Brain donation and neuropathological examination of brain tissues is the only way to obtain definitive diagnostic information on research subjects enrolled in aging studies. We investigated predictors of brain donation in a population-based study of centenarians in Phase III of the Georgia Centenarian Study (GCS).
Sixty-six individuals (mean age = 100.6 years, 91% female, 20% African American) were successfully recruited from the core sample of 244 individuals residing in 44 counties of Northeast Georgia to provide brain donation.
Bivariate (t-tests, chi-square tests) and multivariate analyses (logistic regression) showed no significant differences between donors and non-donors across a wide range of demographic, religious, personality, cognitive and physical functioning characteristics.
We succeeded in recruiting a diverse, population-based sample of centenarians for brain donation. Our findings also suggest that barriers to brain donation reported in other studies may have less impact in these exceptional survivors.
Many forms of cancer present with a complex metabolic profile characterised by loss of lean body mass known as cancer cachexia. The physical impact of cachexia contributes to decreased patient quality of life, treatment success and survival due to gross alterations in protein metabolism, increased oxidative stress and systemic inflammation. The psychological impact also contributes to decreased quality of life for both patients and their families. Combination therapies that target multiple pathways, such as eicosapentaenoic acid administered in combination with exercise, appetite stimulants, antioxidants or anti-inflammatories, have potential in the treatment of this complex syndrome and require further development.
Cancer cachexia; Oxidative stress; Antioxidant; Eicosapentaenoic acid; Oxypurinol
Phosphatidylinositol-3-kinase (PI3K) signaling is constitutive in most human cancers. Selective inhibition of PI3Kδ (p110δ) by GS-1101 has emerged as a promising therapy in chronic lymphocytic leukemia and indolent lymphomas. In aggressive non-Hodgkin lymphomas such as mantle cell lymphoma (MCL), however, efficacy has been observed, but the extent and duration of tumor control is modest. To determine if tumor killing by GS-1101 is cell cycle-dependent, we show in primary MCL cells by whole-transcriptome sequencing that, despite aberrant expression and recurrent mutations in Cyclin D1, mutations are rare in coding regions of CDK4, RB1 and other genes that control G1-S cell cycle progression or PI3K/AKT signaling. PI3Kδ is the predominant PI3K catalytic subunit expressed, and inhibition by GS-1101 transiently inhibits AKT phosphorylation but not proliferation in MCL cells. Induction of prolonged early G1-arrest (pG1) by selective inhibition of CDK4/CDK6 with PD 0332991 amplifies and sustains PI3Kδ inhibition, which leads to robust apoptosis. Accordingly, inhibition of PI3Kδ induces apoptosis of primary MCL tumor cells once they have ceased to cycle ex vivo, and this killing is enhanced by PD 0332991 inhibition of CDK4/CDK6. PIK3IP1, a negative PI3K regulator, appears to mediate pG1 sensitization to PI3K inhibition; it is markedly reduced in MCL tumor cells compared with normal peripheral B cells, profoundly induced in pG1 and required for pG1 sensitization to GS-1101. Thus, the magnitude and duration of PI3K inhibition and tumor killing by GS-1101 is pG1-dependent, suggesting induction of pG1 by CDK4/CDK6 inhibition as a strategy to sensitize proliferating lymphoma cells to PI3K inhibition.
CDK4; CDK6; GS-1101; PD 0332991; PI3Kα; PI3Kδ; PIK3IP1; mantle cell lymphoma
In Europe peatlands are wetlands of postglacial origin. Because of climatic changes and agricultural activities (i.e. drainage and peat extraction), they are one of the most endangered ecosystems worldwide. Water mites are well known as indicators of changing environments in other ecosystems such as springs and lakes. For our study we selected seven peatlands located in North-Western Poland and focused on water mite distribution and associated habitat and water quality variables. We described water mite fauna in various microhabitats (aquatic and semiaquatic) along the mineral-richness gradient to test whether this gradient is reflected in the composition of water mite assemblages. We selected conductivity, pH and vegetation as variables reflecting the poor-rich gradient. Additionally, we measured water depth, temperature and dissolved oxygen, which are often important parameters for water mites. We also noted presence of prey and host taxa of particular water mite species. Based on physicochemical parameters we identified three types of habitats harbouring three distinctive species groups of water mites. We were able to distinguish species that appear to be typical of spring fens (e.g. Hygrobates norvegicus, Lebertia separata), connected with acidic, nutrient poor pools (e.g. Arrenurus neumani, A. pustulator) and species seemingly typical of temporary habitats dominated by Sphagnum mosses (e.g. Piersigia intermedia, Zschokkea oblonga, A. stecki). The poor-rich gradient is strongly reflected in the composition of water mite assemblages. We also found strong correlations between the water mite fauna and both conductivity and pH gradient. Our results show that water conductivity is the most important of the examined factors, driving mite-species distribution in peatlands.
Peatlands; Spring fen; Habitat; Sphagnum; Poor-rich gradient; Vegetation; Acidification
Sphingolipids serve an important role as effector molecules in signaling pathways bearing on apoptosis and cell survival. The balance between proapoptotic ceramide and prosurvival sphingosine-1-phosphate, sometimes termed the “sphingolipid rheostat,” has received particular attention. Less well studied is the role of the follicular lymphoma variant translocation 1 (FVT1) gene, which was identified through its involvement in an atypical follicular lymphoma translocation and which encodes an enzyme in the synthetic pathway of ceramide. We investigated the expression of FVT1 in a variety of B-cell non-Hodgkin lymphomas and found that FVT1 is significantly underexpressed by germinal center–type diffuse large B-cell lymphoma (DLBCL) when compared with non–germinal center–type DLBCL, follicular lymphoma, and normal tonsil control samples. Increased expression of FVT1 correlated with decreased survival, suggesting that changes in the expression of FVT1 and in the concentrations of bioactive sphingolipids may be important in the pathogenesis and treatment of some types of DLBCL.
Follicular lymphoma variant translocation 1 gene; FVT1; Lymphoma; Sphingolipids; Ceramide
The goals of this article are to (a) establish the concurrent and clinical validity of the Global Deterioration scale in assessing cognitive functions and stages of dementia among centenarians, (b) identify the prevalence of all-cause dementia in representative samples of centenarians, and (c) demonstrate how variations in sample demographic characteristics could significantly affect estimates of dementia prevalence. A quarter of the 244 centenarians in a population-based sample had no objective evidence of memory deficits. Another quarter showed signs of transient confusion, and about half showed classical behavioral signs of dementia with about 15% in each of Global Deterioration scale stages 4–6 and about 5% in the most severe stage 7. Variations in age, gender, race, residence status, and education of the study sample as well as criteria used for dementia rating were found to affect prevalence.
Dementia prevalence; Centenarians; Validation
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.
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.
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.
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.
Fatigue; Oldest-old adults; Georgia Centenarian Study
Alcohol dependence is associated with neurocognitive deficits related to neuropathological changes in structure, metabolism, and function of the brain. Impairments of motor functioning in alcoholics have been attributed to well-characterized neuropathological brain abnormalities in cerebellum.
Using functional magnetic resonance imaging (fMRI), we studied in vivo the functional connectivity between cerebellar and cortical brain regions. Participants were 10 uncomplicated chronic alcoholic patients studied after 5–7 days of abstinence when signs of withdrawal had abated, and 10 matched healthy controls. We focused on regions of prefrontal, frontal, temporal, and parietal cortex that exhibited an fMRI response associated with non-dominant hand finger tapping in the patients but not in the controls. We predicted that fronto-cerebellar functional connectivity would be diminished in alcoholics compared to controls.
Functional connectivity in a circuit involving premotor areas (Brodmann Area 6) and Lobule VI of the superior cerebellum was reduced in the patients compared to the controls. Functional connectivity was also reduced in a circuit involving prefrontal cortex (Brodmann Area 9) and Lobule VIII of the inferior cerebellum. Reductions in connectivity were specific to fronto-cerebellar circuits and were not found in other regions examined.
Our findings show a pattern in recently abstinent alcoholic patients of specific deficits in functional connectivity and recruitment of additional brain regions for performance of a simple finger tapping task. A small sample, differences in smoking, and a brief abstinence period preclude definitive conclusions, but this pattern of diminished fronto-cerebellar functional connectivity is highly compatible with the characteristic neuropathological lesions documented in alcoholics, and may reflect brain dysfunction associated with alcoholism.
Alcohol; alcoholism; functional MRI; motor; connectivity
Depressive symptoms are often reported to be higher in very old populations when compared to younger age groups. However, it is unclear whether the differences are due to age differences in dysphoria or in other components of depression.
The purpose of this study was to examine age differences for specific items and subscales of the Geriatric Depression Scale (GDS).
The current study compared specific items, subscales, and the total score from the GDS among three age groups.
Community-dwelling older adults were tested.
One hundred and thirty-nine centenarians were compared to 93 octogenarians and 91 sexagenarians.
The GDS (Brink et al., 1982) was used in this study.
Results indicated age-group differences in the overall depression score and in the withdrawal-apathy-vigor (WAV), mental impairment, and hopelessness subscale scores, as well as on the item level with significant age group differences on 12 of the 30 items. Centenarians rated higher on all subscales, but there was no difference in dysphoria.
It is important to distinguish different dimensions of depression when assessing very old populations because some of the questions on the GDS are associated with fatigue, mild cognitive decline, and decline in physical functioning which increase with aging. Future research should revisit the concept of depression in very late life.
Depression; fatigue; centenarians
Prior studies have shown an increased vulnerability among males, to adverse outcomes during the postnatal period. The majority of children exposed to opioids and other medication in utero develop a neonatal abstinence syndrome (NAS), yet individual predisposition for NAS is poorly understood. This investigation examines the role of neonatal sex in the postnatal period, for neonates exposed to standardized opioid maintenance treatment in utero with a focus on the neonatal abstinence syndrome (NAS) regarding severity, medication requirements and duration.
Patients and Methods
This is a secondary analysis of data collected in a prospective randomized, double-blind, double-dummy multi-center trial examining the comparative safety and efficacy of methadone and buprenorphine during pregnancy (Maternal Opioid Treatment: Human Experimental research MOTHER – study). 131 neonates born to opioid-dependent women randomized at six US sites (n=74) and one European site (n=37) were analyzed. Sex-based differences in birth weight, length, head circumference, NAS duration, NAS severity, and treatment parameters of full-term neonates were assessed.
Males had a significantly higher birth weight (p=0.027) and head circumference (p=0.017) than females, with no significant sex difference in rates of preterm delivery. No significant sex-related differences were found for NAS development, severity, duration, or medication administered with non significant differences in concomitant drug consumption during pregnancy (p =0.959).
This unique prospective study shows similar postnatal vulnerability for both sexes, suggesting that factors other than sex are the major determinants of clinically significant NAS.
opioid dependence; methadone; buprenorphine; pregnancy; neonatal abstinence syndrome; sex differences
To investigate whether cigarette smoking and/or depression contribute to neonatal abstinence syndrome (NAS) severity.
Cohort study analyzing data from a randomized, controlled trial of methadone versus buprenorphine.
Seven study sites that randomized patients to study conditions and provided comprehensive addiction treatment to pregnant patients.
119 of 131 opioid-dependent pregnant patients who completed the MOTHER study.
Smoking data and depression status were obtained from the Addiction Severity Index and Mini International Neuropsychiatric Interview, respectively. Neonatal outcomes (birth weight, preterm delivery and NAS pharmacologic treatment) were collected from the medical charts. Study site was a fixed-effect factor in all analyses.
Cigarette smoking was reported by 94% of participants and depression identified in 35%. Smoking was associated with low birth weight, preterm delivery, and NAS pharmacologic treatment in both depressed and non-depressed participants. The association between smoking and NAS treatment differed significantly between depressed and non-depressed participants. Among non-depressed participants, adjusting for site and illicit drug use, each additional average cigarette per day (CPD) increased the odds of NAS treatment by 12% [95%CI: (1.02-1.23), p=0.02]. Among depressed participants, each additional average CPD did not statistically increase the odds of NAS treatment [OR: 0.94, 95% CI: (0.84-1.04), p=0.23].
These results are consistent with the hypothesis that NAS expression is influenced by many factors. The relationship between CPD and NAS pharmacologic treatment is attenuated among depressed women in this study for reasons currently unknown. Further investigations are needed to clarify the complex relationships among maternal smoking, depression, and NAS.
Cigarettes; depression; neonatal; pregnancy; opioids
The recalcitrance of lignocellulosic cell wall biomass to deconstruction varies greatly in angiosperms, yet the source of this variation remains unclear. Here, in eight genotypes of short rotation coppice willow (Salix sp.) variability of the reaction wood (RW) response and the impact of this variation on cell wall recalcitrance to enzymatic saccharification was considered.
A pot trial was designed to test if the ‘RW response’ varies between willow genotypes and contributes to the differences observed in cell wall recalcitrance to enzymatic saccharification in field-grown trees. Biomass composition was measured via wet chemistry and used with glucose release yields from enzymatic saccharification to determine cell wall recalcitrance. The levels of glucose release found for pot-grown control trees showed no significant correlation with glucose release from mature field-grown trees. However, when a RW phenotype was induced in pot-grown trees, glucose release was strongly correlated with that for mature field-grown trees. Field studies revealed a 5-fold increase in glucose release from a genotype grown at a site exposed to high wind speeds (a potentially high RW inducing environment) when compared with the same genotype grown at a more sheltered site.
Our findings provide evidence for a new concept concerning variation in the recalcitrance to enzymatic hydrolysis of the stem biomass of different, field-grown willow genotypes (and potentially other angiosperms). Specifically, that genotypic differences in the ability to produce a response to RW inducing conditions (a ‘RW response’) indicate that this RW response is a primary determinant of the variation observed in cell wall glucan accessibility. The identification of the importance of this RW response trait in willows, is likely to be valuable in selective breeding strategies in willow (and other angiosperm) biofuel crops and, with further work to dissect the nature of RW variation, could provide novel targets for genetic modification for improved biofuel feedstocks.
Biofuel; Willow (Salix); Lignocellulose; Reaction wood; Recalcitrance (saccharification); Cell wall Composition
Cancer cachexia is a wasting condition, driven by systemic inflammation and oxidative stress. This study investigated eicosapentaenoic acid (EPA) in combination with oxypurinol as a treatment in a mouse model of cancer cachexia. Mice with cancer cachexia were randomized into 4 treatment groups (EPA (0.4 g/kg/day), oxypurinol (1 mmol/L ad-lib), combination, or control), and euthanized after 29 days. Analysis of oxidative damage to DNA, mRNA analysis of pro-oxidant, antioxidant and proteolytic pathway components, along with enzyme activity of pro- and antioxidants were completed on gastrocnemius muscle. The control group displayed earlier onset of tumor compared to EPA and oxypurinol groups (P<0.001). The EPA group maintained body weight for an extended duration (20 days) compared to the oxypurinol (5 days) and combination (8 days) groups (P<0.05). EPA (18.2±3.2 pg/ml) and combination (18.4±3.7 pg/ml) groups had significantly higher 8-OH-dG levels than the control group (12.9±1.4 pg/ml, P≤0.05) indicating increased oxidative damage to DNA. mRNA levels of GPx1, MURF1 and MAFbx were higher following EPA treatment compared to control (P≤0.05). Whereas oxypurinol was associated with higher GPx1, MnSOD, CAT, XDH, MURF1, MAFbx and UbB mRNA compared to control (P≤0.05). Activity of total SOD was higher in the oxypurinol group (32.2±1.5 U/ml) compared to control (27.0±1.3 U/ml, P<0.01), GPx activity was lower in the EPA group (8.76±2.0 U/ml) compared to control (14.0±1.9 U/ml, P<0.05), and catalase activity was lower in the combination group (14.4±2.8 U/ml) compared to control (20.9±2.0 U/ml, P<0.01). There was no change in XO activity. The increased rate of weight decline in mice treated with oxypurinol indicates that XO may play a protective role during the progression of cancer cachexia, and its inhibition is detrimental to outcomes. In combination with EPA, there was little significant improvement from control, indicating oxypurinol is unlikely to be a viable treatment compound in cancer cachexia.
This study examined whether oldest-old adults are successful agers. Three hundred and six octogenarians and centenarians of Phase III of the Georgia Centenarian Study participated in this study. A first model examined Rowe and Kahn's successful aging model (Rowe and Khan (1997 and 1998)) including the probability of disease, physical or cognitive capacity, and engagement with life. All three components were applied to assess how many oldest-old adults satisfied all three criteria. The result showed about 15% of octogenarians (15.1%), and none of centenarians satisfied all three components of successful aging. Consequently, a second alternative model focused on psychosocial aspects including three different components: subjective health, perceived economic status, and happiness. Different from Rowe and Kahn's successful aging model, a total of 62.3% of octogenarians and 47.5% of centenarians satisfied all three components of the alternative model of successful aging. The results suggest that additional criteria of successful aging should be considered thereby expanding the concepts and multidimensional aspects of successful aging among oldest-old adults.
Objectives. Using data from the first two phases of the Georgia Centenarian Study, we proposed a latent factor structure for the Duke OARS domains: Economic Resources, Mental Health, Activities of Daily Living, Physical Health, and Social Resources. Methods. Exploratory and confirmatory factor analyses were conducted on two waves of the Georgia Centenarian Study to test a latent variable measurement model of the five resources; nested model testing was employed to assess the final measurement model for equivalency of factor structure over time. Results. The specified measurement model fit the data well at Time 1. However, at Time 2, Social Resources only had one indicator load significantly and substantively. Supplemental analyses demonstrated that a model without Social Resources adequately fit the data. Factorial invariance over time was confirmed for the remaining four latent variables. Discussion. This study's findings allow researchers and clinicians to reduce the number of OARS questions asked of participants. This has practical implications because increased difficulties with hearing, vision, and fatigue in older adults may require extended time or multiple interviewer sessions to complete the battery of OARS questions.
Purpose of the Study: There is lack of consensus on the best method of functional assessment, and there is a paucity of studies on daily functioning in centenarians. We sought to compare associations between performance-based, self-report, and proxy report of functional status in centenarians. We expected the strongest relationships between proxy reports and observed performance of basic activities of daily living (BADLs) and instrumental activities of daily living (IADLs). We hypothesized that the discrepancy between self-report and observed daily functioning would be modified by cognitive status. We additionally sought to provide clinicians with estimates of centenarians’ observed daily functioning based on their mental status in combination with subjective measures of activities of daily living (ADLs). Design and Methods: Two hundred and forty-four centenarians from the Georgia Centenarian Study were included in this cross-sectional population-based study. Measures included the Direct Assessment of Functional Status, self-report and proxy report of functional status, and the Mini-Mental State Examination (MMSE). Results: Associations between observed and proxy reports were stronger than between observed and self-report across BADL and IADL measures. A significant MMSE by type of report interaction was found, indicating that lower MMSE performance is associated with a greater discrepancy between subjective and objective ADL measures. Implications: Results demonstrate associations between 3 methods of assessing functional status and suggest proxy reports are generally more accurate than self-report measures. Cognitive status accounted for some of the discrepancy between observed and self-reports, and we provide clinicians with tables to estimate centenarians’ performance on observed functional measures based on MMSE and subjective report of functional status.
Daily functioning; Direct Assessment of Functional Status; Self-report; Proxy report; MMSE
The aim of the present study was to estimate the prevalence of unintended pregnancy and its three subtypes (mistimed, unwanted, ambivalent) among opioid-abusing women. In the general population, 31–47% of pregnancies are unintended; data on unintended pregnancy in opioid- and other drug-abusing women are lacking. Pregnant opioid-abusing women (N=946) screened for possible enrollment in a multi-site randomized controlled trial comparing opioid maintenance medications completed a standardized interview assessing sociodemographic characteristics, current and past drug use, and pregnancy intention. Almost 9 of every 10 pregnancies were unintended (86%), with comparable percentages mistimed (34%), unwanted (27%), and ambivalent (26%). Irrespective of pregnancy intention, more than 90% of the total sample had a history of drug abuse treatment, averaging more than 3 treatment episodes. Interventions are sorely needed to address the extremely high rate of unintended pregnancy among opioid-abusing women. Drug treatment programs are likely to be an important setting for such interventions.
Pregnancy; intention; family planning; opioid; drug abuse
Gamma-aminobutyric acid (GABA) and glutamate (Glu) levels, normalized to total creatine (tCr) were measured in the anterior cingulate and cerebellar vermis in healthy adults (n=19, age = 24.6 +/ 6.4 yrs) using 1H MRS at 3 Tesla and metabolite correlations across regions and subjects were determined. Mean anterior cingulate and cerebellar GABA:tCr ratios were 0.31 (0.08) and 0.23 (0.06), respectively, while corresponding Glu levels were 1.16 (0.10) and 0.70 (0.07), respectively. A correlation was observed for glutamate (r = 0.61, p = 0.01 and p = 0.06 when adjusted for multiple comparisons) between the anterior cingulate and the cerebellar vermis. It is unlikely that this correlation is driven by correlations in tCr, since inter-regional correlations were not observed for other metabolites referenced to tCr. Within both regions, correlations were observed between metabolites which were also weakly significant when correcting for multiple comparisons. N-acetyl-aspartate and glutamate (anterior cingulate: r = 0.66, p = 0.01 and p = 0.06 when adjusted for multiple comparisons; cerebellar vermis: r = 0.64, p = 0.01 and p = 0.06 when adjusted for multiple comparisons).
gamma-aminobutyric acid; GABA; glutamate; anterior cingulate; cerebellar vermis; J-Difference; MRS; metabolite correlations
This study examined change over time in five resources assessed by the Duke OARS Multidisciplinary Functional Assessment Questionnaire: social, economic, mental, physical, and functional resources. Two hundred and one participants in the Georgia Centenarian Study provided data for this longitudinal study: 70 sexagenarians, 63 octogenarians, and 68 centenarians. Those in their 60s and 80s were followed up within 60 months; due to mortality attrition, centenarians were followed up within 20 months. Centenarians experienced the lowest levels of resources relative to those in their 80s and 60s. Over time they primarily experienced loss in activities of daily living, highlighting that the ability to maximize gains and mitigate losses over time for older adults is highly associated with various resources essential to well-being. Findings suggest that older adults'—especially the very old—resources should be concurrently assessed in a multidimensional analysis by researchers and practitioners who work with older adults in various settings.
This study provides, for the first time, normative data on cognitive functioning and physical performance, health and health behaviors, and diseases from a population-based sample of 244 centenarians and near-centenarians (M age = 100.5 years, range 98-108, 84.8% women, 21.3% African American) from the Georgia Centenarian Study. Data are presented by the four key dimensions of gender, race, residence, and educational attainment. Results illustrate the profound range of functioning in this age group and indicate considerable differences as a function of each dimension. Bivariate models generally suggest that cognitive functioning and physical performance is higher for: men than women; whites than African Americans; community than facility residents; those with more than high school education than those with less than high school education. Multivariate models elaborate that differences in educational attainment generally account for the largest proportion of variance in cognitive functioning and residential status generally accounts for the largest proportion of variance in physical performance measures. Addition of health variables seldom increases variance accounted for in each domain beyond these four dimensions.
The interaction of psychiatric symptoms with drug dependence during pregnancy is not well understood. This study examines the relationship of psychiatric symptoms to severity of drug use and drug related problems among participants in a clinical trial of pharmacologic treatment of opioid dependence during pregnancy (N=174). 64.6% reported additional psychiatric symptoms (48.6% mood symptoms, 40.0% anxiety symptoms, and 12.6% suicidal thinking). Women who endorsed co-occurring psychiatric symptoms showed more severe impairment on the Addiction Severity Index (ASI). Further investigation is warranted to understand the effect of psychiatric symptoms on long-term maternal and neonatal outcomes.
The aim of this investigation was to determine how cognitive performance was associated with positive and negative affect and life satisfaction over time. This study involved a secondary longitudinal analysis of cross-section data collected at Phase I (1988–1992) and during an 18-month longitudinal followup at Phase II (1992–1998) of the Georgia Centenarian Study. Participants included N = 137 centenarians at Time 1 and N = 68 survivors at Time 2. Significant stability in cognitive impairment existed at Time 1 and Time 2 for positive (β = .55, P < .01) and negative affect (β = .54, P < .01) models. Negative affect at Time 1 was associated with lower life satisfaction at Time 1 (β = −.42, P < .01
). In addition, cognitive impairment at Time 2 was associated with decreased positive emotionality at Time 2 (β = −.39, P > .01). Furthermore, greater positive affect at Time 2 was associated with greater satisfaction with life at Time 2 (β = .35, P < .01). It appears that positive emotionality contemporaneously influences the association between cognitive impairment and life satisfaction among centenarians. Implications relative to improving life satisfaction among centenarians are discussed.