Showing papers on "Cognitive decline published in 2002"
TL;DR: It is shown that the deficit in neurogenesis reflects alterations in the microenvironment that regulates progenitor-cell fate, as well as a defect in the proliferative capacity of the neural progenitors in the irradiated hippocampus.
Abstract: In both pediatric and adult patients, cranial radiation therapy causes a debilitating cognitive decline that is poorly understood and currently untreatable. This decline is characterized by hippocampal dysfunction, and seems to involve a radiation-induced decrease in postnatal hippocampal neurogenesis. Here we show that the deficit in neurogenesis reflects alterations in the microenvironment that regulates progenitor-cell fate, as well as a defect in the proliferative capacity of the neural progenitor-cell population. Not only is hippocampal neurogenesis ablated, but the remaining neural precursors adopt glial fates and transplants of non-irradiated neural precursor cells fail to differentiate into neurons in the irradiated hippocampus. The inhibition of neurogenesis is accompanied by marked alterations in the neurogenic microenvironment, including disruption of the microvascular angiogenesis associated with adult neurogenesis and a marked increase in the number and activation status of microglia within the neurogenic zone. These findings provide clear targets for future therapeutic interventions.
1,186 citations
Book•
25 Apr 2002
TL;DR: Findings from 5 large, randomized studies of the symptomatic treatment of probable and possible vascular dementia indicate that the presence of a cholinergic deficit is not required for the anticholinesterases to produce cognitive improvement, and so the cholin allergic hypothesis is neither necessary nor sufficient to explain the effects of these drugs.
Abstract: Cerebrovascular disease is the second most common cause of acquired cognitive impairment and dementia and contributes to cognitive decline in the neurodegenerative dementias. The current narrow definitions of vascular dementia should be broadened to recognise the important part cerebrovascular disease plays in several cognitive disorders, including the hereditary vascular dementias, multi-infarct dementia, post-stroke dementia, subcortical ischaemic vascular disease and dementia, mild cognitive impairment, and degenerative dementias (including Alzheimer's disease, frontotemporal dementia, and dementia with Lewy bodies). Here we review the current state of scientific knowledge on the subject of vascular brain burden. Important non-cognitive features include depression, apathy, and psychosis. We propose use of the term vascular cognitive impairment, which is characterised by a specific cognitive profile involving preserved memory with impairments in attentional and executive functioning. Diagnostic criteria have been proposed for some subtypes of vascular cognitive impairment, and there is a pressing need to validate and further refine these. Clinical trials in vascular cognitive impairment are in their infancy but support the value of therapeutic interventions for symptomatic treatment.
1,148 citations
01 Jan 2002
TL;DR: A number of theories and frameworks have emerged that try to address both the potentials and limitations of effective cognitive and social functioning during the adult years (e.g., Baltes et al. as discussed by the authors ).
Abstract: In recent years, a number of theories and frameworks have emerged that try to address both the potentials and limitations of effective cognitive and social functioning during the adult years (e.g., Baltes & Staudinger, 2000; Baltes, Staudinger, & Lindenberger, 1999; Hoyer & Rybash, 1994; Lemme, 1999; Rowe & Kahn, 1997; Seligman & Csikszentmihalyi, 2000; Staudinger & Pasupathi, 2000; Wapner & Demick, this volume). Such frameworks have aided the articulation of the characteristics of adult development by integrating observations that would otherwise have been disconnected pieces of a puzzle and less meaningful. In the study of adult cognitive development, for example, much of the available data and theory address the description and explanation of age-related cognitive decline. However, everyday observations and the results from some studies suggest that there are improvements or stability as well as declines in cognitive function during the adult years. The aim of the present chapter is to describe what is known about the potentials as well as limits of learning during the adult years.
1,006 citations
TL;DR: Observations suggest that CBS activity is reduced in AD brains and the decrease in H2S may be involved in some aspects of the cognitive decline in AD.
734 citations
TL;DR: Two separate forms of age-associated change in frontal cortex are suggested: under-recruitment and nonselective recruitment; the former is reversible and potentially amenable to cognitive training; the latter may reflect a less malleable change associated with cognitive decline in advanced aging.
712 citations
TL;DR: Cognitive deficits in MCI and early AD are not associated with the loss of ChAT and occur despite regionally specific upregulation, suggesting that the earliest cognitive deficits in AD involve brain changes other than simply cholinergic system loss.
Abstract: In Alzheimer's disease (AD), loss of cortical and hippocampal choline acetyltransferase (ChAT) activity has been correlated with dementia severity and disease duration, and it forms the basis for current therapies. However, the extent to which reductions in ChAT activity are associated with early cognitive decline has not been well established. We quantified ChAT activity in the hippocampus and four cortical regions (superior frontal, inferior parietal, superior temporal, and anterior cingulate) of 58 individuals diagnosed with no cognitive impairment (NCI; n = 26; mean age 81.4 ± 7.3 years), mild cognitive impairment (MCI; n = 18; mean age 84.5 ± 5.7), or mild AD (n =14; mean age 86.3 ± 6.6). Inferior parietal cortex ChAT activity was also assessed in 12 subjects with end-stage AD (mean age 81.4 ± 4.3 years) and compared to inferior parietal cortex ChAT levels of the other three groups. Only the end-stage AD group had ChAT levels reduced below normal. In individuals with MCI and mild AD, ChAT activity was unchanged in the inferior parietal, superior temporal, and anterior cingulate cortices compared to NCI. In contrast, ChAT activity in the superior frontal cortex was significantly elevated above normal controls in MCI subjects, whereas the mild AD group was not different from NCI or MCI. Hippocampal ChAT activity was significantly higher in MCI subjects than in either NCI or AD. Our results suggest that cognitive deficits in MCI and early AD are not associated with the loss of ChAT and occur despite regionally specific upregulation. Thus, the earliest cognitive deficits in AD involve brain changes other than simply cholinergic system loss. Of importance, the cholinergic system is capable of compensatory responses during the early stage of dementia. The upregulation in frontal cortex and hippocampal ChAT activity could be an important factor in preventing the transition of MCI subjects to AD.
643 citations
TL;DR: Small infarcts in AD patients have no essential impact on global cognitive decline which mainly depends on the severity of Alzheimer pathology, but in early stage of AD they may influence and promote the development of dementia.
Abstract: Recent epidemiological and clinico-pathologic data suggest overlaps between Alzheimer disease (AD) and cerebrovascular lesions that may magnify the effect of mild AD pathology and promote progression of cognitive decline or even may precede neuronal damage and dementia. Vascular pathology in the aging brain and in AD includes: 1. cerebral amyloid angiopathy (CAA) with an incidence of 82-98% often associated with ApoE epsilon 2 and causing a) cerebral mass hemorrhages (around 70%, mainly in the frontal and parietal lobes), b) multiple or recurrent microhemorrhages (15%), and c) ischemic (micro-)infarcts or lacunes (around 20%). The frequency of these lesions increases with the severity of CAA and shows no correlation with that of senile amyloid plaques. CAA, significantly more frequent in patients with cerebral hemorrhages or infarcts than in aged controls, is an important risk factor for cerebrovascular lesions in AD. 2. Microvascular changes with decreased density and structural abnormalities causing regional metabolic and blood-brain barrier dysfunctions with ensuing neuronal damage. In large autopsy series of demented aged subjects, around 80% show Alzheimer type pathology, 20-40% with additional, often minor vascular lesions, 7-10% "pure" vascular dementia, and 3-5% "mixed" dementia (combination of AD and vascular encephalopathy). AD cases with additional minor cerebrovascular lesions have significantly more frequent histories of hypertension or infarcts than "pure" AD patients. Vascular lesions in AD include cortical microinfarcts, subcortical lacunes, white matter lesions / leukoencephalopathy, small hemorrhages and corticosubcortical infarcts, while in mixed type dementia multiple larger or hemispheral infarcts are more frequent. Small infarcts in AD patients have no essential impact on global cognitive decline which mainly depends on the severity of Alzheimer pathology, but in early stage of AD they may influence and promote the development of dementia. Recent studies showed lower density of plaques and tangles in brains with cerebrovascular lesions, and similar severity of dementia was related to fewer AD lesions in brains with than in those without small vascular lesions. Further studies will help to elucidate the risk factors and impact of cerebrovascular lesions on the development and progression of dementia in AD.
620 citations
TL;DR: A relationship between elevated baseline plasma IL-6 and risk for subsequent decline in cognitive function is suggested, consistent with the hypothesized relationship between brain inflammation, as measured here by elevated plasmaIL-6, and neuropathologic disorders.
Abstract: Objective: To investigate whether plasma interleukin-6 (IL-6) is cross-sectionally related to poorer cognitive function and whether a baseline plasma IL-6 measurement can predict risk for decline in cognitive function in longitudinal follow-up of a population-based sample of nondisabled elderly people. Methods: A prospective cohort study of 779 high-functioning men and women aged 70 to 79 from the MacArthur Study of Successful Aging was conducted. Regression modeling was used to investigate whether baseline IL-6 levels (classified by tertiles) were associated with initial cognitive function and whether IL-6 levels predicted subsequent declines in cognitive function from 1988 to 1991 (2.5-year follow-up) and from 1988 to 1995 (7-year follow-up). Results: Subjects in the highest tertile for plasma IL-6 were marginally more likely to exhibit poorer baseline cognitive function (i.e., scores below the median), independent of demographic status, social status, health and health behaviors, and other physiologic variables (odds ratio [OR] = 1.46; 95% CI: 0.97, 2.20). At 2.5 years, those in both the second tertile of IL-6 (OR = 2.21; 95% CI: 1.44, 3.42) and the third tertile (OR = 2.03; 95% CI: 1.30, 3.19) were at increased risk of cognitive decline even after adjusting for all confounders. At 7 years of follow-up, only those in the highest IL-6 tertile were significantly more likely to exhibit declines in cognition (OR = 1.90; 95% CI: 1.14, 3.18) after adjustment for all confounders. Conclusions: The results suggest a relationship between elevated baseline plasma IL-6 and risk for subsequent decline in cognitive function. These findings are consistent with the hypothesized relationship between brain inflammation, as measured here by elevated plasma IL-6, and neuropathologic disorders.
498 citations
TL;DR: Patients who received their first CABG surgery without cardiopulmonary bypass had improved cognitive outcomes 3 months after the procedure, but the effects were limited and became negligible at 12 months.
Abstract: ContextCoronary artery bypass graft (CABG) surgery is associated with a decline
in cognitive function, which has largely been attributed to the use of cardiopulmonary
bypass (on-pump procedures) Cardiac stabilizers facilitate CABG surgery without
use of cardiopulmonary bypass (off-pump procedures) and should reduce the
cognitive decline associated with on-pump proceduresObjectiveTo compare the effect of CABG surgery with (on-pump) and without (off-pump)
cardiopulmonary bypass on cognitive outcomeDesign and SettingRandomized controlled trial conducted in the Netherlands of CABG surgery
patients enrolled from March 1998 through August 2000, with 3- and 12-month
follow-upParticipants and InterventionPatients scheduled for their first CABG surgery (mean age, 61 years;
n = 281) were randomly assigned to off-pump surgery (n = 142) or on-pump surgery
(n = 139)Main Outcome MeasuresCognitive outcome at 3 and 12 months, which was determined by psychologists
(blinded for randomization) who administered 10 neuropsychological tests before
and after surgery Quality of life, stroke rate, and all-cause mortality at
3 and 12 months were secondary outcome measuresResultsCognitive outcome could be determined at 3 months in 248 patients Cognitive
decline occurred in 21% in the off-pump group and 29% in the on-pump group
(relative risk [RR], 065; 95% confidence interval [CI], 036-116; P = 15) The overall standardized change score (ie, improvement
of cognitive performance) was 019 in the off-pump vs 013 in the on-pump
group (P = 03) At 12 months, cognitive decline
occurred in 308% in the off-pump group and 336% in the on-pump group (RR,
088; 95% CI, 052-149; P = 69) The overall standardized
change score was 019 in the off-pump vs 012 in the on-pump group (P = 09) No statistically significant differences were
observed between the on-pump and off-pump groups in quality of life, stroke
rate, or all-cause mortality at 3 and 12 monthsConclusionPatients who received their first CABG surgery without cardiopulmonary
bypass had improved cognitive outcomes 3 months after the procedure, but the
effects were limited and became negligible at 12 months
492 citations
TL;DR: It is now known that significant numbers of cortical neurons are not lost and other bases for the cognitive decline have been sought, and it is likely that nerve fiber loss also contributes to cognitive decline, because of the consequent decrease in connections between neurons.
Abstract: It was believed that the cause of the cognitive decline exhibited by human and non-human primates during normal aging was a loss of cortical neurons. It is now known that significant numbers of cortical neurons are not lost and other bases for the cognitive decline have been sought. One contributing factor may be changes in nerve fibers. With age some myelin sheaths exhibit degenerative changes, such as the formation of splits containing electron dense cytoplasm, and the formation on myelin balloons. It is suggested that such degenerative changes lead to cognitive decline because they cause changes in conduction velocity, resulting in a disruption of the normal timing in neuronal circuits. Yet as degeneration occurs, other changes, such as the formation of redundant myelin and increasing thickness suggest of sheaths, suggest some myelin formation is continuing during aging. Another indication of this is that oligodendrocytes increase in number with age. In addition to the myelin changes, stereological studies have shown a loss of nerve fibers from the white matter of the cerebral hemispheres of humans, while other studies have shown a loss of nerve fibers from the optic nerves and anterior commissure in monkeys. It is likely that such nerve fiber loss also contributes to cognitive decline, because of the consequent decrease in connections between neurons. Degeneration of myelin itself does not seem to result in microglial cells undertaking phagocytosis. These cells are probably only activated when large numbers of nerve fibers are lost, as can occur in the optic nerve.
482 citations
TL;DR: The results raise the possibility that depressive symptoms in older persons may be associated with risk of developing AD and rate of cognitive decline.
Abstract: Background : Cross-sectional and retrospective case-control studies suggest an association of depression symptoms with cognitive impairment and AD, but there have been few prospective studies and their results have been inconsistent. Methods : Participants are Catholic clergy members who were aged ≥65 years and who did not have clinical evidence of AD. During a 7-year period, they underwent annual clinical evaluations that included clinical classification of AD and detailed cognitive function testing from which global and specific measures of cognition were derived. Number of depressive symptoms was assessed at baseline with a modified, 10-item Center for Epidemiologic Studies Depression Scale (CES-D). The association of CES-D score with incident AD, using proportional hazards models, and cognitive decline, using random effects models, was examined. Results : At baseline, participants reported an average of about one depressive symptom on the CES-D scale (range, 0 to 8). During the 7 years of follow-up, 108 persons developed AD. In analyses that controlled for selected demographic and clinical variables including baseline level of cognitive function, CES-D score was associated with both risk of AD and rate of cognitive decline. For each depressive symptom, risk of developing AD increased by an average of 19%, and annual decline on a global cognitive measure increased by an average of 24%. Conclusions : The results raise the possibility that depressive symptoms in older persons may be associated with risk of developing AD.
TL;DR: It is shown that protein phosphatase 1 (PP1) determines the efficacy of learning and memory by limiting acquisition and favouring memory decline, and inhibition of PP1 prolongs memory when induced after learning, suggesting that PP1 also promotes forgetting.
Abstract: Repetition in learning is a prerequisite for the formation of accurate and long-lasting memory. Practice is most effective when widely distributed over time, rather than when closely spaced or massed. But even after efficient learning, most memories dissipate with time unless frequently used. The molecular mechanisms of these time-dependent constraints on learning and memory are unknown. Here we show that protein phosphatase 1 (PP1) determines the efficacy of learning and memory by limiting acquisition and favouring memory decline. When PP1 is genetically inhibited during learning, short intervals between training episodes are sufficient for optimal performance. The enhanced learning correlates with increased phosphorylation of cyclic AMP-dependent response element binding (CREB) protein, of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and of the GluR1 subunit of the AMPA receptor; it also correlates with CREB-dependent gene expression that, in control mice, occurs only with widely distributed training. Inhibition of PP1 prolongs memory when induced after learning, suggesting that PP1 also promotes forgetting. This property may account for ageing-related cognitive decay, as old mutant animals had preserved memory. Our findings emphasize the physiological importance of PP1 as a suppressor of learning and memory, and as a potential mediator of cognitive decline during ageing.
TL;DR: This work examined the relation between severity of white matter lesions and cognitive decline over a nearly 10‐year period in 563 elderly subjects sampled from the general nondemented Dutch population.
Abstract: The prospect of declining cognitive functions is a major fear for many elderly persons. Cerebral white matter lesions, as commonly found with magnetic resonance imaging, have been associated with cognitive dysfunction in cross-sectional studies. Only a few longitudinal studies using small cohorts confirmed these findings. We examined the relation between severity of white matter lesions and cognitive decline over a nearly 10-year period in 563 elderly subjects sampled from the general nondemented Dutch population. Severity of white matter lesions was scored for periventricular and subcortical regions separately using an extensive semiquantitative scale. Cognitive function was measured by the Mini-Mental State Examination at regular time intervals during 1990 to 2000, and magnetic resonance imaging scans were made in 1995 to 1996. More severe white matter lesions were associated with more rapid cognitive decline over a mean follow-up period of 7.3 years (standard deviation, 1.5). After adjusting for age, gender, educational level, measures of depression, and brain atrophy and infarcts, subjects with severe periventricular white matter lesions experienced cognitive decline nearly three times as fast (0.28 Mini-Mental State Examination points/year [95% confidence interval, 0.20-0.36]) as the average (0.10 points/year [95% confidence interval, 0.09-0.11]). There was no independent relationship between severity of subcortical white matter lesions and rate of cognitive decline.
TL;DR: Age-associated intensification of the links among sensory, sensorimotor and cognitive functions observed both correlationally and experimentally may point to common causes influencing all three functions, including an increase in resource overlap, cross-domain resource competition, and compensatory tradeoffs.
TL;DR: Animals that exercise show an increase in brain-derived neurotrophic factor, a molecule that increases neuronal survival, enhances learning, and protects against cognitive decline.
Abstract: Physical activity, in the form of voluntary wheel running, induces gene expression changes in the brain. Animals that exercise show an increase in brain-derived neurotrophic factor, a molecule that increases neuronal survival, enhances learning, and protects against cognitive decline. Microarray analysis of gene expression provides further support that exercise enhances and supports brain function.
TL;DR: Models combining multiple risk factors should refine the prediction of questionable dementia and persistent cognitive impairment, harbingers of dementia.
Abstract: Background Several studies have shown that individually memory, hippocampal volume, and motor measures presage the onset of dementia. It is unclear if these independently contribute to the prediction of mild cognitive impairment. Objective To determine the ability of memory, hippocampal volume, and a gait speed to independently predict cognitive decline in healthy elderly persons. Design A prospective, longitudinal, observational cohort study with a mean follow-up of 6 years. Participants One hundred eight optimally healthy elderly cognitively intact subjects. Main outcome measures Any cognitive impairment noted on the Clinical Dementia Rating Scale (score = 0.5) or persistent or progressive cognitive impairment. Cox modeling determined if time to onset of cognitive impairment was associated with baseline logical memory II test score (a measure of delayed recall), hippocampal volume (magnetic resonance imaging), or gait speed (time to walk 30 ft [9 m]) independent of age, sex, depression, or the allele producing the epsilon4 type of apolipoprotein E (APOE epsilon4). Results Questionable dementia occurred in 48 participants in a mean (SD) of 3.7 (2.4) years. This progressed to persistent cognitive impairment in 38 of these participants in a mean (SD) of 4.4 (2.4) years. Logical memory II test performance and hippocampal volume each predicted onset of questionable dementia, independent of age and sex. Time to walk 30 ft additionally contributed independently to the prediction of time to onset of persistent cognitive impairment. Possessing the APOE epsilon4 allele and depression did not enter either model significantly. Conclusions Models combining multiple risk factors should refine the prediction of questionable dementia and persistent cognitive impairment, harbingers of dementia. Individuals at risk for cognitive impairment may represent a high-risk group for intervention.
TL;DR: The ability to detect patients at high risk for Alzheimer type dementia among those with minor cognitive impairment increases when data on age and memory function are combined with measures of medial temporal lobe atrophy.
Abstract: Objectives: To investigate whether medial temporal lobe atrophy predicted outcome in patients with minor cognitive impairment and whether assessment of the medial temporal lobe could increase the predictive accuracy of age and delayed recall for outcome. Quantitative and qualitative methods of assessing the medial temporal lobe were also compared. Methods: Patients with minor cognitive impairment older than 50 years (n=31) were selected from a memory clinic and were followed up for on average 1.9 years. The medial temporal lobe was assessed in three different ways: volumetry of the hippocampus, volumetry of the parahippocampal gyrus, and qualitative rating of medial temporal lobe atrophy (MTA). Outcome measures were Alzheimer type dementia or cognitive decline at follow up. Delayed recall was tested with a verbal learning test. Results: Ten patients had experienced cognitive decline at follow up, of whom seven had probable Alzheimer type dementia. All medial temporal lobe measurements were associated with cognitive decline at follow up (p trend analysis between 0.001 (hippocampus) and 0.05 (parahippocampal gyrus)). Only the hippocampal volume and MTA score were associated with Alzheimer type dementia at follow up (p trend analysis respectively 0.003 and 0.01). All medial temporal lobe measurements increased the predictive accuracy of age and the delayed recall score for cognitive decline (p increase in predictive accuracy varied between <0.001 (hippocampus) and 0.02 (parahippocampal gyrus and MTA score)) and the hippocampal volume and the MTA score increased the predictive accuracy of age and the delayed recall score for Alzheimer type dementia (p= 0.02). Conclusions: The ability to detect patients at high risk for Alzheimer type dementia among those with minor cognitive impairment increases when data on age and memory function are combined with measures of medial temporal lobe atrophy. Volumetry of the hippocampus is preferred, but qualitative rating of medial temporal lobe atrophy is a good alternative.
TL;DR: Vitamin E intake, from foods or supplements, is associated with less cognitive decline with age, and there was little evidence of association with vitamin C or carotene intake.
Abstract: Background Previous studies raise the possibility that antioxidants protect against neurodegenerative diseases. Objective To examine whether intake of antioxidant nutrients, including vitamin E, vitamin C, and carotene, is associated with reduced cognitive decline with age. Design Longitudinal population-based study conducted from September 17, 1993, to November 20, 2000, with an average follow-up of 3.2 years. Patients The patients were 2889 community residents, aged 65 to 102 years, who completed a food frequency questionnaire, on average 18 months after baseline. Main Outcome Measure Cognitive change as measured by 4 tests (the East Boston Memory Test, which tests immediate and delayed recall; the Mini-Mental State Examination; and the Symbol Digit Modalities Test) at baseline and 3 years for all participants, and at 6 months for 288 randomly selected participants. Results We used random-effects models to estimate nutrient effects on individual change in the average score of the 4 cognitive tests. The cognitive score declined on average by 5.0 × 10 −2 standardized units per year. There was a 36% reduction in the rate of decline among persons in the highest quintile of total vitamin E intake (−4.3 × 10 −2 standardized units per year) compared with those in the lowest quintile (−6.7 × 10 −2 standardized units per year) ( P = .05), in a model adjusted for age, race, sex, educational level, current smoking, alcohol consumption, total calorie (energy) intake, and total intakes of vitamin C, carotene, and vitamin A. We also observed a reduced decline with higher vitamin E intake from foods ( P = .03 for trend). There was little evidence of association with vitamin C or carotene intake. Conclusion Vitamin E intake, from foods or supplements, is associated with less cognitive decline with age.
TL;DR: Results imply that oxidative damage, specifically the level of superoxide, does play a role in limiting the lifespans of invertebrates such as Drosophila melanogaster and Caenorhabditis elegans, and there is evidence that antioxidant treatment protects against age‐related dysfunction, including cognitive decline.
Abstract: The oxidative stress theory of aging has become increasingly accepted as playing a role in the aging process, based primarily on a substantial accumulation of circumstantial evidence. In recent years, the hypothesis that mitochondrially generated reactive oxygen species play a role in organismal aging has been directly tested in both invertebrate and mammalian model systems. Initial results imply that oxidative damage, specifically the level of superoxide, does play a role in limiting the lifespans of invertebrates such as Drosophila melanogaster and Caenorhabditis elegans. In mammalian model systems, the effect of oxidative stress on lifespan is less clear, but there is evidence that antioxidant treatment protects against age-related dysfunction, including cognitive decline.
TL;DR: Findings indicate that vaccination of AD patients with Aβ42 induces antibodies that have a high degree of selectivity for the pathogenic target structures, and whether vaccination to produce antibodies against β-amyloid will halt the cognitive decline in AD will depend upon clinical assessments over time.
Abstract: To characterize antibodies produced in humans in response to Abeta42 vaccination, we carried out immunohistochemical examinations of the brains of both transgenic mice and human patients with beta-amyloid pathology. We collected sera from patients with Alzheimer disease who received a primary injection of pre-aggregated Abeta42 followed by one booster injection in a placebo-controlled study. Antibodies in immune sera recognized beta-amyloid plaques, diffuse Abeta deposits and vascular beta-amyloid in brain blood vessels. The antibodies did not cross-react with native full-length beta-amyloid precursor protein or its physiological derivatives, including soluble Abeta42. These findings indicate that vaccination of AD patients with Abeta42 induces antibodies that have a high degree of selectivity for the pathogenic target structures. Whether vaccination to produce antibodies against beta-amyloid will halt the cognitive decline in AD will depend upon clinical assessments over time.
01 Jul 2002
TL;DR: The data presented in this review should interest physicians who provide preventive care management to middle-aged and older individuals who seek to maintain cognitive vitality with aging.
Abstract: Cognitive vitality is essential to quality of life and survival in old age. With normal aging, cognitive changes such as slowed speed of processing are common, but there is substantial interindividual variability, and cognitive decline is clearly not inevitable. In this review, we focus on recent research investigating the association of various lifestyle factors and medical comorbidities with cognitive aging. Most of these factors are potentially modifiable or manageable, and some are protective. For example, animal and human studies suggest that lifelong learning, mental and physical exercise, continuing social engagement, stress reduction, and proper nutrition may be important factors in promoting cognitive vitality in aging. Manageable medical comorbidities, such as diabetes, hypertension, and hyperlipidemia, also contribute to cognitive decline in older persons. Other comorbidities such as smoking and excess alcohol intake may contribute to cognitive decline, and avoiding these activities may promote cognitive vitality in aging. Various therapeutics, including cognitive enhancers and protective agents such as antioxidants and anti-inflammatories, may eventually prove useful as adjuncts for the prevention and treatment of cognitive decline with aging. The data presented in this review should interest physicians who provide preventive care management to middle-aged and older individuals who seek to maintain cognitive vitality with aging.
TL;DR: Baseline high levels of depressive symptoms predicted a higher risk of cognitive decline at 4-year follow-up and persistent but not episodic depressive episodes were associated with cognitive decline.
Abstract: Background Depressive symptoms are associated with cognitive decline in elderly people, but the nature of their temporal relationship remains equivocal
Aims To test whether depressive symptoms predict cognitive decline in elderly people with normal cognition
Method The Center for Epidemiologic Study depression scale (CES—D) and the Mini-Mental State Examination (MMSE) were used to evaluate depressive symptomatology and cognitive functioning, respectively A sample of 1003 persons aged 59-71 years and with a MMSE score of 26 or over was selected Cognitive decline was defined as a drop of at least 3 points on the MMSE at 4-year follow-up
Results Baseline high levels of depressive symptoms predicted a higher risk of cognitive decline at 4-year follow-up The MMSE score of participants with depression was more likely to fall below 26 at 2-year follow-up and to remain below at 4-year follow-up than the MMSE score of those without depressive symptoms Persistent but not episodic depressive episodes were associated with cognitive decline
Conclusions High levels of depressive symptoms, when persistent, are associated with cognitive decline in a sample of elderly people
TL;DR: It is indicated that cognitive deficits in the early stages of HIV are small and increase in the later phases of the illness, and that specific patterns of cognitive deficits can be detected with disease progression.
Abstract: This meta-analysis summarizes the broad spectrum of neuropsychological research on HIV disease across a sample of 41 primary studies and an aggregate of 8,616 participants for 10 major neuropsychological ability areas. Analyses of the course of cognitive decline within and across Centers for Disease Control classifications reveals statistically significant cognitive deficits from asymptomatic HIV to AIDS. Effect sizes (Cohen, 1988) were calculated to reflect between-group (asymptomatic, symptomatic, AIDS) differences in each neuropsychological domain. Relatively small effect sizes were obtained for the asymptomatic (0.05–0.21) patients, and generally small to moderate effect sizes were obtained for symptomatic (0.18–0.65) HIV+ patients, with motor functioning exhibiting the greatest effects in this later disease stage. The most notable deficits in cognitive functioning were found in the AIDS group with moderate (attention and concentration) to large (motor functioning) effect sizes with values ranging from 0.42–0.82. Comparison of cognitive functioning as a function of disease progression revealed that motor functioning, executive skills, and information processing speed were among the cognitive domains showing the greatest decline from early to later stages of HIV. These findings indicate that cognitive deficits in the early stages of HIV are small and increase in the later phases of the illness, and that specific patterns of cognitive deficits can be detected with disease progression. These results and their clinical utility are further discussed. (JINS, 2002, 8, 410–424.)
TL;DR: Results showed that L-T4 treatment, administered both sub-chronically and chronically, significantly enhanced the ability of rats to learn a spatial memory task, compared with controls, and reduced the cognitive-impairing effects of scopolamine.
TL;DR: The findings suggest that when older persons complain about their memory and do not show actual cognitive decline, one should be aware that these complaints might reflect psycho-affective or health problems.
TL;DR: It is suggested that long-term use of benzodiazepines is risk factor of increased cognitive decline in the elderly and episodic and recurrent users had lower cognitive scores than nonusers.
Abstract: Several cross-sectional studies have found cognitive impairment in subjects taking benzodiazepines for long periods. However, it is not known whether long-term use of benzodiazepines accelerates cognitive decline in the elderly. The authors addressed this issue in a follow-up study of 1,389 people aged 60 to 70 years recruited from the electoral rolls of the city of Nantes (Epidemiology of Vascular Aging study). Data on cognitive functioning (five cognitive tests), depressive symptoms (Center for Epidemiologic Studies-Depression Scale), anxiety symptoms (Spielberger Inventory Scale), use of psychotropics and other drugs, and tobacco and alcohol consumption were collected at baseline, 2-year, and 4-year examinations. People reporting to take benzodiazepines at one, two and three examinations were classified as episodic, recurrent, and chronic users, respectively. Among the 1,176 subjects (85%) who participated in the three examinations, the proportions of episodic, recurrent, and chronic users were 10%, 6%, and 7%, respectively. Chronic users of benzodiazepines had a significantly higher risk of cognitive decline in the global cognitive test (Mini Mental State Examination) and the two attention tests than nonusers (Mini Mental State Examination: odds ratio [OR] [95% confidence interval (CI)] = 1.9 [1.0-3.5]; Digit Symbol Substitution test: OR [95% CI] = 2.7 [1.6-4.7]; Trail Making test, part B: OR [95% CI] = 2.1 [1.2-3.7]). Overall, episodic and recurrent users had lower cognitive scores than nonusers, but differences were not statistically significant. These results were independent of age, sex, education, alcohol and tobacco use, anxiety and depression scores, and use of psychotropic drugs other than benzodiazepines. The findings suggest that long-term use of benzodiazepines is risk factor of increased cognitive decline in the elderly.
TL;DR: The aim is to study the impact of depression on the wellbeing, disability and use of health services of older adults and to establish a smoking cessation strategy for older adults.
Abstract: Objective: To study the impact of depression on the wellbeing, disability and use of health services of older adults.
Method: Prospective community-based study, using a large (ne2200) sample of the elderly (55–85) in the Netherlands. Using a 3-year follow-up, the effect of depressive symptoms (CES-D) on disability, wellbeing and service utilization was assessed, controlling for competing need-for-care (chronic physical illness, functional limitation and cognitive decline), enabling (partner status, size of the social network, social support and locus of control), and predisposing factors (age, sex and level of education).
Results: Depressive symptoms have considerable impact on the wellbeing and disability of older people and clear economic consequences caused by inappropriate service utilization. Compared with other need-for-care variables the impact of depression is weaker (service utilization), similar (disability) or stronger (wellbeing).
Conclusion: The steeply rising prevalence of competing health risks in later life does not influence the significance of depression.
TL;DR: Among middle-aged subjects, current smoking was inversely and alcohol consumption positively related to psychomotor speed and cognitive flexibility, which suggests that actions to prevent cognitive decline can be taken in middle age.
Abstract: In the elderly, cigarette smoking has been related to reduced cognitive performance and moderate alcohol consumption to increased cognitive performance. It is not clear whether these associations also exist in middle age. The authors examined these relations in a population-based cohort study of 1,927 randomly selected, predominantly middle-aged subjects aged 45-70 years at the time of cognitive testing and living in the Netherlands. From 1995 until 2000, an extensive cognitive battery was administered, and compound scores were calculated. Risk factors had been assessed approximately 5 years previously. Multiple linear regression analyses (in which one unit of the cognitive score = one standard deviation) showed that, after the authors adjusted for age, sex, education, alcohol consumption, and cardiovascular risk factors, current smokers had reduced psychomotor speed (beta = -0.159, 95% confidence interval: -0.071, -0.244; p = 0.0003) and reduced cognitive flexibility (beta = -0.133, 95% confidence interval: -0.035, -0.230; p = 0.008) compared with never smokers. This effect was similar to that of being approximately 4 years older. Alcohol consumption was related to increased speed and better flexibility, especially among women who drank 1-4 alcoholic beverages a day. In conclusion, among middle-aged subjects, current smoking was inversely and alcohol consumption positively related to psychomotor speed and cognitive flexibility. This finding suggests that actions to prevent cognitive decline can be taken in middle age.
TL;DR: The data suggest that memantine, at therapeutically relevant concentrations, can protect against neuronal degeneration induced by β-amyloid.
TL;DR: It is found that aged rats also have deficits in NR2B protein expression and that the protein expression deficit is correlated with their performance in the Morris water maze, and a role for reducedNR2B expression in age-related cognitive decline is suggested.
Abstract: Aged rats are known to have deficits in spatial learning behavior in the Morris water maze. We have found that aged rats also have deficits in NR2B protein expression and that the protein expression deficit is correlated with their performance in the Morris water maze. To test whether this NR2B deficit was sufficient to account for the behavioral deficit, we used antisense oligonucleotides to specifically knock down NR2B subunit expression in the hippocampus of young rats. NR2B antisense treatment diminished NMDA receptor responses, abolished NMDA-dependent long-term potentiation (LTP), and impaired spatial learning. These data demonstrate the important role of NR2B in LTP and learning and memory and suggest a role for reduced NR2B expression in age-related cognitive decline.