Function In Old Age Research Articles

Relation of Hemoglobin to Level of Cognitive Function in Older Persons

Background: While decreased hemoglobin concentration is common in the elderly, the relationship of the entire range of hemoglobin concentrations with cognitive function is not well understood. Methods: Cross-sectional analyses were conducted utilizing data from community-dwelling, older persons participating in the Rush Memory and Aging Project. Proximate to first available hemoglobin measurement, 21 cognitive tests were administered to measure global cognitive function along with semantic memory, episodic memory, working memory, perceptual speed and visuospatial abilities. Results: For 793 participants without clinical dementia, stroke or Parkinson’s disease, the mean age was 81.0 years (SD = 7.2); 595 (75%) were women, and 94% were white. The mean hemoglobin concentration was 13.3 g/dl (SD = 1.3). 17% of the cohort had anemia. Using linear regression models adjusted for age, education, gender, body mass index, mean corpuscular volume and glomerular filtration rate, both low and high hemoglobin levels were associated with lower global cognitive function (parameter estimate = –0.015, SE = 0.007, p = 0.019). Low and high hemoglobin levels were associated with worse performance on semantic memory (parameter estimate = –0.201, SE = 0.008, p = 0.010) and perceptual speed (parameter estimate = –0.030, SE = 0.010, p = 0.004), but not the other specific cognitive functions. Conclusions: Low and high hemoglobin concentrations in older persons are associated with a lower level of cognitive function in old age, particularly in semantic memory and perceptual speed.

Measuring renal function in old age

Accurate assessment of renal function is vital, especially in older individuals, as this is the population in which the greatest burden of chronic kidney disease (CKD) occurs. With ageing, the kidneys undergo a multitude of structural and functional changes. The age-related changes in the kidneys may be further complicated by concurrent pre-renal, renal and post-renal factors common in old age, such as hypertensive glomerulosclerosis, diabetic nephropathy, congestive cardiac failure, renovascular atheroma, urinary outflow obstruction, urinary tract infections, renal stones and drug-induced nephrotoxicity. Structurally, there is a progressive loss of predominantly cortical renal mass, a decrease in the number of glomeruli, an increase in the proportion of sclerotic glomeruli, tubulo-interstitial changes resulting in fibrosis and atrophy, arteriosclerotic vascular changes and a reduction in renal blood flow. Excretory and reabsorptive capacities of the renal tubules may also decline with ageing. Functionally, although there may be a decline in the glomerular filtration rate (GFR) resulting primarily from a reduction in the number of functioning nephrons, this decline may not be universal. Up to a third of elderly people may not demonstrate a decline in GFR with ageing, whilst in some individuals GFR may actually increase with age.

Use of benzodiazepines, depressive symptoms and cognitive function in old age

Benzodiazepine use is more frequently observed in depressive and cognitively impaired subjects. The temporal relation behind this association is unknown. Here, we studied whether benzodiazepine use is associated with depressive symptoms and cognitive function and what the temporal relation underlying the associations is. Within the Leiden 85-plus Study, a prospective population based study of 599 subjects aged 85 years at baseline, we assessed benzodiazepine use, depressive symptoms, and cognitive function annually during a 5-year follow-up period. Benzodiazepine users were more likely to be female, be institutionalized, and have a low education. Benzodiazepine users scored 0.76 points higher on the 15-item Geriatric Depression Scale than non-users (95% CI: 0.27-1.25, p = 0.002). They were 1.6-fold more likely to develop new depressive symptoms in 1 year when compared to non-users (95% CI: 1.05-2.55, p = 0.028). Benzodiazepine use did not associate with cognitive function, but discontinued benzodiazepine users had a 4.0 points lower Mini Mental State Examination (MMSE) score in the year before discontinuation than continued benzodiazepine users (95% CI: 1.31-6.73, p = 0.004). In old age the use of benzodiazepines is associated with depressive symptoms and the use of benzodiazepines may precede the development of depressive symptoms. Treating physicians seem to be aware of the detrimental effects of benzodiazepines on cognitive function. However, they should be cautious in prescribing a new benzodiazepine in old age and monitor elderly benzodiazepine users for development of depressive symptoms.

Enrichment Effects on Adult Cognitive Development: Can the Functional Capacity of Older Adults Be Preserved and Enhanced?

Enrichment Effects on Adult Cognitive Development: Can the Functional Capacity of Older Adults Be Preserved and Enhanced?

Prediction of 3-Dimensional Structure of Cathepsin L Protein of Rattus Norvegicus

Cathepsin L is a cysteine protease which degrades connective tissue proteins like collagen, elastin and fibronectin. Increase in the expression of cathepsin L in aged kidney leading to considerable loss of organ function in old age. Recently it has been reported that SARS-CoV or SARS-CoV spike protein-pseudotyped retroviruses utilize the enzymatic activity of endosomal cathepsin L protease for viral entry. A 3D structure of rat cathepsin L was constructed in this report through homology modeling using the X-ray structure of procathepsin L from Homo sapiens (PDB code: 1CS8). The homology modeling was done by using the MODELLER 9v2 software. The final model obtained by molecular mechanics and dynamics method and was assessed by PROCHECK and VERIFY 3D graph, which showed that the final refined model is reliable. The model could be further explored for characterizing the protein.

Vertigo and falls in the elderly

In many acute or chronic vestibular diseases in old age, the risk of falling is increased. A fear of falling often develops together with further limitations to physical activity and subsequent physical and psychological consequences. Falls represent a substantial health-related risk factor. A regular balance, walking and muscle training is an effective prophylaxis. Components of the treatment of vestibular diseases in old age are counselling and encouragement (psychotherapy), treatment of the specific organic disease, specific vestibular rehabilitation and a symptomatic medication therapy. Vertigo in old age is a multifactorial process. The differential diagnosis of disorders of the equilibrium function in old age represents a challenge which can only be overcome by interdisciplinary cooperation.

A random change point model for assessing variability in repeated measures of cognitive function

Some cognitive functions undergo transitions in old age, which motivates the use of a change point model for the individual trajectory. The age when the change occurs varies between individuals and is treated as random. We illustrate the properties of a random change point model and use it for data from a Swedish study of change in cognitive function in old age. Variance estimates are obtained from Markov chain Monte Carlo simulation using Gibbs sampling. The random change point model is compared with models within the family of linear random effects models. The focus is on the ability to capture variability in measures of cognitive function. The models make different assumptions about the variance over the age span, and we demonstrate that the random change point model has the most reasonable structure.

Social Competitiveness and Plasticity of Neuroendocrine Function in Old Age: Influence of Neonatal Novelty Exposure and Maternal Care Reliability

Early experience is known to have a profound impact on brain and behavioral function later in life. Relatively few studies, however, have examined whether the effects of early experience remain detectable in the aging animal. Here, we examined the effects of neonatal novelty exposure, an early stimulation procedure, on late senescent rats' ability to win in social competition. During the first 3 weeks of life, half of each litter received daily 3-min exposures to a novel environment while the other half stayed in the home cage. At 24 months of age, pairs of rats competed against each other for exclusive access to chocolate rewards. We found that novelty-exposed rats won more rewards than home-staying rats, indicating that early experience exerts a life-long effect on this aspect of social dominance. Furthermore, novelty-exposed but not home-staying rats exhibited habituation of corticosterone release across repeated days of social competition testing, suggesting that early experience permanently enhances plasticity of the stress response system. Finally, we report a surprising finding that across individual rat families, greater effects of neonatal novelty exposure on stress response plasticity were found among families whose dams provided more reliable, instead of a greater total quantity of, maternal care.

Aging‐related changes in astrocytes in the rat retina: imbalance between cell proliferation and cell death reduces astrocyte availability

The aim of this study was to investigate changes in astrocyte density, morphology, proliferation and apoptosis occurring in the central nervous system during physiological aging. Astrocytes in retinal whole-mount preparations from Wistar rats aged 3 (young adult) to 25 months (aged) were investigated qualitatively and quantitatively following immunofluorohistochemistry. Glial fibrillary acidic protein (GFAP), S100 and Pax2 were used to identify astrocytes, and blood vessels were localized using Griffonia simplicifolia isolectin B4. Cell proliferation was assessed by bromodeoxyuridine incorporation and cell death by TUNEL-labelling and immunolocalization of the apoptosis markers active caspase 3 and endonuclease G. The density and total number of parenchymal astrocytes in the retina increased between 3 and 9 months of age but decreased markedly between 9 and 12 months. Proliferation of astrocytes was detected at 3 months but virtually ceased beyond that age, whereas the proportion of astrocytes that were TUNEL positive and relative expression of active caspase 3 and endonuclease G increased progressively with aging. In addition, in aged retinas astrocytes exhibited gliosis-like morphology and loss of Pax2 reactivity. A small population of Pax2(+)/GFAP(-) cells was detected in both young adult and aged retinas. The reduction in the availability of astrocytes in aged retinas and other aging-related changes reported here may have a significant impact on the ability of astrocytes to maintain homeostasis and support neuronal function in old age.

The Oldest Old: Missed Public Health Opportunities

The fastest growing segment of our population is the “oldest old,” usually defined as those 85 years and older. In 2005, this group numbered more than 5 million persons, or about 1.7% of the US population, a 40% increase since 1990. Because the oldest old carry a greater burden of disease and disability, they account for a substantial proportion of health care spending, with total annual per capita health care costs of $25691. A higher proportion of health care spending in this population is partially attributable to long-term services—most notably, nursing home care. As our population ages, substantial concerns have been expressed regarding the future ability of the health care system to provide needed care. Much of this analysis, however, has failed to consider the potential impact of public health strategies to promote health and reduce disability among the old and very old in our population. There is promising evidence that rates of disability and functional dependence among older persons have been decreasing over the last 2 decades, and continue to fall. In this issue of the Journal, Murabito et al. provide data from the Framingham study to show a significant decline in disability among community-dwelling elders from the 1970s to the 1990s. Unfortunately, there are important missed public health opportunities to improve the health and function of older populations. Vaccination for influenza is provided to less than 75% of older persons, and even fewer (60%) have ever received a pneumococcal vaccine. Promotion of healthy behaviors is also crucial. The Type II Diabetes Prevention Trial demonstrated that older persons were able to follow diet and exercise regimens, and that these behavior changes resulted in significant success in prevention of type II diabetes. However, despite the fact that physical activity is associated with important health outcomes at all ages, physical activity declines with age. Only 1 in 5 persons aged 45–64 years engages in vigorous physical activity, and this drops to about 1 in 20 for those over the age of 75 years. To achieve the potential of improved health among the oldest old, as a society we would do well to work together to (1) change public perceptions regarding the benefits of promoting health among older persons, (2) encourage elders to engage in healthier behaviors, (3) improve the practices of health providers, (4) stimulate health departments and service agencies to provide health promotion services, and (5) include public health and aging in education of public health professionals. Despite the importance of improving health behaviors across the life span to achieve optimal health and function in old age, a recent survey of schools of public health reported that fewer than 6% of students participated in a public health and aging course. Moreover, the majority of schools lack a comprehensive and integrated curriculum that adequately addresses health issues in the aging. We have the opportunity to do better for our older population and for ourselves as we age. My 93-year-old grandmother illustrated this perfectly. As she showed us around her senior housing, she pointed out the congregate meals site that she visited on Tuesdays and Thursdays. When I asked if she enjoyed the meals, she pulled herself up to her full 4 feet, 10 inches to indignantly declare that she did not go to eat, but to “help serve the old people.”

P4-106: Cognitive functioning in old age: Temporal trends in a rural area in Sweden

P4-106: Cognitive functioning in old age: Temporal trends in a rural area in Sweden

The influence of age on the association between cholesterol and cognitive function

With the increasing emphasis on vascular disease as a risk factor for dementia and cognitive impairment, lowering cholesterol has received much attention to maintain cognitive function. Observational studies have shown that high total serum cholesterol levels in middle age, but not in old age, associate with cognitive impairment in later life. This can be explained in part since the association between high levels of total serum cholesterol levels and cardiovascular disease becomes weaker with increasing age and is absent in old age. Most studies on HDL-cholesterol levels show a protective association with cardiovascular disease up to old age, whereas data on the protective association with late-life cognitive impairment is absent. In contrast to general belief, randomized controlled trials and most longitudinal observational studies do not show a positive effect of statin treatment on the risk of dementia when prescribed in later life. In conclusion, high total serum cholesterol in middle age is associated with cognitive impairment and statin therapy is likely to have a benefit on cognitive function via a decrease of cardiovascular pathologies. However, a beneficial effect of cholesterol lowering on cognitive function in old age is uncertain.

Acute and long-term associations between ApoE genetic polymorphism, cortisol levels, and declarative memory performance in older adults

For the past two decades, researchers have shown that elevated levels of circulating stress hormones may negatively impact cognitive performance in older adults. As well, genetic polymorphism of the apolipoprotein E gene (APOE) has been found to contribute to impairment in cognitive performance in old age. To date, only one study has reported a relationship between APOE status and cortisol levels, however the relationship was only found to be significant in dementia patients, with a trend observed in healthy controls. The goal of the present investigation was to examine the acute and long-term relationship between APOE status, cortisol secretion, and declarative memory performance in older adults. Two sample cohorts were assessed. In the first cohort, 24-h basal serum cortisol levels were obtained once a year over eight years to assess changes in basal cortisol levels over time. Declarative memory was also obtained in this group at three time-points over five years. In the second cohort, basal and stress-induced cortisol levels as well as basal declarative memory was tested. In the first cohort, E4 carriers were found to secrete higher serum cortisol levels than non-E4 carriers during the first 24-h visit (p=0.04) to the laboratory. However, this group difference did not remain over subsequent years. Furthermore, declarative memory performance over years did not significantly differ according to APOE status. In the second cohort, no significant group differences were found for basal or reactive cortisol levels (ps>0.05), and no group difference was found for acute declarative memory performance. The findings in this study suggest minimal to no significant effect of APOE status on cortisol secretion or declarative memory in non-demented older adults.

Hans-Werner Wahl, Clemens Tesch-Romer and Andreas Hoff (eds.) (2007). New Dynamics in Old Age: Individual, Environmental and Societal Perspectives. New York: Baywood Publishing Co., 400 pp. ISBN 0-89503-322-4 (hpk)

New Dynamics in Old Age represents an outstanding edited collection of scholarship on aging for the twenty-first century. The key aim is to critically examine changes that have affected aging since the Second World War while looking ahead to the changes on the horizon in terms of older people’s everyday lives and policies pertaining to older people. A key thesis is that the post-war consensus of welfare policies supporting older people has been broken down by profound societal changes, which through globalisation have affected all western societies to different degrees. The focus is on continuity and change related to aging both at an individual level and as a social process. This theoretically sophisticated set of essays provides evidence that the very concept of aging has taken on a completely new form over recent decades. A key thread is to examine the dynamics of societal discourses about aging, for example relating to older people as a “burden” and “successful aging”, “new aging” and “new agers”. The editors have assembled 20 chapters by a galaxy of leading scholars and researchers within the field of aging from the US and northwest Europe. The focus is primarily western research on aging, drawing on disciplines from across social gerontology, including from sociology, social psychology, and social policy. The introductory section includes a notable chapter by Kenneth Manton and XiLuang Gu on changes in physical and mental functioning in old age, illustrating the major reduc

Typical Intellectual Engagement and Cognition in Old Age

ABSTRACT Typical Intellectual Engagement (TIE) comprises the preference to engage in cognitively demanding activities and has been proposed as a potential explanatory variable of individual differences in cognitive abilities. Little is known, however, about the factorial structure of TIE, its relations to socio-demographic variables, and its influence on intellectual functioning in old age. In the present study, data of 364 adults (65–81 years) from the Zurich Longitudinal Study on Cognitive Aging (ZULU) were used to investigate the factorial structure of TIE and to examine the hypothesis that TIE is associated more strongly with crystallized intelligence than with fluid intelligence in old age. A measurement model of a second order factor based on a structure of four correlated first order factors (Reading, Problem Solving, Thinking, and Intellectual Curiosity) evinced an excellent fit. After controlling for age, sex, and formal education, TIE was more strongly associated with crystallized intelligence than with fluid intelligence, comparable to results in younger persons. More detailed analyses showed that this association is mostly defined via Reading and Intellectual Curiosity.

Mental Health and Cognitive Function in Adults Aged 18 to 92 Years

We investigated mental health and cognitive function in 195 community-dwelling adults aged 18 to 92 years (M = 46.64). We assessed several cognitive domains, including psychomotor, executive function, and episodic memory. We found a significant Age x Mental Health interaction in relation to within-person (WP) variability (trial-to-trial variability in reaction time performance) in a four-choice psychomotor task and a Stroop task, but not in relation to mean reaction time measures from those tasks. Poorer mental health was associated with greater WP variability in older adults. We did not find this effect in relation to memory. The findings suggest that measures of WP variability may be sensitive to relatively subtle effects associated with age and poor mental health, and that they provide valuable insights into cognitive function in old age.

Genetic variation in the interleukin-1 -converting enzyme associates with cognitive function. The PROSPER study

Inflammation is thought to play an important role in the development of cognitive decline and dementia in old age. The interleukin-1 signalling pathway may play a prominent role in this process. The gene encoding for interleukin-1 beta-converting enzyme (ICE) is likely to influence IL-1 beta levels. Inhibition of ICE decreases the age-related increase in IL-1 beta levels and may therefore improve memory function. We assessed whether genetic variation in the ICE gene associates with cognitive function in an elderly population. All 5804 participants of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) were genotyped for the 10643GC, 9323GA, 8996AG and 5352GA polymorphisms in the ICE gene. Cross-sectional associations between the polymorphisms and cognitive function were assessed with linear regression. Longitudinal associations between polymorphisms, haplotypes and cognitive function were assessed with linear mixed models. All associations were adjusted for sex, age, education, country, treatment with pravastatin and version of test where appropriate. Subjects carrying the variants 10643C and 5352A allele had significantly lower IL-1 beta production levels (P < 0.01). Furthermore, we demonstrated that homozygous carriers of the 10643C and the 5352A allele performed better on all executive function tests at baseline and during follow-up compared to homozygous carriers of the wild-type allele (all P < 0.02). The haplotype with two variants present (10643C and 5352A) was associated with better executive function (all P < 0.02) compared to the reference haplotype without variants. For memory function the same trend was observed, although not significant. Genetic variation in the ICE gene is associated with better performance on cognitive function and lower IL-1 beta production levels. This suggests that low levels of IL-1 beta are protective for memory and learning deficits. Inhibition of ICE may therefore be an important therapeutic target for maintaining cognitive function in old age.

Einstellungen zum eigenen Altern: Eine Alters- oder eine Ressourcenfrage?

Recent studies have demonstrated that positive and negative stereotypes and attitudes toward age and aging may have substantial effects on the longterm development of cognitive and physical performance in old age. Relatively little is known to which degree attitudes toward one's own aging depend on (a) the current level of individual resources, (b) changes in the level of individual resources, or (c) the increasing age of older persons. The present study examined the relations between individual physical, mental, and cognitive resources and the attitudes toward one's own aging. The study was conducted with N=500 participants of the Interdisciplinary Longitudinal Study of Adult Development (ILSE) born between 1930 and 1932 (age: M=63.0, SD=0.9 at T1 and M=66.9, SD=0.9 at T2). The results indicate that the attitudes toward one's own aging (a) become more negative with increasing age, (b) most strongly depend on the available resources, (c) changes in level of resources contribute to the prediction of the attitudes toward one's own aging, and (d) age acts more as a reinforcing factor on the relation between resources and attitudes than as an independent factor on the attitudes toward one's own aging.

Genetic contributions to age-related decline in executive function: a 10-year longitudinal study of COMT and BDNF polymorphisms

Genetic variability in the dopaminergic and neurotrophic systems could contribute to age-related impairments in executive control and memory function. In this study we examined whether genetic polymorphisms for catechol-O-methyltransferase (COMT) and brain-derived neurotrophic factor (BDNF) were related to the trajectory of cognitive decline occurring over a 10-year period in older adults. A single-nucleotide polymorphism (SNP) in the COMT (Val158/108Met) gene affects the concentration of dopamine in the prefrontal cortex. In addition, a Val/Met substitution in the pro-domain for BDNF (Val66Met) affects the regulated secretion and trafficking of BDNF with Met carriers showing reduced secretion and poorer cognitive function. We found that impairments over the 10-year span on a task-switching paradigm did not vary as a function of the COMT polymorphism. However, for the BDNF polymorphism the Met carriers performed worse than Val homozygotes at the first testing session but only the Val homozygotes demonstrated a significant reduction in performance over the 10-year span. Our results argue that the COMT polymorphism does not affect the trajectory of age-related executive control decline, whereas the Val/Val polymorphism for BDNF may promote faster rates of cognitive decay in old age. These results are discussed in relation to the role of BDNF in senescence and the transforming impact of the Met allele on cognitive function in old age.

Human aging magnifies genetic effects on executive functioning and working memory

We demonstrate that common genetic polymorphisms contribute to the increasing heterogeneity of cognitive functioning in old age. We assess two common Val/Met polymorphisms, one affecting the Catechol-O-Methyltransferase (COMT) enzyme, which degrades dopamine (DA) in prefrontal cortex (PFC), and the other influencing the brain-derived neurotrophic factor (BDNF) protein. In two tasks (Wisconsin Card Sorting and spatial working memory), we find that effects of COMT genotype on cognitive performance are magnified in old age and modulated by BDNF genotype. Older COMT Val homozygotes showed particularly low levels of performance if they were also BDNF Met carriers. The age-associated magnification of COMT gene effects provides novel information on the inverted U-shaped relation linking dopaminergic neuromodulation in PFC to cognitive performance. The modulation of COMT effects by BDNF extends recent evidence of close interactions between frontal and medial-temporal circuitries in executive functioning and working memory.