Showing papers on "Cognitive decline published in 2000"
TL;DR: The Mini‐Cog, a composite of three‐item recall and clock drawing, was developed as a brief test for discriminating demented from non‐demented persons in a community sample of culturally, linguistically, and educationally heterogeneous older adults.
Abstract: Objectives. The Mini-Cog, a composite of three-item recall and clock drawing, was developed as a brief test for discriminating demented from non-demented persons in a community sample of culturally, linguistically, and educationally heterogeneous older adults.
Subjects. All 129 who met criteria for probable dementia based on informant interviews and 120 with no history of cognitive decline were included; 124 were non-English speakers.
Methods. Sensitivity, specificity, and diagnostic value of the Mini-Cog were compared with those of the Mini-Mental State Exam (MMSE) and Cognitive Abilities Screening Instrument (CASI).
Results. The Mini-Cog had the highest sensitivity (99%) and correctly classified the greatest percentage (96%) of subjects. Moreover, its diagnostic value was not influenced by education or language, while that of the CASI was adversely influenced by low education, and both education and language compromised the diagnostic value of the MMSE. Administration time for the Mini-Cog was 3 minutes vs 7 minutes for the MMSE.
Conclusions. The Mini-Cog required minimal language interpretation and training to administer, and no test forms of scoring modifications were needed to compensate for the extensive linguistic and educational heterogeneity of the sample. Validation in clinical and population-based samples is warranted, as its brevity and ease of administration suggest that the Mini-Cog might be readily incorporated into general practice and senior care settings as a routine ‘cognitive vital signs’ measure. Copyright © 2000 John Wiley & Sons, Ltd.
1,338 citations
TL;DR: An important role for Abeta in mediating initial pathogenic events in AD dementia is supported and treatment strategies targeting the formation, accumulation, or cytotoxic effects of Abeta should be pursued.
Abstract: ContextAlzheimer disease (AD) is characterized neuropathologically by the presence
of amyloid β-peptide (Aβ)–containing plaques and neurofibrillary
tangles composed of abnormal tau protein. Considerable controversy exists
as to whether the extent of accumulation of Aβ correlates with dementia
and whether Aβ alterations precede or follow changes in tau.ObjectivesTo determine whether accumulation of Aβ correlates with the earliest
signs of cognitive deterioration and to define the relationship between Aβ
accumulation and early tau changes.Design, Setting, and PatientsPostmortem cross-sectional study of 79 nursing home residents with Clinical
Dementia Rating (CDR) scale scores of 0.0 to 5.0 who died between 1986 and
1997, comparing the levels of Aβ variants in the cortices of the subjects
with no (CDR score, 0.0 [n = 16]), questionable (CDR score, 0.5 [n = 11]),
mild (CDR score, 1.0 [n = 22]), moderate (CDR score, 2.0 [n = 15]), or severe
(CDR score, 4.0 or 5.0 [n = 15]) dementia.Main Outcome MeasuresLevels of total Aβ peptides with intact or truncated amino termini
and ending in either amino acid 40 (Aβx-40) or 42 (Aβx-42) in 5
neocortical brain regions as well as levels of tau protein undergoing early
conformational changes in frontal cortex, as a function of CDR score.ResultsThe levels of both Aβx-40 and Aβx-42 were elevated even in
cases classified as having questionable dementia (CDR score = 0.5), and increases
of both peptides correlated with progression of dementia. Levels of the more
fibril-prone Aβx-42 peptide were higher than those of Aβx-40 in
nondemented cases and remained higher throughout progression of disease in
all regions examined. Finally, increases in Aβx-40 and Aβx-42 precede
significant tau pathology at least in the frontal cortex, an area chosen for
examination because of the absence of neuritic changes in the absence of disease.ConclusionsIn this study, levels of total Aβx-40 and Aβx-42 were elevated
early in dementia and levels of both peptides were strongly correlated with
cognitive decline. Of particular interest, in the frontal cortex, Aβ
was elevated before the occurrence of significant tau pathology. These results
support an important role for Aβ in mediating initial pathogenic events
in AD dementia and suggest that treatment strategies targeting the formation,
accumulation, or cytotoxic effects of Aβ should be pursued.
1,308 citations
TL;DR: The results indicate that the combination of cerebral metabolic rates and genetic risk factors provides a means for preclinical AD detection that will assist in response monitoring during experimental treatments.
Abstract: The major known genetic risk for Alzheimer's disease (AD), apolipoprotein E-4 (APOE-4), is associated with lowered parietal, temporal, and posterior cingulate cerebral glucose metabolism in patients with a clinical diagnosis of AD. To determine cognitive and metabolic decline patterns according to genetic risk, we investigated cerebral metabolic rates by using positron emission tomography in middle-aged and older nondemented persons with normal memory performance. A single copy of the APOE-4 allele was associated with lowered inferior parietal, lateral temporal, and posterior cingulate metabolism, which predicted cognitive decline after 2 years of longitudinal follow-up. For the 20 nondemented subjects followed longitudinally, memory performance scores did not decline significantly, but cortical metabolic rates did. In APOE-4 carriers, a 4% left posterior cingulate metabolic decline was observed, and inferior parietal and lateral temporal regions demonstrated the greatest magnitude (5%) of metabolic decline after 2 years. These results indicate that the combination of cerebral metabolic rates and genetic risk factors provides a means for preclinical AD detection that will assist in response monitoring during experimental treatments.
737 citations
TL;DR: The Hospital Elder Life Program, a new model of care designed to prevent functional and cognitive decline of older persons during hospitalization, is described.
Abstract: OBJECTIVES: To describe the Hospital Elder Life Program, a new model of care designed to prevent functional and cognitive decline of older persons during hospitalization.
PROGRAM STRUCTURE AND PROCESS: All patients aged ≥ 70 years on specified units are screened on admission for six risk factors (cognitive impairment, sleep deprivation, immobility, dehydration, vision or hearing impairment). Targeted interventions for these risk factors are implemented by an interdisciplinary team-including a geriatric nurse specialist, Elder Life Specialists, trained volunteers, and geriatricians—who work closely with primary nurses. Other experts provide consultation at twice-weekly interdisciplinary rounds.
INTERVENTION: Adherence is carefully tracked. Quality assurance procedures and performance reviews are an integral part of the program.
PROGRAM OUTCOMES: To date, 1507 patients have been enrolled during 1716 hospital admissions. The overall intervention adherence rate was 89% for at least partial adherence with all interventions during 37,131 patient-days. Our results indicate that only 8% of admissions involved patients who declined by 2 or more points on MMSE and only 14% involved patients who declined by 2 or more points on ADL score. Comparative results for the control group from the clinical trial were 26% and 33%, and from previous studies 14 to 56% and 34 to 50% for cognitive and functional decline, respectively. Effectiveness of the program for delirium prevention and of the program's nonpharmacologic sleep protocol have been demonstrated previously.
CONCLUSIONS: These results suggest that the Hospital Elder Life Program successfully prevents cognitive and functional decline in at-risk older patients. The program is unique in its hospital-wide focus; in providing skilled staff and volunteers to implement interventions; and in targeting practical interventions toward evidence-based risk factors. Future studies are needed to evaluate cost-effectiveness and long-term outcomes of the program as well as its effectiveness in non-hospital settings.
661 citations
TL;DR: It is proposed that cerebral ischemia or oligemia may promote Alzheimer type of changes in the aging brain, and that management of peripheral vascular disease is important in the treatment or prevention of Alzheimer's disease or mixed dementia.
530 citations
TL;DR: Diabetes is associated with lower levels of cognitive function and greater cognitive decline among older women and women who had diabetes for more than 15 years had a 57% to 114% greater risk of major cognitive decline.
Abstract: Background The long-term effect of type 2 diabetes on cognitive function is uncertain. Objective To determine whether older women with diabetes have an increased risk of cognitive impairment and cognitive decline. Design Prospective cohort study. Setting Four research centers in the United States (Baltimore, Md; Portland, Ore; Minneapolis, Minn; and the Monongahela Valley, Pennsylvania). Participants Community-dwelling white women 65 years and older (n = 9679). Measurements Physician-diagnosed diabetes and other aspects of health history were assessed by interview. Three tests of cognitive function, the Digit Symbol test, the Trails B test, and a modified version of the Mini-Mental State Examination (m-MMSE), were administered at baseline and 3 to 6 years later. Change in cognitive function was defined by the change in the score for each test. Major cognitive decline was defined as the worst 10th percentile change in the score for each test. Results Women with diabetes (n = 682 [7.0%]) had lower baseline scores than those without diabetes on all 3 tests of cognitive function (Digit Symbol and Trials B tests, P P = .03) and experienced an accelerated cognitive decline as measured by the Digit Symbol test ( P P = .03). Diabetes was also associated with increased odds of major cognitive decline as determined by scores on the Digit Symbol (odds ratio = 1.63; 95% confidence interval, 1.20-2.23) and Trails B (odds ratio, 1.74; 95% confidence interval, 1.27-2.39) tests when controlled for age, education, depression, stroke, visual impairment, heart disease, hypertension, physical activity, estrogen use, and smoking. Women who had diabetes for more than 15 years had a 57% to 114% greater risk of major cognitive decline than women without diabetes. Conclusion Diabetes is associated with lower levels of cognitive function and greater cognitive decline among older women.
506 citations
TL;DR: Patients with probable Alzheimer's disease showed a highly significant reduction in the integrity of the association white matter fibre tracts, such as the splenium of the corpus callosum, superior longitudinal fasciculus, and cingulum, compared with normal controls.
Abstract: A novel MRI method-diffusion tensor imaging-was used to compare the integrity of several white matter fibre tracts in patients with probable Alzheimer's disease. Relative to normal controls, patients with probable Alzheimer's disease showed a highly significant reduction in the integrity of the association white matter fibre tracts, such as the splenium of the corpus callosum, superior longitudinal fasciculus, and cingulum. By contrast, pyramidal tract integrity seemed unchanged. This novel finding is consistent with the clinical presentation of probable Alzheimer's disease, in which global cognitive decline is a more prominent feature than motor disturbance.
480 citations
TL;DR: D(2) receptor binding is a more important factor than chronological age in accounting for variation in cognitive performance across the adult lifespan, and changes in dopamine neurotransmission play an important role in aging-related cognitive decline.
Abstract: OBJECTIVE: The study examined the influence of losses in dopaminergic function on age-related cognitive deficits. METHOD: Eleven healthy subjects (21–68 years of age) completed a set of cognitive tasks used to assess perceptual speed and episodic memory. D2 receptor binding was measured in the caudate and the putamen by using positron emission tomography. RESULTS: A gradual age-related deterioration was found for all cognitive tasks and for D2 binding in both striatal structures. Statistical control of D2 binding eliminated the age-related cognitive variation, whereas residual effects of D2 binding were seen after the analysis controlled for age. CONCLUSIONS: D2 receptor binding is a more important factor than chronological age in accounting for variation in cognitive performance across the adult lifespan. Changes in dopaminergic neurotransmission play an important role in aging-related cognitive decline.
449 citations
TL;DR: Advances in the understanding of this putative relation between inadequate vitamin status and loss of cognitive function in the elderly are likely to be slow and may depend on the outcomes of both prospective studies and longitudinal studies in which nutritional intervention is provided before cognitive decline occurs.
448 citations
TL;DR: Surprisingly, both healthy and demented women with low education seem to benefit most from HRT, and the interactions of HRT with age, menopausal status and existing protective factors for cognitive decline and Alzheimer's disease are investigated.
421 citations
TL;DR: It was concluded that the course of life-span changes in cognition are affected by education, and among individuals with a low level of education, best neuropsychological test performance is observed at an older age than among higher-educated subjects.
TL;DR: A low-dose regimen of prednisone is not useful in the treatment of AD and subjects treated withprednisone showed behavioral decline compared with those in the placebo group.
Abstract: Background Laboratory and epidemiologic studies suggest that anti-inflammatory/immunosuppressive therapy may be useful in the treatment of AD. In preliminary studies, a regimen of low to moderate dose prednisone was found to suppress peripheral inflammatory markers without adverse effects in subjects with AD. Methods We conducted a randomized, placebo-controlled multicenter trial to determine whether prednisone treatment slowed the rate of cognitive decline in AD. The active treatment regimen consisted of an initial dose of 20 mg of prednisone daily for 4 weeks tapered to a maintenance dose of 10 mg daily for 1 year, followed by gradual withdrawal during an additional 16 weeks. The primary outcome measure was the 1-year change in the cognitive subscale of the AD Assessment Scale. Results A total of 138 subjects were randomized to the drug and placebo groups. There was no difference in cognitive decline between the prednisone and placebo treatment groups in the primary intent-to-treat analysis, or in a secondary analysis considering completers only. Subjects treated with prednisone showed behavioral decline compared with those in the placebo group. Conclusion A low-dose regimen of prednisone is not useful in the treatment of AD.
TL;DR: It is suggested that repeated treatment with estrogen and progesterone initiated within a specific period of time after the loss of ovarian function may be effective at preventing specific negative effects of hormone deprivation on brain aging and cognitive decline.
TL;DR: There is sufficient evidence to take seriously the possibility that depression is a risk factor for dementia and cognitive decline and further work is needed to examine depression as a prodrome of vascular dementia, depression as an early reaction to perceived cognitive decline, the effects of depression on the threshold for manifesting dementia, and Depression as a source of hippocampal damage through a glucocorticoid cascade.
Abstract: Background: It is generally accepted that depression can be associated with significant cognitive deficits and that depression can be comorbid with dementia. Objective:<
TL;DR: There is growing evidence that chronic, heavy, recreational use of ecstasy is associated with sleep disorders, depressed mood, persistent elevation of anxiety, impulsiveness and hostility, and selective impairment of episodic memory, working memory and attention.
Abstract: Rationale: Recreational use of "ecstasy" (3,4- methylenedioxymethamphetamine; MDMA) has become increasingly widespread. Until recently, however, little was known about the possible persistent psychological effects of extensive use of this drug. Objective: The aim of the present review is to evaluate recent empirical evi- dence concerning the persistent psychological sequelae of recreational ecstasy use. Methods: The methodologies of open trial studies of recreational ecstasy users are evaluated and reports of the presence or absence of per- sistent psychological problems are related to the extent of past exposure to ecstasy. Results: There is growing evidence that chronic, heavy, recreational use of ecstasy is associated with sleep disorders, depressed mood, per- sistent elevation of anxiety, impulsiveness and hostility, and selective impairment of episodic memory, working memory and attention. There is tentative evidence that these cognitive deficits persist for at least 6 months after abstinence, whereas anxiety and hostility remit after a year of abstinence. The possibility that some of these psychological problems are caused by ecstasy-induced neurotoxicity is supported by preclinical evidence of MDMA-induced neurotoxicity and behavioural deficits, evidence of depleted serotonin in heavy ecstasy users, and by dose-response relationships between the extent of exposure to ecstasy and the severity of cognitive impair- ments. Conclusions: An increasing number of young, heavy ecstasy users are at significant risk of persistent cognitive impairments and disturbances of affect and personality. Some of these problems may remit after ab- stinence, but residual neurotoxicity and decline of sero- tonergic function with age may result in recurrent psy- chopathology and premature cognitive decline.
TL;DR: In a subgroup of more highly educated elderly people, depression may be an early manifestation of Alzheimer's disease before cognitive symptoms become apparent, but only in subjects with higher levels of education.
Abstract: Background: Depression may be associated with cognitive decline in elderly people with impaired cognition Aims: To investigate whether depressed elderly people with normal cognition are at increased risk of cognitive decline and Alzheimer's disease Methods: Two independent samples of older people with normal cognition were selected from the community-based Amsterdam Study of the Elderly (AMSTEL) and the Longitudinal Aging Study Amsterdam (LASA) In AMSTEL, depression was assessed by means of the Geriatric Mental State Schedule Clinical diagnoses of incident Alzheimer's disease were made using a two-step procedure In LASA, depression was assessed with the Center for Epidemiologic Studies Depression Scale Cognitive decline was defined as a drop of ≥ 3 on the Mini-Mental State Examination at follow-up Results: Both in the AMSTEL and the LASA sample, depression was associated with an increased risk of Alzheimer's disease and cognitive decline, respectively, but only in subjects with higher levels of education Conclusions: In a subgroup of more highly educated elderly people, depression may be an early manifestation of Alzheimer's disease before cognitive symptoms become apparent Declaration of interest: Grants detailed in Acknowledgements No conflict of interest
TL;DR: It is shown, for the first time, that in PD, alpha-synuclein-positive cortical LBs are associated with cognitive impairment independent of AD-type pathology.
Abstract: Amygdala, hippocampus and six cortical gyri were examined for the Lewy body (LB) degeneration and Alzheimer’s disease (AD) type changes in 45 patients with Parkinson’s disease (PD). For detection of LBs, the brain areas were stained with an antibody against alpha-synuclein. The extent of neuropathological lesions was investigated in relation to cognitive dysfunction and apolipoprotein E (apoE) ɛ4 allele dosage. At least one cortical LB was found in 95% of cases (43/45). Furthermore, 40% of cases (18/45) had histological findings of definite AD (CERAD class C). Those PD cases with the apoE ɛ4 allele had a significantly greater number of cortical LBs than those without the apoE ɛ4 allele, but this was statistically significant only in precentral, angular and temporal gyri. The LB density correlated better with the number of plaques than with the density of tangles. The number of LBs in several cortical areas correlated significantly with the cognitive impairment. In stepwise linear regression analysis, the number of LBs in the cingulate gyrus and the amount of tangles in the temporal cortex remained statistically significant. When the CERAD class C was excluded, the correlation between cognitive decline and the number of LBs in cortical areas became even more pronounced. A stepwise linear regression analysis in these cases found the number of LBs in the frontal gyrus to be the statistically most significant predictor of cognitive impairment. This study shows, for the first time, that in PD, alpha-synuclein-positive cortical LBs are associated with cognitive impairment independent of AD-type pathology.
TL;DR: Estrogen use was associated with less cognitive decline among ε4-negative women but not ε 4-positive women, and potential mechanisms, including carotid atherosclerosis, by which ε3 may interact with estrogen and cognition warrant further investigation.
Abstract: Objective: APOE-e4 increases the risk of cognitive decline, while elderly women who take estrogen may have less risk of cognitive decline. The authors sought to determine whether estrogen use modifies the association between APOE -e4 and cognitive decline. Method:— As part of the Cardiovascular Health Study, 3,393 Medicare-eligible women (≥65 years) were randomly selected and recruited from Sacramento County, CA; Washington County, MD; Forsyth County, NC; and Pittsburgh, PA. Cognitive testing was administered annually; the authors studied the 2,716 women with cognitive testing on ≥2 visits. They analyzed change in score on the Modified Mini-Mental State Examination (3MS) as a function of estrogen use, APOE genotype, and baseline common and internal carotid artery wall thickening. Results: A total of 297 (11%) women were current estrogen users and 336 (12%) were past estrogen users. Over the 6-year average follow-up, baseline current users declined 1.5 points on the 3MS whereas never users declined 2.7 points ( p = 0.023). Compared with e4-negative women, e4-positive women had a greater adjusted hazard ratio of cognitive impairment (3MS p = 0.037). Among e4-negative women, current estrogen use reduced the risk of adjusted cognitive impairment compared with never users by almost half (HR = 0.59; 95% CI, 0.36 to 0.99), whereas, it did not reduce the risk among e4-positive women (current use, HR = 1.33; 95% CI, 0.74 to 2.42). Compared with never use, current estrogen use was associated with less internal and common carotid wall thickening in e4-negative women but not in e4-positive women ( p for interaction Conclusions: Estrogen use was associated with less cognitive decline among e4-negative women but not e4-positive women. Potential mechanisms, including carotid atherosclerosis, by which e4 may interact with estrogen and cognition warrant further investigation.
TL;DR: To investigate prevalence of “cognitive impairment, no dementia” (CIND) in the Italian older population, evaluating the association with cardiovascular disease and the impact on activities of daily living (ADL).
Abstract: OBJECTIVES: To investigate prevalence of “cognitive impairment, no dementia” (CIND) in the Italian older population, evaluating the association with cardiovascular disease and the impact on activities of daily living (ADL). CIND may provide pathogenic clues to dementia and independently affect ADL.
DESIGN: Cross-sectional examination in the context of the Italian Longitudinal Study on Aging.
SETTING: Random population sample from eight Italian municipalities.
PARTICIPANTS: A total of 3425 individuals aged 65–84 years, residing in the community or institutionalized.
MEASUREMENTS: Study participants were screened for cognitive impairment by using the Mini-Mental State Examination. Trained neurologists examined those scoring <24. CIND diagnosis relied on clinical and neuropsychological examination, informant interview, and assessment of functional activities. Age-related cognitive decline (ARCD) was diagnosed in CIND cases without neuropsychiatric disorders responsible for the cognitive impairment.
RESULTS: Prevalence was 10.7% for CIND and 7.5% for ARCD, increased with age, and was higher in women. Age (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.06-1.12), stroke (OR, 2.05; 95% CI, 1.26-3.35) and heart failure (OR, 1.73; 95% CI, 1.11-2.68) were significantly and positively associated with CIND at multivariate analysis. Education (OR, 0.61; 95% CI, 0.56-0.65) and smoking (OR, 0.72; 95% CI, 0.54-0.98) showed a negative correlation. Age and myocardial infarction were positively associated with ARCD, whereas a negative correlation was found for education and smoking. The effect of smoking was no more significant either on CIND or ARCD considering current habits or “pack year” exposure. CIND showed an independent impact on ADL (OR, 1.88; 95% CI, 1.41-2.49).
CONCLUSIONS: CIND is very frequent in older people. The effect of demographic variables and vascular conditions offers opportunities for prevention. The association with functional impairment is useful to evaluate the burden of disability and healthcare demands. J Am Geriatr Soc 48:775–782, 2000.
TL;DR: The data suggest that even typical recreational doses of ecstasy are sufficient to cause neurotoxicity in humans, and raise concern that use of ecstasy possibly in conjunction with cannabis may lead to cognitive decline in otherwise healthy young people.
Abstract: Objectives—Ecstasy(3,4-methylenedioxymethamphetamine (MDMA) and related congerers: MDA, MDEA) is the name given to a group of popular recreational drugs. Animal data raise concern about neurotoxic eVects of high doses of ecstasy on central serotonergic systems. The threshold dose for neurotoxicity in humans is not clear and serotonin is involved in several functions including cognition. The purpose of this study was to investigate cognitive performance in a group of typical recreational ecstasy users. Methods—A comprehensive cognitive test battery was administered to 28 abstinent ecstasy users with concomitant use of cannabis only and to two equally sized matched groups of cannabis users and non-users. The sample consisted of ecstasy users with a typical recreational use pattern and did not include very heavy users. Results—Ecstasy users were unimpaired in simple tests of attention (alertness). However, they performed worse than one or both control groups in the more complex tests of attention, in memory and learning tasks, and in tasks reflecting aspects of general intelligence. Heavier ecstasy and heavier cannabis use were associated with poorer performance in the group of ecstasy users. By contrast, the cannabis users did not diVer significantly in their performance from the non-users. Conclusions—The present data raise concern that use of ecstasy possibly in conjunction with cannabis may lead to cognitive decline in otherwise healthy young people. Although the nature of the emerging cognitive disturbance is not yet clear, an impairment of working memory might be the common denominator underlying or contributing to declines of performance in various tasks. The cognitive disturbance is likely to be related to the well recognised neurotoxic potential of ecstasy. The data suggest that even typical recreational doses of ecstasy are suYcient to cause neurotoxicity in humans. (J Neurol Neurosurg Psychiatry 2000;68:719‐725)
TL;DR: Neurocognitive dysfunction is a frequently occurring complication of coronary artery bypass grafting and the etiologic contribution of cardiopulmonary bypass to this complication will remain unclear until a randomized trial that directly compares off-pump and on-p pump bypass surgery is carried out.
TL;DR: A longitudinal study of age-related decline in intellectual function and MRI at age 80 years finds that periventricular and deep white-matter hyperintensities are related to decline in intelligence but, in healthy octogenarians, the cumulative effect of these features alone explains only a small part of the large differences among individuals in age- related decline in Intelligence.
TL;DR: The objective is to determine whether systemic oxidative stress status is associated with cognitive decline and to investigate the role of oxidative stress in cognitive decline.
Abstract: OBJECTIVE: To determine whether systemic oxidative stress status is associated with cognitive decline.
DESIGN: A longitudinal population-based study.
SETTING: A cohort study of older subjects in Nantes, France.
PARTICIPANTS: A total of 1166 high cognitive functioning subjects aged 60 to 70 in the Etude du Vieillissement Arteriel (EVA) cohort with a 4 year follow-up.
MEASUREMENTS: Subjects completed a baseline interview and a global cognitive test (Mini-Mental Status Examination (MMSE)). Blood samples were obtained at baseline to determine plasma levels of selenium, carotenoids, thiobarbituric acid reactant substances (TBARS), an indicator of lipoperoxidation, and red blood cell vitamin E. Risk of cognitive decline, defined as a loss of 3 points in MMSE score between baseline and the 4 year follow-up, was assessed by oxidative stress level.
RESULTS: Subjects with the highest levels of TBARS show an increased risk of cognitive decline (adjusted odds ratio (OR) = 2.25; confidence interval (CI) 95% = 1.26–4.02). This result is reinforced in the lower antioxidant status subgroup. Subjects with low levels of selenium have an increased risk of cognitive decline (OR = 1.58; CI 95% = 1.08–2.31) after adjustment for various confounding factors.
CONCLUSIONS: These results suggest that increased levels of oxidative stress and/or antioxidant deficiencies may pose risk factors for cognitive decline. The direct implication of oxidative stress in vascular and neurodegenerative mechanisms that lead to cognitive impairment should be further explored.
TL;DR: Despite an increase in the age of the cardiac surgical population, the reported incidence of cognitive dysfunction after cardiac surgery seems to have fallen in recent years, and recognition that certain equipment, surgical practices and patient factors contribute to neurological morbidity has prompted 'neuroprotective' interventions.
Abstract: The neurological complications of cardiac surgery are associated with significantly increased mortality, morbidity and resource utilization. The use of new surgical techniques, introduction of wider indications for surgery and increased public expectation has led to an increase in the average age of cardiac surgical patients and an increased incidence of repeat procedures. With these changes has come an increased risk of neurological complications. The likelihood of perioperative stroke varies between 1% and 5% in most published series and is dependent on a multitude of risk factors. Of these, patient age, aortic atheroma, symptomatic cerebrovascular disease, diabetes mellitus and the type of surgery appear to be most important. Cognitive deterioration after cardiac surgery is far more common, affecting as many as 80% of patients a few days after surgery and persisting in one-third. Despite an increase in the age of the cardiac surgical population, the reported incidence of cognitive dysfunction after cardiac surgery seems to have fallen in recent years. Whether this is a real phenomenon or the result of changes in the use of psychometric testing and the definition of cognitive decline remains unclear. Recognition that certain equipment, surgical practices and patient factors contribute to neurological morbidity has prompted 'neuroprotective' interventions. Some of these (e.g. arterial line filtration and alpha-stat management) have been shown to improve outcome. Despite these measures, a small number of patients will inevitably sustain cerebral injury during otherwise successful cardiac surgery. Although pharmacological neuroprotection may, in the future, offer some of these patients an improved outcome, it is unlikely that any single agent will prevent neurological injury. In the meantime, the CNS complications of cardiac surgery remain a fertile area of research.
TL;DR: The evidence from two prospective population-based studies investigating the putative role of vascular risk factors and markers of vascular disease in the development of cognitive decline and (subtypes of) dementia, and the Rotterdam Scan are summarized.
Abstract: Over the last decade evidence has been accumulating for an involvement of vascular mechanisms or vascular pathology in the etiology of cognitive impairment and Alzheimer’s disease, in particular in elderly subjects. Epidemiological studies have largely contributed to these notions. In this paper the evidence from two such prospective population-based studies is summarized. In the Rotterdam Study we investigated the putative role of vascular risk factors and markers of vascular disease in the development of cognitive decline and (subtypes of) dementia, and performed an initial study on the determinants and clinical significance of cerebral white matter lesions. Based on these results, we then initiated the Rotterdam Scan, in which causes and consequences of degenerative and vascular brain changes are investigated prospectively. A discussion of potential underlying mechanisms and of related findings from other studies falls outside the scope of this paper, but has been the subject of several recently published reviews.1,2
TL;DR: A relatively high incidence of hallucinations and delusions in patients diagnosed with probable AD is found and it is suggested that specific neurologic signs, cognitive abilities, and accelerated decline may be predictive markers for their occurrence.
Abstract: Objective: To examine the incidence of and risk factors for hallucinations and delusions associated with patients clinically diagnosed with probable AD. Background: Estimates of the incidence of psychosis in AD range widely from 10% to 75%. The risk factors for psychosis of AD are not known, although multiple studies indicate that AD patients with psychosis demonstrate greater cognitive and functional impairment. Methods: The authors conducted psychiatric evaluations of 329 patients with probable AD from the University of California at San Diego Alzheimer’s Disease Research Center to determine the incidence of hallucinations and delusions. They examined data from annual clinical and neuropsychological evaluations to determine whether there were specific risk factors for the development of hallucinations and delusions. Results: Using Cox survival analyses, the cumulative incidence of hallucinations and delusions was 20.1% at 1 year, 36.1% at 2, 49.5% at 3, and 51.3% at 4 years. Parkinsonian gait, bradyphrenia, exaggerated general cognitive decline, and exaggerated semantic memory decline were significant predictors. Age, education, and gender were not significant predictors. Conclusions: The authors found a relatively high incidence of hallucinations and delusions in patients diagnosed with probable AD and suggest that specific neurologic signs, cognitive abilities, and accelerated decline may be predictive markers for their occurrence.
TL;DR: In this article, the authors explored the impact of topiramate on tests of intellect and other cognitive processes and found that the greatest changes were for verbal IQ, verbal fluency, and verbal learning.
Abstract: OBJECTIVE To explore the impact of topiramate on tests of intellect and other cognitive processes. METHODS This was a retrospective study. The neuropsychological test scores of 18 patients obtained before and after the introduction of treatment with topiramate (median dose 300 mg) were compared with changes in test performance of 18 patients who had undergone repeat neuropsychological assessments at the same time intervals. Complaints of cognitive decline precipitated referral for reassessment in five cases in the topiramate treated group. The groups were matched for age and intellectual level at the time of the first assessment. Patients were assessed using the WAIS-R, tests of verbal and non-verbal memory, language, and perceptual processing. A subgroup of patients underwent a brief reassessment after the withdrawal or substantial reduction of topiramate. RESULTS Repeat assessments in those taking topiramate were associated with a significant deterioration in many domains, which were not seen in the comparison group. The greatest changes were for verbal IQ, verbal fluency, and verbal learning (p CONCLUSIONS In our patient group topiramate had a negative impact on cognition which was consistent with subjective complaints of patients. Tests requiring verbal processing seemed especially sensitive to the drug. A decline in verbal intellect (VIQ), a measure which has been considered by some to be insensitive to antiepileptic drug effects, was particularly striking. Caution is warranted in the interpretation of the findings due to methodological limitations of the study design. Further investigation of mediating factors such as serum concentrations, comedication, and other potential risk factors, however, is needed to enable appropriate targeting of treatment with this effective antiepileptic agent.
TL;DR: Women with high serum concentrations of non-protein-bound and bioavailable oestradiol, but not testosterone, were less likely to develop cognitive impairment than women with low concentrations, and this finding supports the hypothesis that higher concentrations of endogenous oestrogens prevent cognitive decline.
TL;DR: The loss of ChAT-immunoreactive neurons in the basal forebrain was coupled with simultaneous deficits in behavioral flexibility on a spatial task occurring for the first time around 6 months of age, suggesting that the loss of cholinergic function and the simultaneous decrease in trkA immunoreactivity in basal fore brain may directly correlate with cognitive impairment in the Ts65Dn mouse.
TL;DR: The effects on mortality of cognitive impairment and 3-year declines in cognitive function were examined among community-dwelling adults aged 68 years or more and it was not clear whether the decline per se signaled an unfavorable prognosis not accounted for by the resulting impairment level.
Abstract: The effects on mortality of cognitive impairment and 3-year declines in cognitive function were examined among community-dwelling adults aged 68 years or more. Data were taken from a population-based cohort study that enrolled noninstitutionalized elderly residents of New Haven, Connecticut, and followed them by conducting in-home interviews in 1982, 1985, 1988, and 1994. The cognitive function of 1,997 respondents was assessed by using the 30-point Mini-Mental State Examination in 1985; 1,372 respondents (86% of those alive) were retested in 1988. Responses were classified as high normal (28-30), low normal (24-27), mild impairment (18-23), or severe impairment (0-17); cognitive decline was defined as a transition to a lower category. After control for multiple potential confounders, both severe and mild cognitive impairment were strongly predictive of subsequent mortality among respondents aged less than 80 years. Upon closer examination, the elevated mortality risk was observed primarily among respondents whose cognitive decline was recent rather than among those whose cognitive performance was compromised but stable. Among respondents aged 80 years or more, declines to severe cognitive impairment were predictive of mortality, but it was not clear whether the decline per se signaled an unfavorable prognosis not accounted for by the resulting impairment level. Cognitive declines, especially those in the young elderly, have a marked adverse impact on survival.