Delayed senescence and crop performance under stress: always a functional couple?

Exposure to abiotic stresses accelerates leaf senescence in most crop plant species, thereby reducing photosynthesis and other assimilatory processes. In some cases, genotypes with delayed leaf senescence (i.e., "stay-greens") show stress resistance, particularly in cases of water deficit, and this has led to the proposal that senescence delay improves crop performance under some abiotic stresses. In this review, we summarize the evidence for increased resistance to abiotic stress, mostly water deficit, in genotypes with delayed senescence, and specifically focus on the physiological mechanisms and agronomic conditions under which the stay-green trait may ameliorate grain yield under stress.

Do photosynthetic cells communicate with each other during cell death? From cyanobacteria to vascular plants.

As in metazoans, life in oxygenic photosynthetic organisms relies on the accurate regulation of cell death. During development and in response to the environment, photosynthetic cells activate and execute cell death pathways that culminate in the death of a specific group of cells, a process known as regulated cell death (RCD). RCD control is instrumental, as its misregulation can lead to growth penalties and even the death of the entire organism. Intracellular molecules released during cell demise may act as 'survival' or 'death' signals and control the propagation of cell death to surrounding cells, even in unicellular organisms. This review explores different signals involved in cell-cell communication and systemic signalling in photosynthetic organisms, in particular Ca2+, reactive oxygen species, lipid derivates, nitric oxide, and eATP. We discuss their possible mode-of-action as either 'survival' or 'death' molecules and their potential role in determining cell fate in neighbouring cells. By comparing the knowledge available across the taxonomic spectrum of this coherent phylogenetic group, from cyanobacteria to vascular plants, we aim at contributing to the identification of conserved mechanisms that control cell death propagation in oxygenic photosynthetic organisms.

Chloroplast Protein Degradation in Senescing Leaves: Proteases and Lytic Compartments.

Leaf senescence is characterized by massive degradation of chloroplast proteins, yet the protease(s) involved is(are) not completely known. Increased expression and/or activities of serine, cysteine, aspartic, and metalloproteases were detected in senescing leaves, but these studies have not provided information on the identities of the proteases responsible for chloroplast protein breakdown. Silencing some senescence-associated proteases has delayed progression of senescence symptoms, yet it is still unclear if these proteases are directly involved in chloroplast protein breakdown. At least four cellular pathways involved in the traffic of chloroplast proteins for degradation outside the chloroplast have been described (i.e., "Rubisco-containing bodies," "senescence-associated vacuoles," "ATI1-plastid associated bodies," and "CV-containing vesicles"), which differ in their dependence on the autophagic machinery, and the identity of the proteins transported and/or degraded. Finding out the proteases involved in, for example, the degradation of Rubisco, may require piling up mutations in several senescence-associated proteases. Alternatively, targeting a proteinaceous protein inhibitor to chloroplasts may allow the inhibitor to reach "Rubisco-containing bodies," "senescence-associated vacuoles," "ATI1-plastid associated bodies," and "CV-containing vesicles" in essentially the way as chloroplast-targeted fluorescent proteins re-localize to these vesicular structures. This might help to reduce proteolytic activity, thereby reducing or slowing down plastid protein degradation during senescence.

Social stratification and allostatic load: shapes of health differences in the MIDUS study in the United States.

Social stratification is an important mechanism of human organization that helps to explain health differences between demographic groups commonly associated with socioeconomic gradients. Individuals, or group of individuals, with similar health profiles may have had different stratification experiences. This is particularly true as social stratification is a significant non-measurable source of systematic unobservable differences in both SES indicators and health statuses of disadvantage. The goal of the present study was to expand the bulk of research that has traditionally treated socioeconomic and demographic characteristics as independent, additive influences on health by examining data from the United States. It is hypothesized that variation in an index of multi-system physiological dysregulation - allostatic load - is associated with social differentiation factors, sorting individuals with similar demographic and socioeconomic characteristics into mutually exclusive econo-demographic classes. The data were from the Longitudinal and Biomarker samples of the national Study of Midlife Development in the US (MIDUS) conducted in 1995 and 2004/2006. Latent class analyses and regression analyses revealed that physiological dysregulation linked to socioeconomic variation among black people, females and older adults are associated with forces of stratification that confound socioeconomic and demographic indicators. In the United States, racial stratification of health is intrinsically related to the degree to which black people in general, and black females in particular, as a group, share an isolated status in society. Findings present evidence that disparities in health emerge from group-differentiation processes to the degree that individuals are distinctly exposed to the ecological, political, social, economic and historical contexts in which social stratification is ingrained. Given that health policies and programmes emanate from said legal and political environments, interventions should target the structural conditions that expose different subgroups to different stress risks in the first place.

Physiological and Proteomic Changes in the Apoplast Accompany Leaf Senescence in Arabidopsis.

The apoplast, i.e. the cellular compartment external to the plasma membrane, undergoes important changes during senescence. Apoplastic fluid volume increases quite significantly in senescing leaves, thereby diluting its contents. Its pH elevates by about 0.8 units, similar to the apoplast alkalization in response to abiotic stresses. The levels of 159 proteins decrease, whereas 24 proteins increase in relative abundance in the apoplast of senescing leaves. Around half of the apoplastic proteins of non-senescent leaves contain a N-terminal signal peptide for secretion, while all the identified senescence-associated apoplastic proteins contain the signal peptide. Several of the apoplastic proteins that accumulate during senescence also accumulate in stress responses, suggesting that the apoplast may constitute a compartment where developmental and stress-related programs overlap. Other senescence-related apoplastic proteins are involved in cell wall modifications, proteolysis, carbohydrate, ROS and amino acid metabolism, signaling, lipid transport, etc. The most abundant senescence-associated apoplastic proteins, PR2 and PR5 (e.g. pathogenesis related proteins PR2 and PR5) are related to leaf aging rather than to the chloroplast degradation program, as their levels increase only in leaves undergoing developmental senescence, but not in dark-induced senescent leaves. Changes in the apoplastic space may be relevant for signaling and molecular trafficking underlying senescence.

3D electron tomographic and biochemical analysis of ER, Golgi and trans Golgi network membrane systems in stimulated Venus flytrap (Dionaea muscipula) glandular cells.

BACKGROUND: The insect-trapping leaves of Dionaea muscipula provide a model for studying the secretory pathway of an inducible plant secretory system. The leaf glands were induced with bovine serum albumin to secrete proteases that were characterized via zymogram activity gels over a 6-day period. The accompanying morphological changes of the endoplasmic reticulum (ER) and Golgi were analyzed using 3D electron tomography of glands preserved by high-pressure freezing/freeze substitution methods. RESULTS: Secretion of multiple cysteine and aspartic proteases occurred biphasically. The majority of the Golgi was organized in clusters consisting of 3-6 stacks surrounded by a cage-like system of ER cisternae. In these clusters, all Golgi stacks were oriented with their cis-most C1 cisterna facing an ER export site. The C1 Golgi cisternae varied in size and shape consistent with the hypothesis that they form de novo. Following induction, the number of ER-bound polysomes doubled, but no increase in COPII vesicles was observed. Golgi changes included a reduction in the number of cisternae per stack and a doubling of cisternal volume without increased surface area. Polysaccharide molecules that form the sticky slime cause swelling of the trans and trans Golgi network (TGN) cisternae. Peeling of the trans-most cisternae gives rise to free TGN cisternae. One day after gland stimulation, the free TGNs were frequently associated with loose groups of oriented actin-like filaments which were not seen in any other samples. CONCLUSIONS: These findings suggest that the secretory apparatus of resting gland cells is "overbuilt" to enable the cells to rapidly up-regulate lytic enzyme production and secretion in response to prey trapping.

Activities of Vacuolar Cysteine Proteases in Plant Senescence.

Plant senescence is accompanied by a marked increase in proteolytic activities, and cysteine proteases (Cys-protease) represent the prevailing class among the responsible proteases. Cys-proteases predominantly locate to lytic compartments, i.e., to the central vacuole (CV) and to senescence-associated vacuoles (SAVs), the latter being specific to the photosynthetic cells of senescing leaves. Cellular fractionation of vacuolar compartments may facilitate Cys-proteases purification and their concentration for further analysis. Active Cys-proteases may be analyzed by different, albeit complementary approaches: (1) in vivo examination of proteolytic activity by fluorescence microscopy using specific substrates which become fluorescent upon cleavage by Cys-proteases, (2) protease labeling with specific probes that react irreversibly with the active enzymes, and (3) zymography, whereby protease activities are detected in polyacrylamide gels copolymerized with a substrate for proteases. Here we describe the three methods mentioned above for detection of active Cys-proteases and a cellular fractionation technique to isolate SAVs.

From structure to function - a family portrait of plant subtilases.

Contents Summary 901 I. Introduction 901 II. Biochemistry and structure of plant SBTs 902 III. Phylogeny of plant SBTs and family organization 903 IV. Physiological roles of plant SBTs 905 V. Conclusions and outlook 911 Acknowledgements 912 References 912 SUMMARY: Subtilases (SBTs) are serine peptidases that are found in all three domains of life. As compared with homologs in other Eucarya, plant SBTs are more closely related to archaeal and bacterial SBTs, with which they share many biochemical and structural features. However, in the course of evolution, functional diversification led to the acquisition of novel, plant-specific functions, resulting in the present-day complexity of the plant SBT family. SBTs are much more numerous in plants than in any other organism, and include enzymes involved in general proteolysis as well as highly specific processing proteases. Most SBTs are targeted to the cell wall, where they contribute to the control of growth and development by regulating the properties of the cell wall and the activity of extracellular signaling molecules. Plant SBTs affect all stages of the life cycle as they contribute to embryogenesis, seed development and germination, cuticle formation and epidermal patterning, vascular development, programmed cell death, organ abscission, senescence, and plant responses to their biotic and abiotic environments. In this article we provide a comprehensive picture of SBT structure and function in plants.

Bevacizumab for the treatment of a complicated posterior melanocytoma.

PURPOSE: To present a case of a complicated posterior melanocytoma that was successfully treated with intravitreal bevacizumab. CASE REPORT: A 50-year-old Caucasian man was referred with sudden-onset metamorphopsia and decreased vision in his right eye over the course of the last 2 months. His best-corrected visual acuity was 20/80 and poorer than Jaeger 14 in the right eye, and 20/20 and Jaeger 1 in his left eye. In the right fundus, there was a melanocytic lesion occupying the inferotemporal quadrant of the optic disk, extending to the adjacent choroid inferiorly; optic nerve edema, superotemporal retinal vein dilatation, and subretinal fluid under the macula and nasal half of the posterior pole were observed, and a subretinal choroidal neovascularization complex was observed adjacent to the superotemporal margin of the optic disk, confirmed by fluorescein angiography, surrounded by a dense subretinal hemorrhage. Optical coherence tomography showed retinal edema and detachment of neurosensory retina. The patient was treated with three consecutive doses on a monthly basis of intravitreal 1.25 mg/0.05 mL bevacizumab. Visual acuity recovered rapidly, and at 4 months after treatment, it was 20/20 and Jaeger 1, with complete resolution of macular edema and subretinal fluid and hemorrhage. After 3 years of follow-up, best-corrected visual acuity remained stable, macular area was normal, and there was no evident optic nerve edema, retinal vein caliber and aspect were normal, and there was no significant change of the tumor. Fluorescein angiography only evidenced late staining of choroidal neovascularization scar, and optical coherence tomography showed a normal macular anatomy. CONCLUSION: Intravitreal bevacizumab was effective in the treatment of choroidal neovascularization, optic nerve edema, venous dilatation, and local capillary telangiectasia, complicating an optic disk melanocytoma.

SASP, a Senescence-Associated Subtilisin Protease, is involved in reproductive development and determination of silique number in Arabidopsis.

Senescence involves increased expression of proteases, which may participate in nitrogen recycling or cellular signalling. 2D zymograms detected two protein species with increased proteolytic activity in senescing leaves of Arabidopsis thaliana. A proteomic analysis revealed that both protein species correspond to a subtilisin protease encoded by At3g14067, termed Senescence-Associated Subtilisin Protease (SASP). SASP mRNA levels and enzyme activity increase during leaf senescence in leaves senescing during both the vegetative or the reproductive phase of the plant life cycle, but this increase is more pronounced in reproductive plants. SASP is expressed in all above-ground organs, but not in roots. Putative AtSASP orthologues were identified in dicot and monocot crop species. A phylogenetic analysis shows AtSASP and its putative orthologues clustering in one discrete group of subtilisin proteases in which no other Arabidospsis subtilisin protease is present. Phenotypic analysis of two knockout lines for SASP showed that mutant plants develop more inflorescence branches during reproductive development. Both AtSASP and its putative rice orthologue (OsSASP) were constitutively expressed in sasp-1 to complement the mutant phenotype. At maturity, sasp-1 plants produced 25% more inflorescence branches and siliques than either the wild-type or the rescued lines. These differences were mostly due to an increased number of second and third order branches. The increased number of siliques was compensated for by a small decrease (5.0%) in seed size. SASP downregulates branching and silique production during monocarpic senescence, and its function is at least partially conserved between Arabidopsis and rice.

Preparing the workforce for healthy aging programs: the Skills for Healthy Aging Resources and Programs (SHARP) model.

Current public health and aging service agency personnel have little training in gerontology, and virtually no training in evidence-based health promotion and disease management programs for older adults. These programs are rapidly becoming the future of our community-based long-term care support system. The purpose of this project was to develop and test a model community college career technical education program, Skills for Healthy Aging Resources and Programs (SHARP), for undergraduate college students, current personnel in aging service and community organizations, and others interested in retraining. A multidisciplinary cross-sector team from disciplines of public health, sociology, gerontology and nursing developed four competency-based courses that focus on healthy aging, behavior change strategies, program management, an internship, and an option for leader training in the Chronic Disease Self-Management Program. To enhance implementation and fidelity, intensive faculty development training was provided to all instructors and community agency partners. Baseline and postprogram evaluation of competencies for faculty and students was conducted. Process evaluation for both groups focused on satisfaction with the curricula and suggestions for program improvement. SHARP has been piloted five times at two community colleges. Trainees (n = 113) were primarily community college students (n = 108) and current aging service personnel (n = 5). Statistically significant improvements in all competencies were found for both faculty and students. Process evaluation outcomes identified the needed logical and component adaptations to enhance the feasibility of program implementation, dissemination, and student satisfaction. The SHARP program provides a well-tested, evidence-based effective model for addressing workforce preparation in support of healthy aging service program expansion and delivery.

Hyperkyphosis, kyphosis progression, and risk of non-spine fractures in older community dwelling women: the study of osteoporotic fractures (SOF).

While accentuated kyphosis is associated with osteoporosis, it is unknown whether it increases risk of future fractures, independent of bone mineral density (BMD) and vertebral fractures. We examined the associations of baseline Cobb angle kyphosis and 15 year change in kyphosis with incident non-spine fractures using data from the Study of Osteoporotic Fractures. A total of 994 predominantly white women, aged 65 or older, were randomly sampled from 9704 original participants to have repeated Cobb angle measurements of kyphosis measured from lateral spine radiographs at baseline and an average of 15 years later. Non-spine fractures, confirmed by radiographic report, were assessed every 4 months for up to 21.3 years. Compared with women in the lower three quartiles of kyphosis, women with kyphosis greater than 53° (top quartile) had a 50% increased risk of non-spine fracture (95% CI, 1.10-2.06 after adjusting for BMD, prevalent vertebral fractures, prior history of fractures, and other fracture risk factors. Cobb angle kyphosis progressed an average of 7° (SD = 6.8) over 15 years. Per 1 SD increase in kyphosis change, there was a multivariable adjusted 28% increased risk of fracture (95% CI, 1.06-1.55) that was attenuated by further adjustment for baseline BMD (HR per SD increase in kyphosis change, 1.19; 95% CI 0.99-1.44). Greater kyphosis is associated with an elevated non-spine fracture risk independent of traditional fracture risk factors in older women. Furthermore, worsening kyphosis is also associated with increased fracture risk that is partially mediated by low baseline BMD that itself is a risk factor for kyphosis progression. These results suggest that randomized controlled fracture intervention trials should consider implementing kyphosis measures to the following: (1) further study kyphosis and kyphosis change as an additional fracture risk factor; and (2) test whether therapies may improve or delay its progression.

Kyphosis and paraspinal muscle composition in older men: a cross-sectional study for the Osteoporotic Fractures in Men (MrOS) research group.

BACKGROUND: The prevalence of hyperkyphosis is increased in older men; however, risk factors other than age and vertebral fractures are not well established. We previously reported that poor paraspinal muscle composition contributes to more severe kyphosis in a cohort of both older men and women. METHODS: To specifically evaluate this association in older men, we conducted a cross-sectional study to evaluate the association of paraspinal muscle composition and degree of thoracic kyphosis in an analytic cohort of 475 randomly selected participants from the Osteoporotic Fractures in Men (MrOS) study with baseline abdominal quantitative computed tomography (QCT) scans and plain thoracic radiographs. Baseline abdominal QCT scans were used to obtain abdominal body composition measurements of paraspinal muscle and adipose tissue distribution. Supine lateral spine radiographs were used to measure Cobb angle of kyphosis. We examined the linear association of muscle volume, fat volume and kyphosis using loess plots. Multivariate linear models were used to investigate the association between muscle and kyphosis using total muscle volume, as well as individual components of the total muscle volume, including adipose and muscle compartments alone, controlling for age, height, vertebral fractures, and total hip bone mineral density (BMD). We examined these associations among those with no prevalent vertebral fracture and those with BMI < 30 kg/m2. RESULTS: Among men in the analytic cohort, means (SD) were 74 (SD = 5.9) years for age, and 37.5 (SD = 11.9) degrees for Cobb angle of kyphosis. Men in the lowest tertile of total paraspinal muscle volume had greater mean Cobb angle than men in the highest tertile, although test of linear trend across tertiles did not reach statistical significance. Neither lower paraspinal skeletal muscle volume (p-trend = 0.08), or IMAT (p-trend = 0.96) was associated with greater kyphosis. Results were similar among those with no prevalent vertebral fractures. However, among men with BMI < 30 kg/m2, those in the lowest tertile of paraspinal muscle volume had greater adjusted mean kyphosis (40.0, 95% CI: 37.8 - 42.1) compared to the highest tertile (36.3, 95% CI: 34.2 - 38.4). CONCLUSIONS: These results suggest that differences in body composition may potentially influence kyphosis.

Insulin resistance and bone strength: findings from the study of midlife in the United States.

Although several studies have noted increased fracture risk in individuals with type 2 diabetes mellitus (T2DM), the pathophysiologic mechanisms underlying this association are not known. We hypothesize that insulin resistance (the key pathology in T2DM) negatively influences bone remodeling and leads to reduced bone strength. Data for this study came from 717 participants in the Biomarker Project of the Midlife in the United States Study (MIDUS II). The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated from fasting morning blood glucose and insulin levels. Projected 2D (areal) bone mineral density (BMD) was measured in the lumbar spine and left hip using dual-energy X-ray absorptiometry (DXA). Femoral neck axis length and width were measured from the hip DXA scans, and combined with BMD and body weight and height to create composite indices of femoral neck strength relative to load in three different failure modes: compression, bending, and impact. We used multiple linear regressions to examine the relationship between HOMA-IR and bone strength, adjusted for age, gender, race/ethnicity, menopausal transition stage (in women), and study site. Greater HOMA-IR was associated with lower values of all three composite indices of femoral neck strength relative to load, but was not associated with BMD in the femoral neck. Every doubling of HOMA-IR was associated with a 0.34 to 0.40 SD decrement in the strength indices (p<0.001). On their own, higher levels of fasting insulin (but not of glucose) were independently associated with lower bone strength. Our study confirms that greater insulin resistance is related to lower femoral neck strength relative to load. Further, we note that hyperinsulinemia, rather than hyperglycemia, underlies this relationship. Although cross-sectional associations do not prove causality, our findings do suggest that insulin resistance and in particular, hyperinsulinemia, may negatively affect bone strength relative to load.

Biological correlates of adult cognition: midlife in the United States (MIDUS).

Multiple biological processes are related to cognitive impairment in older adults, but their combined impact on cognition in midlife is not known. Using an array of measurements across key regulatory physiological systems and a state-of-the-art cognition battery that is sensitive to early changes, in a large, national sample of middle-aged and older adults, we examined the associations of individual biological systems and a combined, multi-system index, allostatic load, with cognitive performance. Allostatic load was strongly inversely associated with performance in both episodic memory and executive function. Of 7 biological systems, only the cardiovascular system was associated inversely with both; inflammation was associated inversely with episodic memory only, and glucose metabolism with executive function only. The associations of allostatic load with cognition were not different by age, suggesting that the implications of high allostatic load on cognitive functioning are not restricted to older adults. Findings suggest that a multi-system score, like allostatic load, may assist in the early identification of adults at increased risk for cognitive impairment.

Senescence-Associated Vacuoles, a Specific Lytic Compartment for Degradation of Chloroplast Proteins?

Degradation of chloroplasts and chloroplast components is a distinctive feature of leaf senescence. In spite of its importance in the nutrient economy of plants, knowledge about the mechanism(s) involved in the breakdown of chloroplast proteins is incomplete. A novel class of vacuoles, "senescence-associated vacuoles" (SAVs), characterized by intense proteolytic activity appear during senescence in chloroplast-containing cells of leaves. Since SAVs contain some chloroplast proteins, they are candidate organelles to participate in chloroplast breakdown. In this review we discuss the characteristics of SAVs, and their possible involvement in the degradation of Rubisco, the most abundant chloroplast protein. Finally, SAVs are compared with other extra-plastidial protein degradation pathways operating in senescing leaves.

In vivo inhibition of cysteine proteases provides evidence for the involvement of 'senescence-associated vacuoles' in chloroplast protein degradation during dark-induced senescence of tobacco leaves.

Breakdown of leaf proteins, particularly chloroplast proteins, is a massive process in senescing leaves. In spite of its importance in internal N recycling, the mechanism(s) and the enzymes involved are largely unknown. Senescence-associated vacuoles (SAVs) are small, acidic vacuoles with high cysteine peptidase activity. Chloroplast-targeted proteins re-localize to SAVs during senescence, suggesting that SAVs might be involved in chloroplast protein degradation. SAVs were undetectable in mature, non-senescent tobacco leaves. Their abundance, visualized either with the acidotropic marker Lysotracker Red or by green fluorescent protein (GFP) fluorescence in a line expressing the senescence-associated cysteine protease SAG12 fused to GFP, increased during senescence induction in darkness, and peaked after 2-4 d, when chloroplast dismantling was most intense. Increased abundance of SAVs correlated with higher levels of SAG12 mRNA. Activity labelling with a biotinylated derivative of the cysteine protease inhibitor E-64 was used to detect active cysteine proteases. The two apparently most abundant cysteine proteases of senescing leaves, of 40kDa and 33kDa were detected in isolated SAVs. Rubisco degradation in isolated SAVs was completely blocked by E-64. Treatment of leaf disks with E-64 in vivo substantially reduced degradation of Rubisco and leaf proteins. Overall, these results indicate that SAVs contain most of the cysteine protease activity of senescing cells, and that SAV cysteine proteases are at least partly responsible for the degradation of stromal proteins of the chloroplast.

Social strain and executive function across the lifespan: the dark (and light) sides of social engagement.

We investigated how the association between social strain and cognitive efficiency varies with task demands across adulthood, from latencies on simpler speeded tasks to tests involving executive function. Participants (N = 3280) were drawn from the MIDUS survey, a large, diverse national sample of adults who completed cognitive tests including speeded task-switching (Tun & Lachman, 2008, Developmental Psychology, 44, 1421). After controlling for demographic and health variables, we found that higher levels of reported social strain were associated with slower processing speed, particularly for the complex task-switching test relative to simpler speeded tests. Effects of strain were greatest for those with the lowest general cognitive ability. Moreover, those with very high levels of social strain but low levels of social support gave the poorest task-switching performance. These findings provide further evidence for the complex relationship between the social environment and cognition across adulthood, particularly the association between efficiency of executive functions and negative social interactions.

Histories of social engagement and adult cognition: midlife in the U.S. study.

OBJECTIVES: To evaluate whether social contacts, support, and social strain/conflict are related to executive function and memory abilities in middle-age and older adults. METHODS: Longitudinal data on social contacts, support, and strain/conflict were examined in relation to executive function and memory at ages 35-85 years using data from the national Midlife in the U.S. (MIDUS) study. Age-related differences in patterns of association were also examined. RESULTS: Regression analyses, controlling for age, sex, race, education, chronic health conditions, and health behaviors, revealed significant positive associations between histories of greater social contacts and support and both executive function and episodic memory, whereas declines in social contacts were negatively associated with both outcomes. Greater average reported frequency of social exchanges characterized by strain or conflict was negatively associated with executive function but not episodic memory. Patterns were generally consistent across different age groups; where differences were seen, associations were stronger in younger age group. DISCUSSION: Positive and negative aspects of social relationships are related to cognition throughout adulthood, consistent with the hypothesis that social factors have life-long influences on cognition. Positive and negative aspects of social engagement may thus be important factors to consider in relation to efforts to promote optimal cognitive development and cognitive aging.

Depressive symptoms, chronic diseases, and physical disabilities as predictors of cognitive functioning trajectories in older Americans.

OBJECTIVES: To determine the concurrent influence of depressive symptoms, medical conditions, and disabilities in activities of daily living (ADLs) on rates of decline in cognitive function of older Americans. DESIGN: Prospective cohort. SETTING: National population based. PARTICIPANTS: A national sample of 6,476 adults born before 1924. MEASUREMENTS: Differences in cognitive function trajectories were determined according to prevalence and incidence of depressive symptoms, chronic diseases, and ADL disabilities. Cognitive performance was tested five times between 1993 and 2002 using a multifaceted inventory examined as a global measure (range 0-35, standard deviation (SD) 6.0) and word recall (range 0-20, SD 3.8) analyzed separately. RESULTS: Baseline prevalence of depressive symptoms, stroke, and ADL limitations were independently and strongly associated with lower baseline cognition scores but did not predict future cognitive decline. Each incident depressive symptom was independently associated with a 0.06-point lower (95% confidence interval (CI)=0.02-0.10) recall score, incident stroke with a 0.59-point lower total score (95% CI=0.20-0.98), each new basic ADL limitation with a 0.07-point lower recall score (95% CI=0.01-0.14) and a 0.16-point lower total score (95% CI=0.07-0.25), and each incident instrumental ADL limitation with a 0.20-point lower recall score (95% CI=0.10-0.30) and a 0.52-point lower total score (95% CI=0.37-0.67). CONCLUSION: Prevalent and incident depressive symptoms, stroke, and ADL disabilities contribute independently to poorer cognitive functioning in older Americans but do not appear to influence rates of future cognitive decline. Prevention, early identification, and aggressive treatment of these conditions may ameliorate the burdens of cognitive impairment.