Showing papers on "Cognitive decline published in 2006"
McGill University1, New York University2, Mayo Clinic3, French Institute of Health and Medical Research4, Federal Institute for Drugs and Medical Devices5, University of New South Wales6, Rush University Medical Center7, University of California, Los Angeles8, Vancouver Hospital and Health Sciences Centre9, University of Pittsburgh10, Ludwig Maximilian University of Munich11, VU University Medical Center12, Women's College, Kolkata13, Case Western Reserve University14, Karolinska Institutet15
TL;DR: Mild cognitive impairment can be regarded as a risk state for dementia, and its identification could lead to secondary prevention by controlling risk factors such as systolic hypertension.
3,962 citations
TL;DR: This review of the extant literature on age-related differences and changes in brain structure, including postmortem and noninvasive magnetic resonance imaging (MRI) studies, surveys the evidence from volumetry, diffusion-tensor imaging, and evaluations of white matter hyperintensities and speculate on several proposed mechanisms of differential brain aging.
1,085 citations
TL;DR: This study supports the concept that synapse loss is an early event in the disease process and suggests that MCI may be a transition stage between eAD and NCI with synaptic loss a structural correlate involved in cognitive decline.
883 citations
TL;DR: Administration of omega-3 fatty acid in patients with mild to moderate AD did not delay the rate of cognitive decline according to the MMSE or the cognitive portion of the Alzheimer Disease Assessment Scale, and positive effects were observed in a small group of patients with very mild AD.
Abstract: Background: Epidemiologic and animal studies have suggested that dietary fish or fish oil rich in-3 fatty acids, for example, docosahexaenoic acid and eicosapentaenoic acid, may prevent Alzheimer disease (AD). Objective: To determine effects of dietary-3 fatty acid supplementation on cognitive functions in patients with mild to moderate AD. Design: Randomized, double-blind, placebo-controlled clinical trial. Participants: Two hundred four patients with AD (age range [mean±SD], 74±9 years) whose conditions were stable while receiving acetylcholine esterase inhibitor treatment and who had a Mini-Mental State Examination (MMSE) score of 15 points or more were randomized to daily intake of 1.7 g of docosahexaenoic acid and 0.6 g of eicosapentaenoic acid (-3 fatty acid–treated group) or placebo for 6 months, after which all received-3 fatty acid supplementation for 6 months more. Main Outcome Measures: The primary outcome was cognition measured with the MMSE and the cognitive portion of the Alzheimer Disease Assessment Scale. The secondary outcome was global function as assessed with the Clinical Dementia Rating Scale; safety and tolerability of -3 fatty acid supplementation; and blood pressure determinations. Results: One hundred seventy-four patients fulfilled the trial. At baseline, mean values for the Clinical Dementia Rating Scale, MMSE, and cognitive portion of the Alzheimer Disease Assessment Scale in the 2 randomized groups were similar. At 6 months, the decline in cognitive functions as assessed by the latter 2 scales did not differ between the groups. However, in a subgroup (n=32) with very mild cognitive dysfunction (MMSE 27 points), a significant (P.05) reduction in MMSE decline rate was observed in the-3 fatty acid–treated group compared with the placebo group. A similar arrest in decline rate was observed between 6 and 12 months in this placebo subgroup when receiving-3 fatty acid supplementation. The -3 fatty acid treatment was safe and well tolerated. Conclusions: Administration of -3 fatty acid in patients with mild to moderate AD did not delay the rate of cognitive decline according to the MMSE or the cognitive portion of the Alzheimer Disease Assessment Scale. However, positive effects were observed in a small group of patients with very mild AD (MMSE 27 points). Trial Registration: clinicaltrials.gov Identifier: NCT00211159
695 citations
TL;DR: It is demonstrated that intensive, plasticity-engaging training can result in an enhancement of cognitive function in normal mature adults.
Abstract: Normal aging is associated with progressive functional losses in perception, cognition, and memory. Although the root causes of age-related cognitive decline are incompletely understood, psychophysical and neuropsychological evidence suggests that a significant contribution stems from poorer signal-to-noise conditions and down-regulated neuromodulatory system function in older brains. Because the brain retains a lifelong capacity for plasticity and adaptive reorganization, dimensions of negative reorganization should be at least partially reversible through the use of an appropriately designed training program. We report here results from such a training program targeting age-related cognitive decline. Data from a randomized, controlled trial using standardized measures of neuropsychological function as outcomes are presented. Significant improvements in assessments directly related to the training tasks and significant generalization of improvements to nonrelated standardized neuropsychological measures of memory (effect size of 0.25) were documented in the group using the training program. Memory enhancement appeared to be sustained after a 3-month no-contact follow-up period. Matched active control and no-contact control groups showed no significant change in memory function after training or at the 3-month follow-up. This study demonstrates that intensive, plasticity-engaging training can result in an enhancement of cognitive function in normal mature adults.
654 citations
TL;DR: Three white matter-mediated neural system hypotheses of aging brain structure and function are proposed: the anteroposterior gradient, bilateral recruitment of brain systems via the corpus callosum for frontally based task execution, and frontocerebellar synergism.
624 citations
TL;DR: It is reported that stress-level glucocorticoid administration increases Aβ formation by increasing steady-state levels of amyloid precursor protein (APP) and β-APP cleaving enzyme and augments tau accumulation, indicating that this hormone also accelerates the development of neurofibrillary tangles.
Abstract: Various environmental and genetic factors influence the onset and progression of Alzheimer’s disease (AD). Dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, which controls circulating levels of glucocorticoid hormones, occurs early in AD, resulting in increased cortisol levels. Disturbances of the HPA axis have been associated with memory impairments and may contribute to the cognitive decline that occurs in AD, although it is unknown whether such effects involve modulation of the amyloid β-peptide (Aβ) and tau. Using in vitro and in vivo experiments, we report that stress-level glucocorticoid administration increases Aβ formation by increasing steady-state levels of amyloid precursor protein (APP) and β-APP cleaving enzyme. Additionally, glucocorticoids augment tau accumulation, indicating that this hormone also accelerates the development of neurofibrillary tangles. These findings suggest that high levels of glucocorticoids, found in AD, are not merely a consequence of the disease process but rather play a central role in the development and progression of AD.
552 citations
TL;DR: In this article, the authors integrate seminal findings from cognitive research across lifespans of individuals, and also neuropsychological and neurobiological findings, to identify key questions and some potential answers, and to set challenges for fostering future research into intra-individual variability.
549 citations
TL;DR: The utility of SMCs in the diagnosis of pre-dementia states (e.g. mild cognitive impairment) is uncertain and requires further evaluation.
Abstract: Subjective memory complaints (SMCs) are common in older people and are often thought to indicate cognitive impairment. We reviewed research on the relationship between SMCs and (a) current cognitive function, (b) risk of future cognitive decline, and (c) depression and personality. SMCs were found to be inconsistently related to current cognitive impairment but were more strongly related to risk of future cognitive decline. However, SMCs were consistently related to depression and some personality traits, e.g. neuroticism. In conclusion, the determinants of SMCs are complex. The utility of SMCs in the diagnosis of pre-dementia states (e.g. mild cognitive impairment) is uncertain and requires further evaluation.
547 citations
TL;DR: There are consistent, albeit moderate, correlations between the progression of cognitive impairment and increasing brain lesion load and brain atrophy in MS, and among clinical predictors, incipient cognitive decline seems to be the major risk factor for further deterioration in the short-term.
488 citations
TL;DR: Cross-sectionally, a higher BMI was associated with lower cognitive scores after adjustment for age, sex, educational level, blood pressure, diabetes, and other psychosocial covariables, and this association was significant for word-list learning.
Abstract: Objective: To assess whether body mass index (BMI) is associated with cognitive function and cognitive decline in healthy men and women. Methods: In this prospective cohort study, we analyzed data from 2,223 healthy workers aged 32 to 62 years at baseline. Medical, psychosocial, and environmental data were collected in 1996 and in 2001. We tested cognitive functions at baseline and at follow-up with word-list learning (four recalls), a Digit–Symbol Substitution Test, and a selective attention test. Results: Cross-sectionally, a higher BMI was associated with lower cognitive scores after adjustment for age, sex, educational level, blood pressure, diabetes, and other psychosocial covariables. A higher BMI at baseline was also associated with a higher cognitive decline at follow-up, after adjustment for the above-cited confounding factors. This association was significant for word-list learning. For the changes in scores at word-list learning (delayed recall), regression coefficients were −0.008 ± 0.13, −0.09 ± 0.13, −0.17 ± 0.14, and −0.35 ± 0.14 ( p for trend Conclusions: Body mass index was independently associated both with cognitive function (word-list learning and Digit–Symbol Substitution Test) and changes in word-list learning in healthy, nondemented, middle-aged men and women.
TL;DR: A brain-plasticity-based intervention targeting normal age-related cognitive decline may potentially offer benefit to a broad population of older adults and be applicable to all aging adults with the promise of improving their operational capabilities.
Abstract: 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 loss in brain function driven by aging brain machinery, or more likely from both. In aggregate, these interrelated factors promote plastic changes in the brain that result in age-related functional decline. This new viewpoint on the root causes of functional decline immediately suggests a remedial approach. Studies of adult brain plasticity have shown that substantial improvement in function and/or recovery from losses in sensation, cognition, memory, motor control, and affect should be possible, using appropriately designed behavioral training paradigms. Driving brain plasticity with positive outcomes requires engaging older adults in demanding sensory, cognitive, and motor activities on an intensive basis, in a behavioral context designed to re-engage and strengthen the neuromodulatory systems that control learning in adults, with the goal of increasing the fidelity, reliability, and power of cortical representations. Such a training program would serve a substantial unmet need in aging adults. Current treatments directed at age-related functional losses are limited in important ways. Pharmacological therapies can target only a limited number of the many changes believed to underlie functional decline. Behavioral approaches focus on teaching specific strategies to aid higher order cognitive functions, and do not usually aspire to fundamentally change brain function. A brain-plasticity-based training program would potentially be applicable to all aging adults with the promise of improving their operational capabilities. We have constructed such a brain-plasticity-based training program and conducted an initial randomized controlled pilot study to evaluate the feasibility of its use by older adults. A main objective of this initial study was to estimate the effect size on standardized neuropsychological measures of memory. We found that older adults could learn the training program quickly, and could use it entirely unsupervised for the majority of the time required. Pre- and posttesting documented a significant improvement in memory within the training group (effect size 0.41, p<0.0005), with no significant within-group changes in a time-matched computer using active control group, or in a no-contact control group. Thus, a brain-plasticity-based intervention targeting normal age-related cognitive decline may potentially offer benefit to a broad population of older adults.
TL;DR: In this article, the authors evaluated the effectiveness of community-based occupational therapy on daily functioning of patients with dementia and the sense of competence of their care givers, and found that 10 sessions of occupational therapy over five weeks, including cognitive and behavioural interventions, to train patients in the use of aids to compensate for cognitive decline, reduced the burden on the care giver, despite the patients limited learning ability.
Abstract: Objective To determine the effectiveness of community based occupational therapy on daily functioning of patients with dementia and the sense of competence of their care givers. Design Single blind randomised controlled trial. Assessors were blinded for treatment allocation. Setting Memory clinic and day clinic of a geriatrics department and participants’ homes. Participants 135 patients aged ≥ 65 with mild to moderate dementia living in the community and their primary care givers. Interventions 10 sessions of occupational therapy over five weeks, including cognitive and behavioural interventions, to train patients in the use of aids to compensate for cognitive decline and care givers in coping behaviours and supervision. Main outcome measures Patients’ daily functioning assessed with the assessment of motor and process skills (AMPS) and the performance scale of the interview of deterioration in daily activities in dementia (IDDD). Care giver burden assessed with the sense of competence questionnaire (SCQ). Participants were evaluated at baseline, six weeks, and three months. Results Scores improved significantly relative to baseline in patients and care givers in the intervention group compared with the controls (differences were 1.5 (95% confidence interval 1.3 to 1.7) for the process scale; − 11.7 ( − 13.6 to − 9.7) for the performance scale; and (11.0; 9.2 to 12.8) for the competence scale). This improvement was still significant at three months. The number needed to treat to reach a clinically relevant improvement in motor and process skills score was 1.3 (1.2 to 1.4) at six weeks. Effect sizes were 2.5, 2.3, and 1.2, respectively, at six weeks and 2.7, 2.4, and 0.8, respectively, at 12 weeks. Conclusions Occupational therapy improved patients’ daily functioning and reduced the burden on the care giver, despite the patients’ limited learning ability. Effects were still present at 12 weeks, which justifies implementation of this intervention.
TL;DR: In this paper, structural and diffusion tensor imaging (DTI) revealed a heterogeneous set of differences associated with cognitive decline in aging, and suggested that increased activation is either caused by structural disruption or is a compensatory response to such disruption.
Abstract: To explore neural correlates of cognitive decline in aging, we used longitudinal behavioral data to identify two groups of older adults (n = 40) that differed with regard to whether their performance on tests of episodic memory remained stable or declined over a decade. Analysis of structural and diffusion tensor imaging (DTI) revealed a heterogeneous set of differences associated with cognitive decline. Manual tracing of hippocampal volume showed significant reduction in those older adults with a declining memory performance as did DTI-measured fractional anisotropy in the anterior corpus callosum. Functional magnetic resonance imaging during incidental episodic encoding revealed increased activation in left prefrontal cortex for both groups and additional right prefrontal activation for the elderly subjects with the greatest decline in memory performance. Moreover, mean DTI measures in the anterior corpus callosum correlated negatively with activation in right prefrontal cortex. These results demonstrate that cognitive decline is associated with differences in the structure as well as function of the aging brain, and suggest that increased activation is either caused by structural disruption or is a compensatory response to such disruption.
TL;DR: In a substantial proportion of PD patients who develop postural instability and gait disorder during the course of the disease, this transition is associated with accelerated cognitive decline and highly increased risk for subsequent dementia, raising the question whether PIGD and dementia share common or parallel neuropathology.
Abstract: The objective of this study was to assess the temporal relationship between changes in predominant motor symptoms and incident dementia in Parkinson's disease (PD). A community-based sample of 171 nondemented patients with PD was followed prospectively and examined at baseline and after 4 and 8 years. The motor subtype of Parkinsonism was classified into tremor-dominant (TD), indeterminate, or postural instability gait difficulty (PIGD) subtype at each visit, based on defined items in the Unified Parkinson's Disease Rating Scale, subscales II and III. Dementia was diagnosed according to DSM-III-R criteria, based on clinical interview, cognitive rating scales, and neuropsychological examination. Logistic regression was used to analyze the relationship between subtype of Parkinsonism and dementia. Transition from TD to PIGD subtype was associated with a more than threefold increase in the rate of Mini-Mental State Examination decline. Compared to patients with persistent TD or indeterminate subtype, the odds ratio for dementia was 56.7 (95% CI: 4.0–808.4; P = 0.003) for patients changing from TD or indeterminate subtype to PIGD subtype, and 80.0 (95% CI: 4.6–1400.1; P = 0.003) for patients with persistent PIGD subtype. Patients with TD subtype at baseline did not become demented until they developed PIGD subtype, and dementia did not occur among patients with persistent TD subtype of Parkinsonism. In a substantial proportion of PD patients who develop postural instability and gait disorder during the course of the disease, this transition is associated with accelerated cognitive decline and highly increased risk for subsequent dementia. These findings raise the question whether PIGD and dementia share common or parallel neuropathology. © 2006 Movement Disorder Society
01 Jan 2006
TL;DR: It is demonstrated that cognitive decline is associated with differences in the structure as well as function of the aging brain, and suggested that increased activation is either caused by structural disruption or is a compensatory response to such disruption.
Abstract: To explore neural correlates of cognitive decline in aging, we used longitudinal behavioral data to identify two groups of older adults (n 5 40) that differed with regard to whether their performance on tests of episodic memory remained stable or declined over a decade. Analysis of structural and diffusion tensor imaging (DTI) revealed a heterogeneous set of differences associated with cognitive decline. Manual tracing of hippocampal volume showed significant reduction in those older adults with a declining memory performance as did DTI-measured fractional anisotropy in the anterior corpus callosum. Functional magnetic resonance imaging during incidental episodic encoding revealed increased activation in left prefrontal cortex for both groups and additional right prefrontal activation for the elderly subjects with the greatest decline in memory performance. Moreover, mean DTI measures in the anterior corpus callosum correlated negatively with activation in right prefrontal cortex. These results demonstrate that cognitive decline is associated with differences in the structure as well as function of the aging brain, and suggest that increased activation is either caused by structural disruption or is a compensatory response to such disruption.
TL;DR: A PIGD motor subtype is associated with a faster rate of cognitive decline in PD and may be considered a risk factor for incident dementia in PD.
Abstract: Background: A previous cross sectional study found over-representation of a postural instability gait difficulty (PIGD) motor subtype in Parkinson’s disease patients with dementia (PDD) and dementia with Lewy bodies (DLB), compared with Parkinson’s disease (PD). Aims: (1) To examine rates of cognitive and motor decline over two years in PD (n = 40), PDD (n = 42) and DLB (n = 41) subjects, compared with age matched controls (n = 41), (2) to record whether motor phenotypes of PD, PDD, and DLB subjects changed during the study, (3) to find out if cognitive and motor decline in PD was associated with baseline motor subtype, and (4) to report the incidence of dementia in PD patients in relation to baseline motor subtype. Results: Most of PDD and DLB participants were PIGD subtype at baseline assessment. In the non-demented PD group, tremor dominant (TD) and PIGD subtypes were more evenly represented. Cognitive decline over two years was greater in PDD and DLB groups (mean decline in MMSE − 4.5 and − 3.9, respectively), compared with PD ( − 0.2) and controls (−0.3). There was an association between PIGD subtype and increased rate of cognitive decline within the PD group. Of 40 PD patients, 25% of the 16 PIGD subtype developed dementia over two years, compared with none of the 18 TD or six indeterminate phenotype cases (χ 2 = 6.7, Fisher’s exact test p Conclusion: A PIGD motor subtype is associated with a faster rate of cognitive decline in PD and may be considered a risk factor for incident dementia in PD.
TL;DR: The results are consistent with white matter damage due to axonal loss, causing age- related cognitive decline, and working memory may be particularly dependent on complex networks dependent on white matter connections.
Abstract: Background: Damage to white matter tracts, resulting in “cerebral disconnection,” may underlie age-related cognitive decline. Methods: Using diffusion tensor MRI (DTI) to investigate white matter damage, and magnetic resonance spectroscopy (MRS) to look at its underlying pathologic basis, the authors investigated the relationship between white matter structure and cognition in 106 healthy middle-aged and elderly adults. Fractional anisotropy (FA) and mean diffusivity (MD) values, whole brain white matter histograms, and regions of interest placed in the white matter of the centrum semiovale were analyzed. Correlations with executive function, working memory, and information-processing speed were performed. Results: There was a progressive reduction in FA and increase in diffusivity with age in both region of interest (r = 0.551, p r = 0.625, p N -acetyl aspartate, a neuronal marker, with DTI parameters ( r = 0.253, p Conclusion: The results are consistent with white matter damage due to axonal loss, causing age- related cognitive decline. Working memory may be particularly dependent on complex networks dependent on white matter connections.
TL;DR: Testing the hypothesis that neuritic plaques and neurofibrillary tangles are more pronounced in the hippocampus of patients with AD with a lifetime history of major depressive disorder found it to be true, suggesting an interaction between major depression and AD neuropathology.
Abstract: Context The hallmark pathological changes in Alzheimer disease (AD) are abundant plaque and tangle formation, especially in the temporal lobes and hippocampus. Although there is increasing evidence that major depression may interact with neuropathological processes in AD, there have been no studies of neuropathological changes in AD as a function of history of major depression. Objective To test the hypothesis that neuritic plaques and neurofibrillary tangles are more pronounced in the hippocampus of patients with AD with a lifetime history of major depressive disorder, as compared with patients with AD without depression history. Design Postmortem study. Setting Nursing home. Participants The brains of 52 patients with AD without a lifetime history of major depression were compared with the brains of 50 patients with AD with a lifetime history of major depression. Main Outcome Measures Neuropathological ratings from the Consortium to Establish a Registry in Alzheimer Disease battery. Results Brains of patients with AD with a lifetime history of depression showed higher levels of both plaque (P Conclusions In AD, the presence of a lifetime history of depression corresponds to increases in AD-related neuropathological changes within the hippocampus. These changes go along with more rapid cognitive decline in patients with AD with a history of depression, and are more pronounced in patients with AD suffering from depression early on in the disease process, suggesting an interaction between major depression and AD neuropathology.
TL;DR: The essential fatty acids, particularly the n-3 long-chain polyunsaturated fatty acids (LCPs), are important for brain development during both the fetal and postnatal period and are also increasingly seen to be of value in limiting the cognitive decline during aging.
Abstract: The essential fatty acids (EFAs), particularly the n-3 long-chain polyunsaturated fatty acids (LCPs), are important for brain development during both the fetal and postnatal period. They are also increasingly seen to be of value in limiting the cognitive decline during aging. EFA deficiency was first shown over 75 years ago, but the more subtle effects of the n-3 fatty acids in terms of skin changes, a poor response to linoleic acid supplementation, abnormal visual function, and peripheral neuropathy were only discovered later. Both n-3 and n-6 LCPs play important roles in neuronal growth, development of synaptic processing of neural cell interaction, and expression of genes regulating cell differentiation and growth. The fetus and placenta are dependent on maternal EFA supply for their growth and development, with docosahexaenomic acid (DHA)-supplemented infants showing significantly greater mental and psychomotor development scores (breast-fed children do even better). Dietary DHA is needed for the optimum functional maturation of the retina and visual cortex, with visual acuity and mental development seemingly improved by extra DHA. Aging is also associated with decreased brain levels of DHA: fish consumption is associated with decreased risk of dementia and Alzheimer's disease, and the reported daily use of fish-oil supplements has been linked to improved cognitive function scores, but confirmation of these effects is needed.
TL;DR: It is suggested that dendritic-like microglia, by facilitating the necessary adjustment, might contribute significantly to the brain's resistance to AD and argue against the use of antiinflammatory drugs.
Abstract: Alzheimer’s disease (AD) is characterized by plaque formation, neuronal loss, and cognitive decline. The functions of the local and systemic immune response in this disease are still controversial. Using AD double-transgenic (APP/PS1) mice, we show that a T cell-based vaccination with glatiramer acetate, given according to a specific regimen, resulted in decreased plaque formation and induction of neurogenesis. It also reduced cognitive decline, assessed by performance in a Morris water maze. The vaccination apparently exerted its effect by causing a phenotype switch in brain microglia to dendritic-like (CD11c) cells producing insulin-like growth factor 1. In vitro findings showed that microglia activated by aggregated β-amyloid, and characterized as CD11b+/CD11c−/MHC class II−/TNF-α+ cells, impeded neurogenesis from adult neural stem/progenitor cells, whereas CD11b+/CD11c+/MHC class II+/TNF-α− microglia, a phenotype induced by IL-4, counteracted the adverse β-amyloid-induced effect. These results suggest that dendritic-like microglia, by facilitating the necessary adjustment, might contribute significantly to the brain’s resistance to AD and argue against the use of antiinflammatory drugs.
TL;DR: High vegetable but not fruit consumption may be associated with slower rate of cognitive decline with older age, and the association remained significant with further control of cardiovascular-related conditions and risk factors.
Abstract: Objective: To examine the association between rates of cognitive change and dietary consumption of fruits and vegetables among older persons Methods: The authors conducted a prospective cohort study of 3,718 participants, aged 65 years and older of the Chicago Health and Aging Project Participants completed a food frequency questionnaire and were administered at least two of three cognitive assessments at baseline, 3-year, and 6-year follow-ups Cognitive function was measured using the average z-score of four tests: the East Boston Tests of immediate memory and delayed recall, the Mini-Mental State Examination, and the Symbol Digit Modalities Test Results: The mean cognitive score at baseline for the analyzed cohort was 018 (range: –35 to 16), and the overall mean change in score per year was a decline of 004 standardized units In mixed effects models adjusted for age, sex, race, and education, compared with the rate of cognitive decline among persons in the lowest quintile of vegetable intake (median of 09 servings/day), the rate for persons in the fourth quintile (median, 28 servings/day) was slower by 0019 standardized units per year ( p = 001), a 40% decrease, and by 0018 standardized units per year ( p = 002) for the fifth quintile (median, 41 servings/day), or a 38% decrease in rates The association remained significant ( p for linear trend = 002) with further control of cardiovascular-related conditions and risk factors Fruit consumption was not associated with cognitive change Conclusion: High vegetable but not fruit consumption may be associated with slower rate of cognitive decline with older age
TL;DR: 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 in the older adult.
Abstract: 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.
TL;DR: This study affirms that the link between behavioural brain reserve and incident dementia is most likely due to fundamentally different cognitive trajectories rather than confound factors.
Abstract: Background. A previous companion paper to this report (Valenzuela & Sachdev, Psychological Medicine 2006, 36, 441–454) suggests a link between behavioural brain reserve and incident dementia; however, the issues of covariate control and ascertainment bias were not directly addressed. Our aim was to quantitatively review an independent set of longitudinal studies of cognitive change in order to clarify these factors.Method. Cohort studies of the effects of education, occupation, and mental activities on cognitive decline were of interest. Abstracts were identified in MEDLINE (1966–September 2004), CURRENT CONTENTS (to September 2004), PsychINFO (1984–September 2004), Cochrane Library Databases and reference lists from relevant articles. Eighteen studies met inclusion criteria. Key information was extracted by both reviewers onto a standard template with a high level of agreement. Cognitive decline studies were integrated using a non-parametric method after converting outcome data onto a common effect size metric.Results. Higher behavioural brain reserve was related to decreased longitudinal cognitive decline after control for covariates in source studies (ϕ=1·70, p<0·001). This effect was robust to correction for both multiple predictors and multiple outcome measures and was the result of integrating data derived from more than 47000 individuals.Conclusions. This study affirms that the link between behavioural brain reserve and incident dementia is most likely due to fundamentally different cognitive trajectories rather than confound factors.
TL;DR: A novel monoclonal antibody, NAB61, is generated that preferentially recognizes a conformational epitope present in dimeric, small oligomeric, and higher order Aβ structures but not full-length amyloid-β precursor protein or C-terminal amyloidal precursor protein fragments.
TL;DR: Depressive symptoms are cross-sectionally associated with cognitive impairment but not subsequent cognitive decline, and substantial cognitive decline over time cannot be explained by depression and most likely reflects incipient dementia.
Abstract: Context: Depression is associated with cognitive impairment and dementia. It is less clear whether depression contributes to further cognitive decline over time, independently of incipient dementia. Objective: To examine the relationship between depressive symptoms and subsequent cognitive decline in a cohort of nondemented older adults, some of whom remained dementia free during follow-up and others in whom incident dementia eventually developed. Design: Twelve-year prospective epidemiological study, including biennial measurement of cognition and depressive symptoms, biennial assessment of dementia, and comparison of cognitive function at baseline and over time in persons with and without baseline depressive symptoms in the dementia-free and eventual-dementia groups, using random-effects models. Setting: A largely blue-collar rural community. Participants: Population-based sample of 1265 adults 67 years and older without dementia at baseline. Main Outcome Measures: Scores over time on each of several cognitive test composites. Results: Among 1094 participants who remained dementia free, those with baseline depressive symptoms had significantly lower baseline scores on all cognitive composites than the nondepressed participants. Among the 171 individuals in whom dementia later developed, depression was associated with worse performance in some but not all baseline cognitive composites. Cognitive decline over time was minimal in the dementia-free group, whereas marked decline was seen in the eventualdementia group. Depressive symptoms were not associated with rate of cognitive decline over time in either group.
TL;DR: The current evidence has not shown a significant difference in postoperative delirium or cognitive decline among other more frequently used postoperative opioids such as morphine, fentanyl, or hydromorphone, and available studies suggest that IV or epidural techniques do not influence cognitive function differently.
Abstract: Postoperative delirium and cognitive decline are adverse events that occur frequently in elderly patients. Preexisting patient factors, medications, and various intraoperative and postoperative causes have been implicated in the development of postoperative delirium and cognitive decline. Despite previous studies identifying postoperative pain as a risk factor, relatively few clinical studies have compared the effect of common postoperative pain management techniques (IV and epidural) or opioid analgesics on postoperative cognitive status. A systematic search of the PubMed and CINAHL databases identified six studies comparing different opioid analgesics on postoperative delirium and cognitive decline and five studies comparing IV and epidural routes of administering analgesia. Meperidine was consistently associated with an increased risk of delirium in elderly surgical patients, but the current evidence has not shown a significant difference in postoperative delirium or cognitive decline among other more frequently used postoperative opioids such as morphine, fentanyl, or hydromorphone. The available studies also suggest that IV or epidural techniques do not influence cognitive function differently. However, future investigations of sufficient study size and more standardized methods of defining outcomes are necessary to confirm the current findings.
TL;DR: BDNF serum values are increased in early stages of Alzheimer’s disease, which may reflect a compensatory repair mechanism in early neurodegeneration and could also contribute to increased degradation of beta-amyloid (Abeta).
Abstract: Alzheimer’s disease (AD) is characterized by cognitive decline and loss of neurons in specific brain regions. Recent findings have suggested an involvement of brain-derived neurotrophic factor (BDNF) in the pathogenesis of AD. BDNF is an endogenous protein involved in the maintenance of neuronal function, synaptic plasticity and structural integrity in the adult brain.
TL;DR: Some cytotoxic treatment for breast cancer affects cognition in a subset of women, and changes in cognitive performance among high-risk breast cancer patients who had received high-dose chemotherapy with cyclophosphamide, thiotepa, and carboplatin are examined.
Abstract: Some breast cancer survivors experience cognitive decline following chemotherapy We prospectively examined changes in cognitive performance among high-risk breast cancer patients who had received high-dose chemotherapy with cyclophosphamide, thiotepa, and carboplatin (CTC group; n = 28) or standard-dose chemotherapy with 5-fluorouracil, epirubicin, and cyclophosphamide (FEC group; n = 39); stage-I breast cancer patients who had received no systemic chemotherapy (no-CT group; n = 57); and healthy control subjects (n = 60) All patients underwent neuropsychologic testing before and 6 months after treatment (12-month interval); control subjects underwent repeated testing over a 6-month interval No differences in cognitive functioning between the four groups were observed at the first assessment More of the CTC group than the control subjects experienced a deterioration in cognitive performance over time (25% versus 67%; odds ratio [OR] = 53, 95% confidence interval [CI] = 13 to 212, P = 02) No such difference was observed for the FEC or the no-CT groups (FEC versus control: OR = 22, 95% CI = 05 to 91, P = 27; no-CT versus Control: OR = 22, 95% CI = 06 to 80; P = 21) Some cytotoxic treatment for breast cancer affects cognition in a subset of women
TL;DR: The substantial overlap in risk factors points to new avenues for research and prevention of dementia, including hypertension, high LDL cholesterol, low HDL cholesterol and especially diabetes, which appears to be protective for both CVD and dementia.
Abstract: Growing evidence supports a strong and likely causal association between cardiovascular disease (CVD), and its risk factors, with incidence of cognitive decline and Alzheimer's disease. Individuals with subclinical CVD are at higher risk for dementia and Alzheimer's. Several cardiovascular risk factors are also risk factors for dementia, including hypertension, high LDL cholesterol, low HDL cholesterol and especially diabetes. Moderate alcohol appears to be protective for both CVD and dementia. In contrast, inflammatory markers predict cardiovascular risk, but not dementia, despite biological plausibility for such a link. The substantial overlap in risk factors points to new avenues for research and prevention.