Cognitive Decline

This meta-analysis of 28 data sets (N ¼ 705 older adults, N ¼ 962 younger adults) examined age differences in emotion recognition across four modalities: faces, voices, bodies/contexts, and matching of faces to voices. The results indicate that older adults have increased difficulty recognising at least some of the basic emotions (anger, sadness, fear, disgust, surprise, happiness) in each modality, with some emotions (anger and sadness) and some modalities (face-voice matching) creating particular difficulties. The predominant pattern across all emotions and modalities was of age-related decline with the exception that there was a trend for older adults to be better than young adults at recognising disgusted facial expressions. These age-related changes are examined in the context of three theoretical perspectives-positivity effects, general cognitive decline, and more specific neuropsychological change in the social brain. We argue that the pattern of age-related change observed is most consistent with a neuropsychological model of adult aging stemming from changes in frontal and temporal volume, and/or changes in neurotransmitters. r

Cognitive impairment can be influenced by a number of factors. The potential effect of nutrition has become a topic of increasing scientific and public interest. In particular, there are arguments that nutrients (food and/or supplements) such as vitamins, trace minerals, lipids, can affect the risk of cognitive decline and dementia, especially in frail elderly people at risk of deficiencies. Our objective in this paper is to review data relating diet to risk of cognitive decline and dementia, especially Alzheimer's disease (AD). We chose to focus our statements on homocysteine-related vitamins (B-vitamins), antioxidant nutrients (vitamins E and C, carotenoids, flavonoids, enzymatic cofactors) and dietary lipids. Results of epidemiological studies may sometimes appeared conflicting; however, certain associations are frequently found. High intake of saturated and trans-unsaturated (hydrogenated) fats were positively associated with increased risk of AD, whereas intake of polyunsaturated and monounsaturated fats were protective against cognitive decline in the elderly in prospective studies. Fish consumption has been associated with lower risk of AD in longitudinal cohort studies. Moreover, epidemiologic data suggest a protective role of the B-vitamins, especially vitamins B9 and B12, on cognitive decline and dementia. Finally, the results on antioxidant nutrients may suggest the importance of having a balanced combination of several antioxidant nutrients to exert a significant effect on the prevention of cognitive decline and dementia, while taking into account the potential adverse effects of these nutrients. There is no lack of attractive hypotheses to support research on the relationships between nutrition and cognitive decline. It is important to stress the need to develop further prospective studies of sufficiently long duration, including subjects whose diet is monitored at a sufficiently early stage or at least before disease or cognitive decline exist. Metaanalyses should be developed, and on the basis of their results the most appropriate interventional studies can be planned. These studies must control for the greatest number of known confounding factors and take into account the impact of the standard social determinants of food habits, such as the regional cultures, social status, and educational level.

Background: The Cognitive and Emotional Health Project (CEHP) seeks to identify the demographic, social, and biological determinants of cognitive and emotional health in the older adult. As part of the CEHP, a critical evaluation study committee was formed to assess the state of epidemiological research on demographic, social, and biological determinants of cognitive and emotional health. Methods: Criteria for inclusion in the survey were large cohort studies, longitudinal in design, participants predominantly 65 years or older, with measurements of both cognition and emotion, and information on a wide variety of demographic, psychosocial, and biological factors. North American and European studies, which met these criteria, were selected for the review. Outcome measures included cognition, cognitive decline, and cognitive function. For emotion, symptoms included depression and anxiety, positive and negative affect, subjective well being, mastery, and resilience. Results: Ninety-six papers were identified that addressed cognitive and emotional outcomes. A large variety of risk factors were consistently identified with cognitive outcomes, particularly those previously associated with increased risk of cardiovascular disease. There was considerable overlap between risk factors for cognitive and emotional outcomes. Conclusion: This review identifies a large number of lifestyle and health behaviors that alter the risk for maintenance of cognitive and emotional health. Large longitudinal cohort studies are a unique source to explore factors associated with cognitive and emotional health. Secondary analyses of these studies should be encouraged as should the development of standardized questionnaires to measure cognitive and emotional health. Future research in this field should study cognitive and emotional health simultaneously.

Ernest Hemingway is one of the most popular and widely acclaimed American writers of the 20th century. His works and life epitomize the image of the hyper-masculine hero, facing the cruelties of life with 'grace under pressure'. Most of his writings have a quasiautobiographical quality, which allowed many commentators to draw comparisons between his personality and his art. Here, we examine the psychological and physical burdens that hindered Hemingway's life and contributed to his suicide. We first take a look at his early years, and review his psychopathology as an adult. A number of authors have postulated specific diagnoses to explain Hemingway's behavior: borderline personality disorder, bipolar disorder, major depression, multiple head trauma, and alcoholism. The presence of hemochromatosis, an inherited metabolic disorder, has also been suggested. We describe the circumstances of his suicide at 61 as the outcome of accumulated physical deterioration, emotional distress and cognitive decline. Special attention is paid to the war wound he suffered in 1918, which seemed to involve a peculiar altered state of consciousness sometimes called 'near-death experience'. The out-of-body experience, paradoxical analgesia and conviction that dying is 'the easiest thing' seemed to influence his future work. The constant presence of danger, death, and violence in his works, as well as the emphasis on the typical Hemingway 'code hero', can all be traced to particular psychological and neurological disorders, as well as his early brush with death.

Cholinergic neuron loss is a cardinal feature of Alzheimer disease. Nerve growth factor (NGF) stimulates cholinergic function, improves memory and prevents cholinergic degeneration in animal models of injury, amyloid overexpression and aging. We performed a phase 1 trial of ex vivo NGF gene delivery in eight individuals with mild Alzheimer disease, implanting autologous fibroblasts genetically modified to express human NGF into the forebrain. After mean follow-up of 22 months in six subjects, no long-term adverse effects of NGF occurred. Evaluation of the Mini-Mental Status Examination and Alzheimer Disease Assessment Scale-Cognitive subcomponent suggested improvement in the rate of cognitive decline. Serial PET scans showed significant (P < 0.05) increases in cortical 18-fluorodeoxyglucose after treatment. Brain autopsy from one subject suggested robust growth responses to NGF. Additional clinical trials of NGF for Alzheimer disease are warranted.

Type 2 diabetes and dementia in the elderly are major public health problems. Cross-sectional studies have suggested that these two conditions may be inter-related, but the nature of this association is uncertain. Causation can only be established through studies with a longitudinal design, taking into account the many potential confounding factors in any study of cognition. A literature search has identified 10 studies (nine population-based and one of case-controlled design) that included a definable diabetic population and assessments of cognitive function at baseline and at follow-up. These 10 studies utilised a combination of domain-specific cognitive assessments and a clinical diagnosis of dementia in the assessment of cognitive function. Diabetes was associated with either an accelerated cognitive decline or an increased incidence of dementia in eight of nine of the population-based studies. One study demonstrated a relationship between diabetes and vascular cognitive impairment, but not with other types of dementia. No association between type 2 diabetes and cognitive decline was demonstrated in the case-controlled study. These studies provide compelling evidence to support the view that people with type 2 diabetes are at increased risk of developing cognitive impairment in comparison with the general population. D

Critical requirements for the hypothesis that executive functioning is a potential mediator of age-related effects on cognitive functioning are that variables assumed to reflect executive functioning represent a distinct construct and that age-related effects on other types of cognitive functioning are reduced when measures of executive functioning are statistically controlled. These issues were investigated in a study involving 261 adults between 18 and 84 years of age. Although age-related effects on various cognitive abilities were substantially reduced after statistical control of the variance in measures hypothesized to represent executive functioning, there was only weak evidence for the existence of distinct constructs corresponding to executive functioning or to aspects of executive control concerned with inhibition, updating, or time sharing.

Aging is associated with progressive losses in function across multiple systems, including sensation, cognition, memory, motor control, and affect. The traditional view has been that functional decline in aging is unavoidable because it is a direct consequence of brain machinery wearing down over time. In recent years, an alternative perspective has emerged, which elaborates on this traditional view of age-related functional decline. This new viewpoint--based upon decades of research in neuroscience, experimental psychology, and other related fields--argues that as people age, brain plasticity processes with negative consequences begin to dominate brain functioning. Four core factors--reduced schedules of brain activity, noisy processing, weakened neuromodulatory control, and negative learning--interact to create a self-reinforcing downward spiral of degraded brain function in older adults. This downward spiral might begin from reduced brain activity due to behavioral change, from a...

This meta-analysis of 28 data sets (N ¼ 705 older adults, N ¼ 962 younger adults) examined age differences in emotion recognition across four modalities: faces, voices, bodies/contexts, and matching of faces to voices. The results indicate that older adults have increased difficulty recognising at least some of the basic emotions (anger, sadness, fear, disgust, surprise, happiness) in each modality, with some emotions (anger and sadness) and some modalities (face-voice matching) creating particular difficulties. The predominant pattern across all emotions and modalities was of age-related decline with the exception that there was a trend for older adults to be better than young adults at recognising disgusted facial expressions. These age-related changes are examined in the context of three theoretical perspectives-positivity effects, general cognitive decline, and more specific neuropsychological change in the social brain. We argue that the pattern of age-related change observed is most consistent with a neuropsychological model of adult aging stemming from changes in frontal and temporal volume, and/or changes in neurotransmitters. r

Background The recently introduced diagnostic label of Mild Cognitive Impairment (MCI) identifies patients with a cognitive decline that is more pronounced than is usual for a person's age and educational level but does not notably interfere with activities of daily living (ADL). The natural course of the syndrome is uncertain although MCI sufferers have a higher risk of developing dementia. Objectives To investigate how patients fulfilling MCI criteria experience and cope with their cognitive decline with the secondary aim to derive key themes for a prospective MCI support-group programme. Methods The grounded theory approach. Results Analysis of guided interviews with eight MCI patients revealed four common themes. Changes related to cognitive abilities, mobility, affect, vitality and somatic complaints. Attributions were numerous and concerned aetiologies such as personality traits and overload of information. Consequences were all negative and concerned the patients themselves such as anxiety and loss of self-confidence, others such as feelings of irritation and anger towards others or activities like abandoning leisure activities. Patients applied emotion-oriented, problem-focused and avoidant coping strategies. Conclusion MCI patients encounter stress-inducing practical, social and psychological difficulties. Based on the current preliminary findings, the key themes for an MCI support-group programme should include the provision of information about the syndrome's causes, course, concomitant symptoms, attributions, social consequences, and available treatments. The impact of receiving an MCI label warrants further investigation.

The purpose of this study was to verify possible cognitive dysfunction in patients with juvenile myoclonic epilepsy (JME) and its relationship to factors related to epilepsy and schooling. Fifty subjects diagnosed with JME and 50 controls underwent neuropsychological assessment evaluating intellectual functions, attention, memory, executive functions, and language. The patients were further divided into two subgroups on the basis of educational level: 611 and >11 years of formal education. Participants diagnosed with JME scored significantly below age-, education-, and gender-matched controls on neuropsychological measures of attention, immediate verbal memory, mental flexibility, control of inhibition, working memory, processing speed, verbal delayed memory, visual delayed memory, naming, and verbal fluency. A positive correlation was observed between duration of epilepsy and cognitive decline. However, in the group of patients with >11 years of education, this correlation was not significant. In this series of patients with JME, neuropsychological evaluation suggests widespread cognitive dysfunction outside the limits of the frontal lobes. The duration of epilepsy correlated with cognitive decline, and patients with higher education manifested less progression of deficits.

A role for vitamin D in brain development and function has been gaining support over the last decade. Multiple lines of evidence suggest that this vitamin is actually a neuroactive steroid that acts on brain development, leading to alterations in brain neurochemistry and adult brain function. Early deficiencies have been linked with neuropsychiatric disorders, such as schizophrenia, and adult deficiencies have been associated with a host of adverse brain outcomes, including Parkinson's disease, Alzheimer's disease, depression and cognitive decline. This review summarises the current state of research on the actions of vitamin D in the brain and the consequences of deficiencies in this vitamin. Furthermore, we discuss specific implications of vitamin D status on the neurotransmitter, dopamine.

Structural brain changes have been described in both mild cognitive impairment (MCI) and Alzheimer's disease (AD). However, less is known about whether structural changes are detectable earlier, in the asymptomatic phase. Using voxel-based morphometry (VBM) and shape analyses of magnetic resonance imaging (MRI) data, we investigated structural brain differences between groups of healthy subjects, stratified by subsequent diagnoses of MCI or AD during a 10-year follow-up. Images taken at baseline, at least 4 years before any cognitive symptoms, showed that subjects with future cognitive impairment (preclinical AD and MCI) had reduced brain volume in medial temporal lobes, posterior cingulate/precuneus, and orbitofrontal cortex, compared with matched subjects who remained cognitively healthy for 10 years (HC). For only those subjects later diagnosed as AD, significantly greater atrophy at baseline was detected in the right medial temporal lobe, which was also confirmed by shape analysis of the right hippocampus in these subjects. Our results demonstrate that structural brain changes occur years before clinical cognitive decline in AD and are localized to regions affected by AD neuropathology.

AbstractÐWe reviewed epidemiological and experimental studies of female gonadal hormone replacement therapy (HRT) on cognitive function in post-menopausal women and carried out meta-analyses. In healthy ageing women, HRT has small and inconsistent effects that include enhancement of verbal memory, abstract reasoning and information processing. Epidemiological studies show larger effects than experimental studies, which is not related to sample size. Important confounds may be that women who start using HRT are healthier than women who do not. Also, controlling for socio-economic status diminishes the effect of HRT. The effects of HRT may depend on the age and type of menopause and the therapeutic intervention used, with the most widely used drug, Premarin, having least effect. However, the effects are independent of mood and climacteric symptom alleviation. There is a paucity of experimental studies that include healthy elderly women. The evidence for an estrogen de®ciency in women with dementia and cognitive dysfunction is inconsistent. Nevertheless, epidemiological studies suggest that HRT protects against the development of clinically diagnosed Alzheimer's disease. However, poor recall of HRT use by patients and altered physician behaviour may have confounded the effects. Surprisingly, both healthy and demented women with low education seem to bene®t most from HRT. Three recent controlled experimental studies using Premarin showed no effects of HRT in preventing further cognitive decline in women who already have Alzheimer's disease. Duration of treatment seems to play an important role, with bene®cial effects decliningÐand even reversingÐwith longer treatment in women with Alzheimer's disease.

Chemotherapy has improved survival rates in patients with many of the common cancers. However, there is reliable evidence that, as a result of treatment, a subset of cancer survivors experience cognitive problems that can last for many years after the completion of chemotherapy. The etiology of this phenomenon is largely unknown, and currently there are no proven treatments. This article explores the clinical and preclinical literature on potential therapies for chemotherapy-induced cognitive impairments. Emerging results suggest that both pharmacological and behavioral approaches may offer patients some benefits. However, research in this area has been limited and is sometimes fraught with methodological flaws. As a result, it is difficult to draw definite conclusions regarding treatment efficacy. These issues, along with predictors of cognitive decline, are discussed in the light of possible interventions.

Alzheimer's disease (AD) is characterized by cognitive decline and deposition of ␤-amyloid (A␤) plaques in cortex and hippocampus. A transgenic mouse AD model (Tg2576) that overexpresses a mutant form of human A␤ precursor protein exhibits age-related cognitive deficits, A␤ plaque deposition, and oxidative damage in the brain. We tested the ability of Ginkgo biloba, a flavonoid-rich antioxidant, to antagonize the age-related behavioral impairment and neuropathology exhibited by Tg2576 mice. At 8 months of age, 16 female Tg2576 and 15 female wild-type (wt) littermate mice were given ad lib access to tap water or Ginkgo biloba (70 mg/kg/day in water). After 6 months of treatment, all mice received Morris water maze training (4 trials/day for 10 days) to assess hippocampal dependent spatial learning. All mice received a 60-s probe test of spatial memory retention 24 h after the 40th trial. Untreated Tg2576 mice exhibited a spatial learning impairment, relative to wt mice, while Ginkgo biloba-treated Tg2576 mice exhibited spatial memory retention comparable to wt during the probe test. Spatial learning was not different between Ginkgo biloba-treated and untreated wt mice. There were no group differences in learning to swim to a visible platform. Soluble A␤ and hippocampal A␤ plaque burden did not differ between the Tg2576 groups. Brain levels of protein carbonyls were paradoxically elevated in Ginkgo biloba-treated mice. These data indicate that chronic Ginkgo biloba treatment can block an age-dependent decline in spatial cognition without altering A␤ levels and without suppressing protein oxidation in a transgenic mouse model of AD.

Structural magnetic resonance imaging (MRI) studies have shown dramatic age-associated changes in grey and white matter volume, but typically use univariate analyses that do not explicitly test the interrelationship among brain regions. The current study used a multivariate approach to identify covariance patterns of grey and white matter tissue density to distinguish older from younger adults. A second aim was to examine whether the expression of the age-associated covariance topographies is related to performance on cognitive tests affected by normal aging. Eighty-four young (mean age = 24.0) and 29 older (mean age = 73.1) participants were scanned with a 1.5 T MRI machine and assessed with a cognitive battery. Images were spatially normalized and segmented to produce grey and white matter density maps. A multivariate technique, based on the subprofile scaling model, was used to capture sources of between-and within-group variation to produce a linear combination of principal components that represented a "pattern" or "network" that best discriminated between the two age groups. Univariate analyses were also conducted with statistical parametric maps. Grey and white matter covariance patterns were identified that reliably discriminated between the groups with greater than 0.90 sensitivity and specificity. The identified patterns were similar for the univariate and multivariate techniques, and involved widespread regions of the cortex and subcortex. Age and the expression of both patterns were significantly associated with performance on tests of attention, language, memory, and executive functioning. The results suggest that identifiable networks of grey and white matter regions systematically decline with age and that pattern expression is linked to age-related cognitive decline.

The present review integrates findings of published studies that have evaluated the cognitive function of treated and untreated type 2 diabetic patients and provides a detailed overview of the neuropsychological assessments conducted. Cognitive deficits are observed in older people with glucose intolerance or untreated diabetes but these deficits appear to be attenuated by treatments that improve glycemic control. Cognitive decrements in treated type 2 diabetic patients are most consistently observed on measures of verbal memory (35% of the measures) and processing speed (45% of the measures) while preserved function is observed on measures of visuospatial, attention, semantic and language function. Some studies suggest that deficits in cognitive functions are associated with poorer glycemic control. A number of other factors, such as depression, cardiovascular and cerebrovascular disease, increase these deficits. We conclude that, in diabetic patients who achieve and maintain good glycemic control, type 2 diabetes only has a small impact on cognitive functions before the age of 70 years. However, early onset of type 2 diabetes, poor glycemic control and the presence of micro-and macrovascular disease may interact to produce early cognitive deficits. In older adults (70 years and over), diabetes likely interacts with other dementing processes such as vascular disease and Alzheimer's disease to hasten cognitive decline.

This study evaluates transfer from domain-specific, sensorimotor training to cognitive abilities associated with executive function. We examined Individualized Piano Instruction (IPI) as a potential cognitive intervention to mitigate normal age-related cognitive decline in older adults. Thirty-one musically naïve community-dwelling older adults (ages 60-85) were randomly assigned to either the experimental group (n ¼ 16) or control group (n ¼ 15). Neuropsychological assessments were administered at three time points: pre-training, following six months of intervention, and following a three-month delay. The experimental group significantly improved performance on the Trail Making Test and Digit Symbol measures as compared to healthy controls. Results of this study suggest that IPI may serve as an effective cognitive intervention for age-related cognitive decline.

di Cura Major, S. Maugeri Foundation, Turin , Italy between pre-and postoperative neuropsychological test scores showed a signifi cant worsening only in phonemic and semantic verbal fl uency tasks, while fewer errors were found in the Nelson Modifi ed Card Sorting Test. Globally, behavioural assessment evidenced a small improvement in mood, as assessed by the BDI, in obsessive-compulsive and paranoid personality traits (SCID-II). Thought disorders worsened while suicidal ideation, anxiety and apathy showed no postoperative modifi cations. The analysis of individual outcomes ( 8 1 SD criterion) evidenced a relevant postoperative cognitive decline in 3 patients out of 65 (4.5%). Moreover, following implantation, 1 patients exhibited psychosis (1.5%), 2 patients experienced a clinically relevant worsening of depressive symptoms (3%), 7 patients showed an increase in anxiety (12%) and 3 patients a worsening in depression and anxiety symptoms (3%). On the contrary, 12 patients (20%) showed a relevant improvement in mood and 14 patients (23%) a relevant reduction of anxiety symptoms after the surgery. Conclusions: The present study confi rms that STN DBS is cognitively safe since the only relevant change observed was a mild decrease in verbal fl uency tasks. Globally, a small postoperative improvement was found in the BDI, and in two SCID-II subscales concerning obsessive-compulsive and paranoid personality traits, even though postoperative behavioural disturbances can occur in individual patients.

Selenium (Se), a nutritionally essential trace element with known antioxidant potential, protects the brain from oxidative damage in various models of neurodegeneration. Intracerebroventricular-streptozotocin (ICV-STZ) in rats causes impairment of brain glucose and energy metabolism along with oxidative damage and cholinergic dysfunction, and provides a relevant model for sporadic dementia of Alzheimer's type (SDAT). The present study demonstrates the therapeutic efficacy of Se on cognitive deficits and oxidative damage in ICV-STZ in rats. Male Wistar rats were pre-treated with sodium selenite, a salt of Se (0.1 mg/kg; body weight) for 7 days and then were injected bilaterally with ICV-STZ (3 mg/kg), while sham rats received the same volume of vehicle. After two ICV-STZ infusions, rats were tested for memory deficits in passive avoidance and Morris water maze (MWM) tests and then were sacrificed for biochemical and histopatholgical assays. ICV-STZ-infused rats showed significant loss in learning and memory ability, which were significantly improved by Se supplementation. A significant increase in thio-barbituric acid reactive species (TBARS), protein carbonyl (PC) and a significant decrease in reduced glutathione (GSH), antioxidant enzymes (glutathione peroxidase [GPx] and glutathione reductase [GR]) and adenosine triphosphate (ATP) in the hippocampus and cerebral cortex and choline acetyltransferase (ChAT) in hippocampus were observed in ICV-STZ rats. Se supplementation significantly ameliorated all alterations induced by ICV-STZ in rats. Our study reveals that Se, as a powerful antioxidant, prevents cognitive deficits, oxidative damage and morphological changes in the ICV-STZ rats. Thus, it may have a therapeutic value for the treatment of SDAT.

There are no conventional lymphatics in the brain but physiological studies have revealed a substantial and immunologically signiWcant lymphatic drainage from brain to cervical lymph nodes. Cerebrospinal Xuid drains via the cribriform plate and nasal mucosa to cervical lymph nodes in rats and sheep and to a lesser extent in humans.

This paper reviews recent progress in the diagnosis of Alzheimer's disease (AD) from electroencephalograms (EEG). Three major effects of AD on EEG have been observed: slowing of the EEG, reduced complexity of the EEG signals, and perturbations in EEG synchrony. In recent years, a variety of sophisticated computational approaches has been proposed to detect those subtle perturbations in the EEG of AD patients. The paper first describes methods that try to detect slowing of the EEG. Next the paper deals with several measures for EEG complexity, and explains how those measures have been used to study fluctuations in EEG complexity in AD patients. Then various measures of EEG synchrony are considered in the context of AD diagnosis.

Background: Geriatric schizophrenic patients with a chronic course of institutionalization manifest cognitive and functional impairments that implicate decline at some time point after the onset of illness. The rate of change in cognitive and functional status in these patients has not yet been identified with a longitudinal study.

New treatments for Alzheimer's disease require early detection of cognitive decline. Most studies seeking to identify markers of early cognitive decline have focused on a limited number of measures. We sought to establish the profile of brain function measures which best define early neuropsychological decline. We compared subjects with subjective memory complaints to normative controls on a wide range of EEG derived measures, including a new measure of event-related spatio-temporal waves and biophysical modeling, which derives anatomical and physiological parameters based on subject's EEG measurements. Measures that distinguished the groups were then related to cognitive performance on a variety of learning and executive function tasks. The EEG measures include standard power measures, peak alpha frequency, EEG desynchronization to eyes-opening, and global phase synchrony. The most prominent differences in subjective memory complaint subjects were elevated alpha power and an increased number of spatio-temporal wave events. Higher alpha power and changes in wave activity related most strongly to a decline in verbal memory performance in subjects with subjective memory complaints, and also declines in maze performance and working memory reaction time. Interestingly, higher alpha power and wave activity were correlated with improved performance in reverse digit span in the subjective memory complaint group. The modeling results suggest that differences in the subjective memory complaint subjects were due to a decrease in cortical and thalamic inhibitory gains and slowed dendritic time-constants. The complementary profile that emerges from the variety of measures and analyses points to a nonlinear progression in electrophysiological changes from early neuropsychological decline to late-stage dementia, and electrophysiological changes in subjective memory complaint that vary in their relationships to a range of memory-related tasks.

■ Aging is related to cognitive decline, and it has been reported that aging disrupts some resting state brain networks. However, most studies have focused on the default mode network and ignored other resting state networks. In this study, we measured resting state activity using fMRI and explored whether cognitive decline with aging is related to disrupted resting state networks. Independent component analysis was used to evaluate functional connectivity. Notably, the connectivity within the salience network that consisted of the bilateral insula and the anterior cingu-lated cortex decreased with aging; the impairment of functional connectivity was correlated with measured decreases in individual cognitive abilities. Furthermore, certain internetwork connectivities (salience to auditory, default mode to visual, etc.) also decreased with aging. These results suggest that (1) aging affects not only the default mode network but also other networks, specifically the salience network; (2) aging affects internetwork connectivity; and (3) disruption of the salience network is related to cognitive decline in elderly people. ■

PURPOSE: This study examines the association between socio-economic status and cognitive decline in a community-based cohort of well-functioning older adults and seeks to determine whether this link could be explained by biomedical factors. METHODS: Data are from 2574 men and women aged 70 to 79 years from Pittsburgh, PA, and Memphis, TN, participating in the Health, Aging and Body Composition study (Health ABC). Three indicators of socio-economic status were used: education, income, and ownership of financial assets. Cognitive decline over 4 years was defined as a decrease of five points or more in the Modified Mini-Mental State Examination (3MS) score. Biomedical factors measured at baseline, included heart disease, cerebrovascular disease, diabetes, hypertension, poor pulmonary function, and high serum levels of inflammatory markers. RESULTS: Adjusted odds ratios were significantly higher in those with low education, low income, and few assets. Odds ratios ranged from 1.51 to 2.16 in the lowest socio-economic groups. Additional adjustment for biomedical factors reduced the odds ratios of cognitive decline by an average of 2% for education, 5% for income, and 8% for the number of assets. CONCLUSIONS: Low socio-economic status predicts a decline in cognitive function in older adults and this relationship is not mediated by biomedical factors. Ann Epidemiol -;-:-. Ó

Background: The pathological processes underlying cognitive impairment in Parkinson's disease (PD) are heterogeneous and the contribution of cerebral amyloid deposits is poorly defined, particularly in the early stages of the disease. Objective: To investigate regional [ 18 F]florbetaben binding to amyloid-(A) and its contribution to cognitive dysfunction in early stage PD. Methods: A multicenter cohort of 48 PD patients from the Parkinson's Progression Marker Initiative (PPMI) underwent [ 18 F]florbetaben positron emission tomography (PET) scanning. Clinical features, including demographic characteristics, motor severity, cerebrospinal fluid (CSF), and cognitive testing were systematically assessed according to the PPMI study protocol. For the purpose of this study, we analyzed various neuropsychological tests assessing all cognitive functions. Results: There were 10/48 (21%) amyloid positive PD patients (PDA+). Increased [ 18 F]florbetaben uptake in widespread cortical and subcortical regions was associated with poorer performance on global cognition, as assessed by Montreal Cognitive Assessment (MoCA), and impaired performance on Symbol Digit Modality test (SDMT). Further, we found that PDA+ patients had higher CSF total-tau/A 1-42 (p = 0.001) and phosphorylated-tau/A 1-42 in (p = 0.002) compared to amyloid-negative PD.

The efficiency of higher cortical functions, such as memory and speed of complex information processing, tends to decrease with advancing age in normal healthy individuals. Recently, a high habitual intake of caffeine was found associated with better verbal memory performance and psychomotor speed in several cross-sectional population studies. We tested the hypothesis that habitual caffeine intake can reduce or postpone age-related cognitive decline in healthy adults. For this purpose, the cognitive performance of all participants in the Maastricht Aging Study (MAAS), aged between 24 and 81 years, was reassessed after 6 years. Information on the intake of caffeinecontaining beverages was available from the baseline questionnaire. After 6 years, 1376 (75.6%) individuals were available for reassessment. After correction for demographic characteristics, baseline performance and health status, there were small albeit significant associations between the overall estimated caffeine intake at baseline and the 6-year change in complex motor speed (motor choice reaction time). The earlier found association between caffeine intake and verbal memory performance was not apparent in this longitudinal study. These results imply that the longitudinal effect of habitual caffeine intake is limited and will not promote a substantial reduction in age-related cognitive decline at a population level. D

As the majority of the North American population continues to age, cognitive decline in older adults is becoming an ever-growing concern. With the increase in age comes a decrease in cerebral blood flow, slowing of the brain's alpha rhythm and increased theta activity. These changes correlate with reduced cognition, spanning memory, problem solving ability, difficulty with language and speech, and locomotion. Chronic stress impairs hippocampal function leading to a host of disorders including Alzheimer's disease. The left hemisphere of the brain has a tendency to loose functionality before the right side, which may enhance spatial creativity and when coupled with fears and feelings of helplessness, may also bring forth depression. Preliminary studies of Audio-visual entrainment (AVE) have shown this technique to be promising in the treatment of age-related issues common with our senior citizens. AVE is proving to rehabilitate cognitive function in seniors and the best application of AVE may be that as a prophylactic against cognitive decline.

The rate of cognitive decline in Alzheimer’s disease (AD) varies considerably between individuals, with some subjects showing substantial deterioration and others showing little or no change over the course of the disease. These wide variations support the relatively new concept of Rapid Cognitive Decline (RCD). Patients with an accelerated rate of cognitive decline have showed to present a worse evolution in terms of mortality, loss of autonomy and institutionalisation. The conclusions from RCD studies conducted in the past years remain very heterogeneous and sometimes contradictory. This is possibly due to methodological differences, mainly the different “a priori” definitions of RCD used to identify rapid decliners. Consequently of this, there is considerable variation in reported frequency of patients with RCD which may vary from 9.5% to 54%. The lack of both consensus definition and consensual clinical assessment tools is one of the major barriers for establishing an appropriated management of rapid decliners in clinical practice. Presently, management of rapid decliners in AD remains to be a challenge waiting to better know predictive factors of a RCD. To date no specific guidelines exist to follow-up or to treat patients with this condition. This consensus paper proposes the loss of 3 points or greater in Mini-Mental State Examination (MMSE) during six months as an empirical definition of rapid cognitive decline to be used in routine medical practice and to be relevant for clinical-decision making in patients with mild to moderately-severe AD.

Résumé  Le patient âgé fragile est un sujet à haut risque de fracture de hanche. Toutefois, il accède peu à l’organisation aux mesures prévenant la chute et rarement à l’approche diagnostique et thérapeutique de l’ostéoporose. Cette revue de la littérature porte sur les liens entre le syndrome de fragilité et le risque de fracture de hanche. Elle fut discutée lors d’une

This study aimed at exploring metamemory and specifically the accuracy of memory monitoring in mild cognitive impairment (MCI) using an episodic memory feeling-of-knowing (FOK) procedure. To this end, 20 people with MCI and 20 matched control participants were compared on the episodic FOK task. Results showed that the MCI group made less accurate FOK predictions than the control group by overestimating their memory performance on a recognition task. The MCI overestimation behavior was found to be critically related to the severity of their cognitive decline. In the light of recent neuroanatomical models showing the involvement of a temporal-frontal network underlying accurate FOK predictions, the role of memory and executive processes was evaluated. Thus, participants were also administered memory and executive neuropsychological tests. Correlation analysis revealed a between-group differential pattern indicating that FOK accuracy was primarily related to memory abilities in people with MCI, whereas it was specifically related to executive functioning in control participants. The lesser ability of people with MCI to assess their memory status accurately on an episodic FOK task is discussed in relation to both their subjective memory complaints and to their actual memory deficits which might be mediated by the brain vulnerability of their hippocampus and medial temporal system. It is suggested that their memory weakness may lead people with MCI to use other less reliable forms of memory monitoring.

OBJECTIVE: To investigate whether serum cortisol levels are associated with cognitive performance and cognitive decline in elderly persons and whether this association differs by age, sex, and depression status.DESIGN: Data from the Longitudinal Aging Study Amsterdam, with repeated measurements of cognitive performance after 3 and 6 years.PARTICIPANTS: A total of 1,154 persons, aged 65-88 years.MEASUREMENTS: Serum concentrations of total cortisol (CRT) and corticosteroid binding globulin (CBG) were measured at baseline, and from these free cortisol index (CRT/CBG) was computed. At baseline and 3 and 6 years of follow-up, global cognitive functioning, verbal memory performance, and speed of information processing were assessed.RESULTS: After adjustment for demographics, health, and life style variables, a significant association between high levels of free cortisol and poorer performance on verbal learning (B = -0.32; 95% confidence interval: -0.64 to -0.01) was found in both women and men. Additional adjustment for depression did not change this association. In women, but not in men, high levels of free cortisol (B = -0.85; 95% confidence interval: -1.40 to -0.31) were associated with slower speed of information processing. The associations between cortisol and cognitive performance were the same for the younger and the older old and for depressed and nondepressed persons. Higher levels of cortisol were not associated with cognitive decline over a period of 6 years.CONCLUSION: Our study provides further evidence that high levels of cortisol measured during the day are associated with lower memory function and speed of information processing but not with decline in cognitive functioning over 6 years of time.

Objectives Cognitive decline is related to frailty. Frailty can be operationalized in different ways, which have an unknown impact on the estimation of risk. Here, we compared 3 frailty measures in relation to cognitive changes and mortality in the Canadian Study of Health and Aging (CSHA). Design Prospective population-based study, with 5 year follow up. Participants/Setting 2,305 subjects aged 70+ years. Methods For each participant, cognitive status was measured by the errors in the Modified Mini-Mental State Examination (3MS) score. Three frailty measures were used: a Frailty Index based on the Comprehensive Geriatric Assessment (FI-CGA) evaluated from 47 potential deficits, a Clinical Frailty Score and the Fried frailty phenotype. Multivariate Poisson regression and multivariate logistic regression were used to examine the association between baseline cognitive errors and frailty and death, respectively, while controlling for possible confounders (age, sex, education, and baseline cognitive status). Results Changes in cognitive status were strongly associated with baseline cognition and frailty, however defined. In multivariate models adjusted for age, sex and education, each frailty measure was associated with cognitive decline and with mortality. The frailest people (from the highest FI-CGA tertile) rarely showed cognitive improvement or stabilization (1.5%, 95% CI=0.002%–2.8%) compared with non-frail people (from the lowest tertile of the FI-CGA), of whom 27.8% (95% CI=24.5%–31.1%) did not deteriorate. Conclusions Frail elderly people have an increased risk of cognitive decline. All frailty measures allowed quantification of individual vulnerability and predict both cognitive changes and mortality.

The e4 allele of the apolipoprotein E (APOE) gene confers risk of Alzheimer's disease and, in some studies, relates to cognitive ability and decline in older people without Alzheimer's disease. Its relationship with processing speed, a contributor to cognitive decline with age, is largely unknown. This study tests the association of APOE with cognition and speed, with and without covarying childhood mental ability. The 1,013 participants were tested on cognitive ability at age 11 as part of the Scottish Mental Survey of 1947 and, at age 70, were tested on reasoning, working memory, information processing speed, and executive function. The results showed that APOE was associated with the general cognitive factor, 2 nonverbal tests, and choice reaction time (RT) variability; as expected, the e4 allele was the risk allele. RT measures and a general speed factor were nonlinearly related to APOE when factoring childhood ability ( p Ͻ .05): The correlation between childhood ability and speed was lower in e4 allele carriers. APOE has an influence on nonverbal cognition in old age and interacts with childhood IQ to influence processing speed.

Resting state fMRI studies have found that cognitive decline in aging is associated with alterations in functional connectivity of distributed neural systems in the brain. While functional connections have been shown to rely on the underlying structural connectivity, direct structural connections have been studied in only a few distributed cortical systems so far. It is well known that subcortical nuclei have structural connections to the entire cortex. We hypothesized that structural subcortico-cortical connections may provide integral routes for communication between cortical resting state networks, and that changes in the integrity of these connections have a role in cognitive aging. We combined anatomical MRI, diffusion tensor MRI, and resting state fMRI in 100 healthy elderly to identify fiber bundles connecting cortical resting state networks to subcortical nuclei. In identified tracts, white matter fiber bundle integrity measures were compared to composite cognitive measures on executive function, processing speed, and memory performance. The integrity (FA values) in selected fiber bundles correlated strongly with cognitive measures on executive function and processing speed. Correlation was most pronounced between executive function and fiber bundles connecting the putamen to the dorsal attention network (r= 0.73, p b 0.001). Our findings show that unique cortico-subcortical fiber bundles can be identified for a range of cortical resting state networks, and indicate that these connections play an important role in cortical resting state network communication and cognition.

The objective of this study is to identify whether decline in cognitive functioning after chemotherapy in women with breast cancer is associated with health/disease, treatment, and psychological variables. Neuropsychological performance, health/disease, and treatment-related information of 136 women with breast cancer (age M = 49.38; SD = 7.92; range = 25.25-67.92) was assessed pre-chemotherapy and 1-month post-chemotherapy. The Reliable Change Index corrected for practice (RCIp) identifi ed women whose performance signifi cantly declined, while Pearson correlations assessed the relationship between cognitive change and predictor variables. A total of 16.9% of women showed signifi cant decline post-chemotherapy, with affected domains including verbal learning and memory, abstract reasoning, and motor coordination. Decline in hemoglobin levels and increased anxiety over the course of chemotherapy was found to signifi cantly predict impairment in multiple cognitive measures. Change in specifi c cognitive measures was signifi cantly associated with baseline fatigue, depression, and functional well-being ( r = 0.23 to 0.33; p = .01 to < .001). Although the effects are small, there is evidence that psychological and health factors may increase vulnerability to cognitive dysfunction after chemotherapy for breast cancer. Signifi cant associations reported in this study may be useful in the identifi cation and treatment of at-risk individuals. ( JINS , 2009, 15, 951-962.)

Telomeres are nucleo-protein complexes that protect the ends of chromosomes. The telomeric DNA component shortens each time a somatic cell replicates, eventually leading to cell senescence. Telomere length has been associated with morbidity and mortality rates from age-related diseases. We tested the hypotheses that mean peripheral blood leukocyte telomere length, at age 79 years, is associated with physical health at age 79, cognitive ability at age 79, lifetime cognitive change, smoking, alcohol consumption, social class in adulthood, and mortality in a cohort of people without dementia (the Lothian Birth Cohort 1921: LBC1921). There was a small, significant association between telomere length and verbal fluency (a test of executive function) before (r = −0.16, p = 0.027) and after (r = −0.17, p = 0.022) adjustment for mental ability at age 11. This might be a type 1 error. Otherwise, we find that telomere length in old age does not have a significant association with age-related physical and cognitive decline or mortality.

Objectives. Factors accelerating cerebral degenerative changes represent potentially modi®able risks for cognitive decline. Putative risk factors accelerating subtle cognitive decline and dementia were correlated with repeated measures of cerebral atrophy, CT densitometry, perfusions and cognitive testing among neurologically and cognitively normative ageing volunteers.

A growing body of epidemiological evidence suggested that metabolic syndrome (MetS) and Mets components (impaired glucose tolerance, abdominal or central obesity, hypertension, hypertriglyceridemia, and reduced high-density lipoprotein cholesterol) may be important in the development of age-related cognitive decline (ARCD), mild cognitive impairment (MCI), vascular dementia, and Alzheimer's disease (AD). These suggestions proposed in these patients the presence of a "metabolic-cognitive syndrome", i.e. a MetS plus cognitive impairment of degenerative or vascular origin. This could represent a pathophysiological model in which to study in depth the mechanisms linking MetS and MetS components with dementia, particularly AD, and predementia syndromes (ARCD or MCI), suggesting a possible integrating view of the MetS components and their influence on cognitive decline. In the present article, we discussed the role of these factors in the development of cognitive decline and dementia, including underlying mechanisms, supporting their influence on ␤-amyloid peptide metabolism and tau protein hyperphosphorylation, the principal neuropathological hallmarks of AD. In the next future, trials could then be undertaken to determine if modifications of these MetS components including inflammation, another factor probably related to MetS, could lower risk of developing cognitive decline. Future research aimed at identifying mechanisms that underlie comorbid associations of MetS components will not only provide important insights into the causes and interdependencies of predementia and dementia syndromes, but will also inspire novel strategies for treating and preventing cognitive disorders.