Development of a new multidimensional individual and interpersonal resilience measure for older adults

Objectives: Develop an empirically grounded measure that can be used to assess family and individual resilience in a population of older adults (aged 50–99).

Methods: Cross-sectional, self-report data from 1006 older adults were analyzed in two steps. The total sample was split into two subsamples and the first step identified the underlying latent structure through principal component exploratory factor analysis (EFA). The second step utilized the second half of the sample to validate the derived latent structure through confirmatory factor analysis (CFA).

Results: EFA produced an eight-factor structure that appeared clinically relevant for measuring the multidimensional nature of resilience. Factors included self-efficacy, access to social support network, optimism, perceived economic and social resources, spirituality and religiosity, relational accord, emotional expression and communication, and emotional regulation. CFA confirmed the eight-factor structure previously achieved with covariance between each of the factors. Based on these analyses we developed the multidimensional individual and interpersonal resilience measure, a broad assessment of resilience for older adults.

Conclusion: This study highlights the multidimensional nature of resilience and introduces an individual and interpersonal resilience measure developed for older adults which is grounded in the individual and family resilience literature.     

Relationships among depressive,passive-aggressive,sadistic and self-defeating personality disorder features with suicidal ideation and reasons for living among older adults

Objectives: Suicide among older adults is a major public health problem in the USA. In our recent study, we examined relationships between the 10 standard DSM-5 personality disorders (PDs) and suicidal ideation, and found that the PD dimensions explained a majority (55%) of the variance in suicidal ideation. To extend this line of research, the purpose of the present follow-up study was to explore relationships between the four PDs that previously were included in prior versions of the DSM (depressive, passive-aggressive, sadistic, and self-defeating) with suicidal ideation and reasons for living.

Method: Community-dwelling older adults (N = 109; age range = 60–95 years; 61% women; 88% European-American) completed anonymously the Coolidge Axis II Inventory, the Reasons for Living Inventory (RFL), and the Geriatric Suicide Ideation Scale (GSIS).

Results: Correlational analyses revealed that simple relationships between PD scales with GSIS subscales were generally stronger than with RFL subscales. Regarding GSIS subscales, all four PD scales had medium-to-large positive relationships, with the exception of sadistic PD traits, which was unrelated to the death ideation subscale. Multiple regression analyses showed that the amount of explained variance for the GSIS (48%) was higher than for the RFL (11%), and this finding was attributable to the high predictive power of depressive PD.

Conclusion: These findings suggest that depressive PD features are strongly related to increased suicidal thinking and lowered resilience to suicide among older adults. Assessment of depressive PD features should also be especially included in the assessment of later-life suicidal risk.     

Stress on health-related quality of life in older adults: the protective nature of mindfulness

Objectives: The current study examined whether the link between stress and health-related quality of life was buffered by protective factors, namely mindfulness, in a sample of middle-aged and older adults.

Methods: In this cross-sectional study, 134 healthy, community-dwelling adults (ages 50–85 years) were recruited from Dallas, TX. The participants were screened for depressive symptoms and severity (using the Patient Health Questionnaire [PHQ-9]). All participants completed measures of self-reported health status (i.e. SF36v2: mental and physical health composites), life stress (using the Elders Life Stress Inventory [ELSI]), and trait mindfulness (i.e. Mindful Attention Awareness Scale).

Results: Hierarchical regressions (covarying for age, gender, and education) showed that life stress was inversely related to physical and mental health. Mindfulness was positively related to mental health. The negative effect of life stress on mental health was weakened for those individuals with higher levels of trait mindfulness.

Conclusions: The results suggest that mindfulness is a powerful, adaptive strategy that may protect middle-aged and older adults from the well-known harmful effects of stress on mental health.     

Age-related changes in duodenal adaptation after distal small bowel resection in rat

Two groups of male Fisher 344 rats (young: 4 months old; aged: 25 months old) underwent either 70% distal small bowel resection or sham operation (small bowel transection). Rats from each treatment group of each age were sacrificed on the 10th (N=15: young rats;N=13: aged rats) or 20th (N=15: young;N=13: aged) postoperative day (POD), and the duodenal mucosa was weighed and assayed for DNA, RNA, and protein contents, as well as for specific activities of the disaccharidase, sucrase, maltase, and lactase. Compared to the sham operation, distal small bowel resection significantly increased DNA by 48%, RNA by 122%, and protein by 75% in young rats and DNA by 40%, RNA by 92%, and protein by 71% in aged rats on the 20th POD. Both young and aged rats showed similar adaptive hyperplasia on the 10th POD. On the 20th POD after distal small bowel resection, specific activities of all tested enzymes were significantly increased in young rats (sucrase +86%, maltase +110% and lactase +64%), but showed no significant changes in aged rats. These findings suggest that the duodenum of aged rats may have sufficient proliferative potential to respond to distal small bowel resection, but that the mechanisms governing return of function in response to distal small bowel resection are inhibited in aged rats, compared to those mechanisms in the young.Supported by grants from the National Institutes of Health (5R37 DK15241, P01 DK 35608).     

Anti-mullerian hormone (AMH) is associated with natural menopause in a population-based sample: The CARDIA Women's Study

ObjectiveAMH is associated with menopausal timing in several studies. In contrast to prior studies that were restricted to women with regular cycles, our objective was to examine this association in women with either regular or irregular menstrual cycles.MethodsCARDIA is a longitudinal, population-based study that recruited adults ages 18–30 when it began in 1985–1986. AMH was measured in serum stored in 2002–2003. Natural menopause was assessed by survey in 2005–2006 and 2010–2011.ResultsAmong 716 premenopausal women, median [25th, 75th] AMH was 0.77 [0.22–2.02] ng/dL at a median age of 42 [39–45] years. Twenty-nine percent of the women (n = 207) reported natural menopause during 9 years of follow up. In fully adjusted discrete-time hazard models, a 0.5 ng/dL AMH decrement was associated with higher risk of menopause (p < 0.001). Hazard ratios varied with time since AMH measurement. The HR (95% CI) for menopause was 8.1 (2.5–26.1) within 0–3 years and 2.3 (1.7–3.3) and 1.6 (1.3–2.1) for 3–6 and 6–9 years, respectively. When restricted to women with regular menses, results were similar (e.g., HR = 6.1; 95% CI: 1.9–20.0 for 0–3 years).ConclusionAMH is independently associated with natural menopause. AMH appears most useful in identifying women at risk of menopause in the near future (within 3 years of AMH measurement).     

Hepatic mitochondrial dysfunction in senescence-accelerated mice: correction by long-term,orally administered physiological levels of melatonin

Mitochondrial oxidative damage from free radicals may be a factor underlying aging. We investigated whether long-term administration of physiological levels of melatonin, a direct free radical scavenger and indirect antioxidant, influences mitochondrial respiratory activity in liver of senescence-accelerated mice (SAM). Liver was obtained in the middle of dark period of the daily light:dark cycle from SAMP8, a strain of mice prone to accelerated senescence, and from SAMR1, a senescence-resistant strain, at 6 and 12 months of age. Respiratory control index (RCI), adenosine-5-diphosphate (ADP)/O ratio, State 3 respiration and dinitophenol (DNP)-dependent uncoupled respiration exhibited significant age-associated decreases in SAMP8. SAMP8 also showed significant age-associated reductions in respiratory chain complex I and IV activities. No age-related effects were found in these parameters in SAMR1. Daily oral melatonin administration (2 microg/mL of drinking fluid) beginning at 7 months of age significantly increased RCI, State 3 respiration, DNP-dependent uncoupled respiration, and complex I and IV activities in both mouse strains when they were 12 months old. These results reveal age-related reductions in mitochondrial function in SAM mice which are modified by melatonin; the most likely explanation for the corrective actions of melatonin relate to its antioxidative actions in mitochondria and other portions of the cell. The implication of the findings is that melatonin may be beneficial during aging as it reduces the deteriorative oxidative changes in mitochondria and other portions of the cell associated with advanced age.     

Age-related changes in working memory and the ability to ignore distraction

A weakened ability to effectively resist distraction is a potential basis for reduced working memory capacity (WMC) associated with healthy aging. Exploiting data from 29,631 users of a smartphone game, we show that, as age increases, working memory (WM) performance is compromised more by distractors presented during WM maintenance than distractors presented during encoding. However, with increasing age, the ability to exclude distraction at encoding is a better predictor of WMC in the absence of distraction. A significantly greater contribution of distractor filtering at encoding represents a potential compensation for reduced WMC in older age.The number of items that can be held in working memory (WM) declines with increasing age (1). Our ability to effectively exclude distractors is one basis for this limited working memory capacity (WMC) (2, 3), with impaired inhibitory processing of distraction contributing to an age-related reduction in WM performance (4). A specific impairment in suppressing distractor representations in older adults has been linked to reduced WMC (5). Typically distractors are presented either with the items to be remembered (encoding distraction, ED, e.g., 6, 7) or while these items are held in mind (delay distraction, DD, e.g., 5, 8). We recently highlighted a distinction between the effects of these two types of distraction in younger adults (9). Although greater WMC is associated with an enhanced ability to exclude distractors in both cases, each makes a unique contribution to WMC (9). Here we examine the well-known age-related reduction in WMC. Previous work has identified an age-related delay in ED filtering (7) and an early age-related deficit in DD suppression (8). We directly compare the age-related decline in ED and DD to assess whether an ability to ignore a distraction at encoding or at delay provides the best predictor of general WMC.We obtained data from 29,631 users of a smartphone game (part of The Great Brain Experiment, www.thegreatbrainexperiment.com), a platform that has enabled us to replicate a range of laboratory studies (9, 10). Using this medium we implemented a WM task to enable us to directly compare the effects of age on WM in the absence of distractors (no distraction, ND; Fig. 1A), when distractors are presented at encoding (ED; Fig. 1B) and when distractors are presented during maintenance (DD; Fig. 1C). This large subject pool enabled us to consider data from six age groups (18–24 y: n = 7,658; 25–29 y: n = 5,702; 30–39 y: n = 8,225; 40–49 y: n = 4,667; 50–59 y: n = 2,359; and 60–69 y: n = 1,020). For each condition the number of items to be remembered (WM load) increased as a function of performance until either eight trials had been completed or a participant failed two successive trials of a given WM load. Data were excluded from participants who failed a “load 2” trial in any condition. For each condition, the participant’s score represents the maximum number of items for which they could report all items successfully, representing their WMC.Open in a separate windowFig. 1.The smartphone game. Red circles are presented simultaneously, followed by a delay of 1 s. Participants should then indicate the positions of the red circles. (A) No distraction (ND) condition; only red circles are shown. (B) Encoding distraction (ED) condition; two yellow circles (distractors) are presented with the red circles. (C) Delay distraction (DD) condition; two yellow circles (distractors) are presented during the delay.     

Development and aging of cortical thickness correspond to genetic organization patterns

There is a growing realization that early life influences have lasting impact on brain function and structure. Recent research has demonstrated that genetic relationships in adults can be used to parcellate the cortex into regions of maximal shared genetic influence, and a major hypothesis is that genetically programmed neurodevelopmental events cause a lasting impact on the organization of the cerebral cortex observable decades later. Here we tested how developmental and lifespan changes in cortical thickness fit the underlying genetic organizational principles of cortical thickness in a longitudinal sample of 974 participants between 4.1 and 88.5 y of age with a total of 1,633 scans, including 773 scans from children below 12 y. Genetic clustering of cortical thickness was based on an independent dataset of 406 adult twins. Developmental and adult age-related changes in cortical thickness followed closely the genetic organization of the cerebral cortex, with change rates varying as a function of genetic similarity between regions. Cortical regions with overlapping genetic architecture showed correlated developmental and adult age change trajectories and vice versa for regions with low genetic overlap. Thus, effects of genes on regional variations in cortical thickness in middle age can be traced to regional differences in neurodevelopmental change rates and extrapolated to further adult aging-related cortical thinning. This finding suggests that genetic factors contribute to cortical changes through life and calls for a lifespan perspective in research aimed at identifying the genetic and environmental determinants of cortical development and aging.There is a growing realization that events during development impact brain and cognition throughout the entire lifespan (1). For instance, the major portion of the relationship between cortical thickness and IQ in old age can be explained by childhood IQ (2), and genotype may explain a substantial part of the lifetime stability in intelligence (3). Effects of genes on the organization of the cortex have been shown in adults (4–6), but it is unknown whether and how regional differences in cortical development correspond to these regional genetic subdivisions.Although consensus has not been reached for the exact trajectories, cortical thickness as measured by MRI appears to decrease in childhood (7–12). The exact foundation for this thinning is not known, as MRI provides merely representations of the underlying neurobiology, and available histological data cannot with certainty be used to guide interpretations of MRI results. Although speculative, apparent thickness decrease may be grounded in factors such as synaptic pruning and intracortical myelination, although the link between established synaptic processes (13–15) and cortical thickness has not been empirically confirmed. After childhood, cortical thinning continues throughout the remainder of the lifespan, speculated to reflect neuronal shrinkage and reductions in number of spines and synapses (16), although similar to development, we lack data to support a direct connection between cortical thinning and specific neurobiological events.It has been demonstrated that genetic correlations between thickness in different surface locations can be used to parcellate the adult cortex into regions of maximal shared genetic influence (4). This result can be interpreted according to the hypothesis that genetically programmed neurodevelopmental events cause lasting impact on the organization of the cerebral cortex detectable decades later (4–6). Here we tested how developmental and lifespan changes fit the genetic organization of cortical thickness in a large longitudinal sample with 1,633 scans from 974 participants between 4.1 and 88.5 y of age, including 773 scans from children below 12 y Genetically based subdivisions of cortical thickness from an independent dataset of 406 twins (4) were applied to the data, yielding 12 separate regions under maximum control of shared genetic influences. We hypothesized that thickness in cortical regions with overlapping genetic architecture would show similar developmental and adult age change trajectories and dissimilar trajectories for regions with low genetic overlap.     

Exogenous Hsp70 delays senescence and improves cognitive function in aging mice

Molecular chaperone Heat Shock Protein 70 (Hsp70) plays an important protective role in various neurodegenerative disorders often associated with aging, but its activity and availability in neuronal tissue decrease with age. Here we explored the effects of intranasal administration of exogenous recombinant human Hsp70 (eHsp70) on lifespan and neurological parameters in middle-aged and old mice. Long-term administration of eHsp70 significantly enhanced the lifespan of animals of different age groups. Behavioral assessment after 5 and 9 mo of chronic eHsp70 administration demonstrated improved learning and memory in old mice. Likewise, the investigation of locomotor and exploratory activities after eHsp70 treatment demonstrated a significant therapeutic effect of this chaperone. Measurements of synaptophysin show that eHsp70 treatment in old mice resulted in larger synaptophysin-immunopositive areas and higher neuron density compared with control animals. Furthermore, eHsp70 treatment decreased accumulation of lipofuscin, an aging-related marker, in the brain and enhanced proteasome activity. The potential of eHsp70 intranasal treatment to protect synaptic machinery in old animals offers a unique pharmacological approach for various neurodegenerative disorders associated with human aging.Heat shock proteins (HSPs) serve to maintain intracellular protein homeostasis and have been shown to prevent protein damage during aging in different animal models (1). HSPs are required for longevity (2, 3), and a number of studies suggest that longer-lived species have higher constitutive expression of HSPs (4–7). Consistent with this finding, overexpression of HSP genes increased longevity in Drosophila, Caenorhabditis elegans, and vertebrates (1, 8, 9). Hsp70 is the major cytoprotective molecular chaperone with many different functions in the cell (10–12). Observations suggest that genetic variants of the Hsp70 family contribute to longevity in a wide range of organisms (9, 13, 14). Its defensive role in multiple neurodegenerative disorders (15, 16) can be explained by the multifaceted action of this protein. Indeed, the induction of Hsp70 has been shown to diminish oxidative stress damage (17, 18), suppress apoptosis (19), support proteasomal and lysosomal functioning (20), suppress toxic protein aggregation such as Aβ (21), inhibit proinflammatory signaling (22), and increase survival of endogenous neural progenitor cells (21). Notwithstanding Hsp70’s importance, its chaperone activity, as well as the rate of its synthesis and induction in response to stimuli, decreases in neurons with age (3, 6, 21, 22), suggesting that a pharmacological approach aiming to recover this chaperone in the aging brain may counter neurodegeneration.To our knowledge, the effect of exogenous HSPs on longevity has not yet been investigated. We previously showed that intranasally injected Hsp70 rapidly entered the brain of wild-type mice and was transported within neurons (23, 24). Furthermore, chronic Hsp70 treatment ameliorated multiple behavioral and molecular disturbances in two models of Alzheimer’s disease (AD)-type neurodegeneration (23). In this study, we explored the geroprotection potential of recombinant exogenous Hsp70 (eHsp70) in healthy mice. For all of the described experiments, we used highly pure LPS-free human eHsp70 (25), which rules out a possibility of confounding inflammatory responses associated with contaminated Hsp70. Our results demonstrate that long-term intranasal administration of human eHsp70 improves longevity and ameliorates aging-related behavioral deficits and molecular alterations to synaptic structure in the brains of aging mice.