the control processes, in contrast, shared considerable variance with measures from other tests, and there were no unique, or independent, age-related effects on these measures. The results highlight the need to distinguish between process purity and the uniqueness of age-related influences in accounting for age differences in cognition.

Parsimonious prediction of Wechsler Memory Scale--III memory indices.

Equations for prorating the Wechsler Memory Scale--III (WMS-III) Index scores were derived and validated on a sample of 252 mixed clinical cases. Regression equations were performed using age-scaled scores as predictors and the sum of age-scaled scores for Immediate Memory (IM) and General Memory (GM) as the criteria. Including Logical Memory and Verbal Paired Associates with either Faces or Family Pictures resulted in estimated scores that accounted for 95% to 97% of the variance for IM and GM. Over 80% of these cases had estimated sum of scaled scores that fell within 3 points of actual sum of scaled scores, within 1 standard error of measurement. When only Logical Memory and Verbal Paired Associates were included, estimations accounted for only 87% of the variance, and only 60% of the estimated scores fell within 3 points of actual sum of scaled scores. The regression equations are presented, as are the confidence intervals derived from a bootstrapping procedure that created 15,000 different samples.

Cross-validation of prediction equations for Wechsler Memory Scale-III Indexes.

Six prediction equations were previously found to predict to Wechsler Memory Scale-III (WMS-3) Immediate Memory Index (IM) and General Memory Index (GM) using two- or three-subtest combinations. The equations were cross-validated on a sample of 214 mixed clinical patients from an entirely different location in the Midwest. The two three-subtest prediction equations (including Logical Memory, Verbal Paired Associates, and either Faces or Family Pictures) better estimated IM and GM than did the two-subtest equations (Logical Memory and Verbal Paired Associates). Correlations for the former equations correlated .97 and .96 with full WMS-3 IM and GM, respectively. In addition, at least 95% of the predicted scores were within two SEMs of obtained IM and GM scores. The two-subtest equations correlated only .89 for IM and .92 for GM. The predicted scores that fell within two SEMs captured 78% and 88% of the cases for IM and GM, respectively. The results provide support for the use of the three-subtest prorated forms of the WMS-3 to estimate IM and GM.