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Showing papers on "Cognitive decline published in 1994"


Journal ArticleDOI
TL;DR: The burgeoning of interest in the elderly and the massive expansion of clinical and research work in the field of dementia in the eighties led to a widely expressed need for the development of criteria to categorize a group of subjects with memory problems falling short of dementia, and the suggested criteria have proved controversial.
Abstract: In 1962, based on a study of nursing home residents, Kral suggested a distinction between benign and malignant senescent forgetfulness, the latter evolving to dementia and early death and the former remaining relatively static. Although this concept was never operationally described or validated, it clearly rang true with those working with the nascent specialty of geriatric psychiatry and rapidly entered standard textbooks on the subject. The burgeoning of interest in the elderly and the massive expansion of clinical and research work in the field of dementia in the eighties led to a widely expressed need for the development of criteria to categorize a group of subjects with memory problems falling short of dementia. The National Institute of Mental Health (NIMH) responded with the formation of a working group that published its suggested criteria for what Crook et al. (1986) called “age-associated memory impairment” (AAMI). Although some of the detailed components of these criteria have proved controversial, the term has been increasingly quoted in relevant literature and has given rise to specific studies. It has led to wide discussion, and related entities have been incorporated both in the draft of DSM-IV (as “aging-associated cognitive decline [AACD]” [American Psychiatric Association, 1993], an “additional condition that may be the focus of clinical attention”) and in the research criteria for ICD-10 (World Health Organization, 1993), where it is potentially classifiable under FO6.7 Mild Cognitive Disorder, although this does not specifically give aging as a cause. In arriving at our provisional criteria we have drawn to a great degree on these and other related publications that we are pleased to acknowledge.

623 citations


Book
01 Jul 1994
TL;DR: Human Error in Medicine: A Frontier for Change is concerned with the causes and reduction of human errors in clinical practice and the consequences of these errors on patients and the profession.
Abstract: Contents: J.T. Reason, Foreword. M.S. Bogner, Introduction. L.L. Leape, The Preventability of Medical Injury. J.A. Perper, Life-Threatening and Fatal Therapeutic Misadventures. H. Van Cott, Human Errors: Their Causes and Reduction. N. Moray, Error Reduction as a Systems Problem. G. Vroman, I. Cohen, N. Volkman, Misinterpreting Cognitive Decline in the Elderly: Blaming the Patient. R.L. Klatzky, J. Geiwitz, S.C. Fischer, Using Statistics in Clinical Practice: A Gap Between Training and Application. T.B. Sheridan, J.M. Thompson, People Versus Computers in Medicine. J.W. Senders, Medical Devices, Medical Errors, and Medical Accidents. D.I. Serig, Radiopharmaceutical Misadministrations: What's Wrong? D.M. Gaba, Human Error in Dynamic Medical Domains. R.L. Helmreich, H-G. Schaefer, Team Performance in the Operating Room. R.I. Cook, D.D. Woods, Operating at the Sharp End: The Complexity of Human Error. G.P. Krueger, Fatigue, Performance, and Medical Error. W.A. Hyman, Errors in the Use of Medical Equipment. M.H. Applegate, Diagnosis-Related Groups: Are Patients in Jeopardy? M.S. Bogner, Human Error in Medicine: A Frontier for Change. J. Rasmussen, Afterword.

591 citations


Journal ArticleDOI
TL;DR: Cognitive deterioration is slow during the early and very late stages of Alzheimer's disease and more rapid during the middle stages, suggesting that treatment trials and attempts to identify subgroups are affected.
Abstract: Objective: This study measured the annual rate ofcognitive change in patients with Alzheimer’s disease and determined the effects ofclinical variables on that rate. It also compared the ability of two cognitive scales to measure change over the entire range of dementia severity. Method: The cognitive subscale of the Alzheimer’s Disease Assessment Scale and the Blessed test for information memory and concentration were given to 1 1 1 patients with Alzheimer’s disease and 72 nondemented elderly comparison subjects at 6-month intervals for up to 90 months. Longitudinal changes in scores on the cognitive subscale were measured with several different methods of data analysis. Results: For the patients with Alzheimer’s disease, the annual rate of change in cognitive subscale scores showed a quadratic relationship with dementia severity in which deterioration was slower for mildly and severely demented patients than for patients with moderate dementia. Gender, age at onset, and family history of dementia 1 had no effect on the rate of cognitive deterioration. The comparison group showed a slight improvement in cognitive performance over time. All data analytic methods gave similar results. The cognitive subscale of the Alzheimer’s Disease Assessment Scale was more sensitive to change in both mild and severe dementia than was the Blessed test. Conclusions: These results suggest that cognitive deterioration is slow during the early and very late stages of Alzheimer’s disease and more rapid during the middle stages. No clinical variables other than degree of cognitive impairment and previous rate of cognitive decline predicted rate of deterioration. These results have implications for treatment trials and attempts to identify subgroups. (Am J Psychiatry 1994; 151:390-396)

419 citations


Journal ArticleDOI
TL;DR: The results suggest that the pattern of cognitive decline in MS is a function of the location of demyelinating lesions within the cerebral hemispheric white matter.
Abstract: Conceptual reasoning deficits are common in patients with multiple sclerosis (MS) and are typically associated with focal lesions involving the frontal lobes. In this study, we predicted that MS patients with frontal white matter lesions (MS-F) would be more impaired on a standard conceptual reasoning task (Wisconsin Card Sorting Test; WCST) than patients with minimal frontal lesions (MS-NF), even if the total cerebral lesion area (TLA), measured from MRI, was equivalent across groups. We subdivided 43 definite MS patients into three groups based on MRI findings: seven in the MS-F group (mean TLA = 41.4 cm2) and seven in the MS-NF group (mean TLA = 50.0 cm2); 29 MS patients served as a low lesion burden control group (MS-C; mean TLA = 6.4 cm2). The groups did not differ with regard to demographic and illness characteristics. Although the three subgroups obtained comparable scores on a measure of global cognitive functioning (verbal intelligence), the MS-F group achieved significantly fewer categories and made more total errors on the WCST than did the MS-NF and MS-C groups. The MS-F group made significantly more perseverative responses than the MS-C group and nonsignificantly more than the MS-NF group. These results suggest that the pattern of cognitive decline in MS is a function of the location of demyelinating lesions within the cerebral hemispheric white matter. Finally, we supplement the group study results with a case report of an MS patient who was studied serially with MRI and cognitive testing.

294 citations


Journal Article
TL;DR: The revised Hasegawa's dementia scale (HDS-R), consisting of 9 simple questions with a maximum score of 30, was examined in its usefulness for screening age-associated dementia in a total of 157 subijects and proved to be valid in terms of compatability with the established dementia screening test.
Abstract: Revised Hasegawa's dementia scale (HDS-R), consisting of 9 simple questions with a maximum score of 30, was examined in its usefulness for screening age-associated dementia in a total of 157 subijects: 95 demented patients and 62 non-demented persons. The two groups were age-matched. Cronbach's coefficient alpha was as high as 0.90 in HDS-R. In addition, the coefficient of correlation of each question's score to the total score of other questions in the IHDS-R was significantly high, ranging between 0.79 and 0.40. These findings proved that the HDS-R could satisfy the fundamental prerequisite for dementia screening tests: reliability in terms of internal consistency. Clinical applicability of the HDS-R was confirmed by the following two findings. (a) significant differences were noted between the demented and non-demented groups in each question's score, total mean score and mean score by DS-based severity. (b) Dementia could be most exactly discriminated from non-dementia with sensitivity of 0.90 and specificity of 0.82 at a cutoff point of 20/21 . The coefficient of correlation of the HDS-R to the MMSE was as high as 0.94, proving the HDS-R to be valid in terms of compatability with the established dementia screening test. In conclusion, the HDS-R can screen dementia at the highest conceivable accuracy and efficiency. It may also serve to assess the severity of dementia changing with time and the effect of pharmacotherapy and rehabilitation. Keywords: dementia, screening test, HDS-R, sensitivity, specificity INTRODUCTION Since the primary symptoms of dementia are cognitive decline, various intelligence tests such as the WAIS (Weschesler Adult Intelligence Scale) have f used for its assesment. However the WAIS is not generally able for screening for dementia since it takes too long to administer, and has not been adequately standardize for elderly subject with cognitive changes associated with normal aging. For the purpose of screening for dementia, questions dimild be eat answered key normal elderly persons, but individuals with dementa should find them difficult. Ideally, these should ba a standardized, simple and quick test of cognitive function for routine use by the physcian Many simple scales for assessment of dementia have been deVeloped and are currently in use. Of these, the Mini-Mental State Examination (MMSE) of Folstein et al. (1975) and the Dementia RAM Scale of Blessed et al. (1968) are perhaps the most widely used brief instruments for assessing severity. Hasegawa et al. (1974) developed and standardized a brief dementia screening scale, called the Hasegawa's Dementia Stale (HDS) which comprises 11 questions (Hasegawa 1983). The HDS have been the most widely accepted not only for clinical we in hospitals and elderly nursing home, but also epiderrdolcgxcal surveys in Japan (Hasegawa and hnad, 1989). However, a recent review of the HDS required us to reconsider some questions and study a feasibility for worldwide use. In consequence, we decided to delete the following five questions because they were judged to be obsolete or lacking universality: 1. The place of the subject's birth (since it is impossible to confirm without the presence of the subject's family). 2. The year of the termination of World War II in Japan (since it is not appropriate for international use and not even applicable to Japanese population). 3. The number of days in opte years (since it is very easily answered even by patients with dementia). 4. The name of the present prime minister in Japan (since it is not appropriate for intercultural use). 5. How long have you been here (since it needs advance information from person around the subject or lacks uniformity in answers among among individuals). Instead immediate recall of 3 words, delay recall of 3 words, and list-ratirg fluency were added. The HDS was recontructed in this manner and named the revised HDS (HDS-R). …

233 citations


Journal ArticleDOI
TL;DR: The presence of extrapyramidal signs and behavioral symptoms (agitation and hallucinations) significantly predict faster cognitive decline, which may reflect the effects of neuroleptic medication, the presence of underlying diffuse Lewy body disease, or alterations in biogenic amine systems.
Abstract: Objective: To identify clinical predictors of cognitive decline in Alzheimer's disease. Design: A cohort of patients was followed up longitudinally and the likelihood of arriving at two cognitive end points was assessed using the Cox proportional hazards model and eight explanatory variables. Setting: Subjects were chosen from patients examined for memory loss at two medical centers affiliated with the University of Southern California, Los Angeles. Patients: The sample included 135 patients who met National Institute for Neurological and Communicative Disorders and Stroke—Alzheimer's Disease and Related Disorders Association criteria for probable or definite Alzheimer's disease, had initial Mini-Mental State Examination (MMSE) scores of 14 or greater, and had been seen on at least two occasions. Main Outcome Measures: The time to reach either of two end points, ie, MMSE score of 8 and a decline of six points on the MMSE, was assessed. Results: After controlling for initial severity of dementia (eg, by dividing the sample into mild and moderate dementia subgroups or by using the individually defined end point of a six-point decline on the MMSE), the presence at baseline of extrapyramidal signs (risk-hazard ratio, 10.34; 95% confidence interval, 2.76 to 38.68;P=.0005), agitation (risk-hazard ratio, 2.98; 95% confidence interval, 1.35 to 6.61;P=.007),and hallucinations (risk-hazard ratio, 3.85; 95% confidence interval, 1.35 to 11;P=.01) predicted a shorter time to reach an end point. Conclusions: After controlling for initial severity of dementia, the presence of extrapyramidal signs and behavioral symptoms (agitation and hallucinations) significantly predict faster cognitive decline. These findings may reflect the effects of neuroleptic medication, the presence of underlying diffuse Lewy body disease, or alterations in biogenic amine systems.

202 citations


Journal ArticleDOI
TL;DR: In a community survey, subjects and their informants were asked the same questions about memory and intellectual decline in the subjects, and reports of cognitive decline were correlated with anxiety and depression symptoms and with trait neuroticism.
Abstract: In a community survey, subjects and their informants were asked the same questions about memory and intellectual decline in the subjects. Subjects and informants both commonly reported cognitive decline, although in most cases the decline was not seen as interfering with daily life. However, when responses from subjects and informants were cross-tabulated, agreement was found to be poor. For subjects, reports of cognitive decline were correlated with anxiety and depression symptoms and with trait neuroticism. Subjects' reports were uncorrelated with age and only weakly correlated with cognitive test performance, indicating little validity. By contrast, informants' reports were correlated with the subjects' cognitive test performance and age, but also with the informants' own anxiety and depression symptoms. Although informants' reports have validity, they may also be contaminated by the informants' affective state.

170 citations



Journal ArticleDOI
05 Nov 1994-BMJ
TL;DR: The apolipoprotein e4 allele predisposes to cognitive decline in a general population of elderly men and twenty two per cent of the risk of developing impaired cognitive function in this population may be attributable to the e 4 allele.
Abstract: Objectives - To determine whether polymorphism of apolipoprotein E - notably, the e4 allele - predicts cognitive deterioration in the general population. Design - Population based cohort investigated in 1990 and in 1993. Setting - Zutphen, the Netherlands. Subjects - Representative cohort of 538 Dutch men aged 70-89 at baseline. Main outcome measures - Cognitive function assessed by mini mental state examination, change in cognitive function and incidence of impaired cognitive function at three years. Results - The baseline prevalence of impaired cognitive function (mini mental state examination score ≤ 25) was higher among carriers of the e4 allele compared with men without the allele (41.0% (55) v 31.1% (122) P = 0.03), and this result was still valid after adjustment for age, occupation, smoking, alcohol use, and cardiovascular diseases. The decline in cognitive function at three years was largest in men homozygous for e4 (-2.4 points), intermediate in those heterozygous for e4 (-0.7 points), and lowest in men without e4 (-0.1 points), and it was independent of other risk factors (P = 0.02). The risk of developing impaired cognitive function during follow up was significantly increased in allele carriers compared with non-carriers (27.6% (16/58) v 15.5% (32/207)). The adjusted odds ratio was 2.87 (95% confidence interval 1.29 to 6.42). Twenty two per cent of the risk of developing impaired cognitive function in this population may be attributable to the e4 allele. Conclusions - The apolipoprotein e4 allele predisposes to cognitive decline in a general population of elderly men.

161 citations


Journal ArticleDOI
TL;DR: The results suggest that intellectual function does not markedly decline during the adulthood of patients with schizophrenia, and the course of schizophrenia is more consistent with a static encephalopathy than a dementing disorder.
Abstract: The issue of progressive cognitive decline in patients with schizophrenia has been debated. We performed a cross-sectional study of patients with chronic schizophrenia, aged from 18 to 69 years, in order to address this issue. The patients included in this study passed a rigorous screen for any comorbid condition with an adverse impact on central nervous system function. We assessed intellectual deterioration with a battery of neuropsychological tests known to be sensitive to cognitive impairment in progressive dementia. No evidence of accelerated intellectual decline was found. No significant differences were found between the five age-derived cohorts (18-29, 30-39, 40-49, 50-59, and 60-69 years of age) on the Mini-Mental State Examination, Dementia Rating Scale, or other tests sensitive to dementia. While performance on the Boston Naming Test significantly declined with age, this was mainly due to age rather than duration of illness. However, it is important to note that mean performances on the majority of the tests were abnormal across all cohorts studied. These results suggest that intellectual function does not markedly decline during the adulthood of patients with schizophrenia. The course of schizophrenia is more consistent with a static encephalopathy than a dementing disorder.

148 citations


Journal Article
TL;DR: The association of increased oxygen extraction with decline in some measures of cognitive function suggests that an imbalance in cerebral tissue oxygen supply, which is unrelated to age, contributes to acute cognitive dysfunction after cardiac surgery.
Abstract: BACKGROUND Age is a predictor of cognitive dysfunction after cardiac surgery, but the mechanism is unknown The purpose of our study was to determine whether age-related decrements in cognition are associated with cerebral blood flow (CBF) autoregulation during cardiopulmonary bypass (CPB) METHODS AND RESULTS Cognitive function testing was completed before surgery and before hospital discharge in 215 patients undergoing elective coronary artery bypass grafting (CABG) surgery The battery consisted of seven tests with nine measures designed to evaluate memory, mood changes, and visuomotor speed and function Pressure-flow and metabolic-flow cerebral autoregulation during hypothermic cardiopulmonary bypass were determined using the 133Xe clearance CBF method and radial artery and jugular bulb effluent to calculate cerebral metabolic rate (CMRO2) and cerebral AV difference (C[AV]O2) Pressure-flow autoregulation was tested by using two CBF measurements at stable hypothermia: one at stable mean arterial pressure (MAP) and the second 15 minutes later when MAP had increased or decreased > or = 20% Metabolism-flow autoregulation was tested by varying the temperature (CMRO2) and measuring the coupling of CBF and CMRO2 Individual patient autoregulation was correlated with changes in cognitive measures Cognitive performance declined in 6 of 9 measures after CABG surgery Age predicted cognitive decline in 7 of 9 measures; short-term memory showed the greatest effect of age Pressure-flow autoregulation during hypothermic CPB showed a small but significant (P < 0001) effect of pressure on CBF There was no effect of age on the slope of CBF response to changes in MAP (pressure-flow autoregulation) There was a major effect of temperature on CBF during CPB (P < 0001) Coupling CBF and CMRO2 with changing temperature was unaffected by age Changes in cognition were not associated with measures of cerebral autoregulation However, increasing C(AV)O2 is associated with cognitive deficits in 5 of 9 measures; these associations were independent of age CONCLUSIONS Increased age predisposes to impaired cognition after cardiac surgery This decline in cognitive function in the elderly is not associated with age-related changes in cerebral blood flow autoregulation The association of increased oxygen extraction with decline in some measures of cognitive function suggests that an imbalance in cerebral tissue oxygen supply, which is unrelated to age, contributes to acute cognitive dysfunction after cardiac surgery Cognitive dysfunction after CPB in the elderly cannot be explained by impaired CBF autoregulation

Journal ArticleDOI
TL;DR: Indirect evidence suggests that estrogen interacts with NGF-related systems and that changes in circulating levels of estrogen can contribute to age-related changes in hippocampal levels of NGF.
Abstract: Estrogen replacement can significantly affect the expression of ChAT and NGF receptors in specific basal forebrain cholinergic neurons The time-course of the effects is consistent with a direct up-regulation of ChAT followed by either direct or indirect down-regulation of p75NGFR and trkA NGF receptors, possibly due to increased cholinergic activity in the hippocampal formation and cortex and a decrease in hippocampal levels of NGF Current evidence suggests ChAT, p75NGFR, trkA, and NGF all play a role in regulating cholinergic function in the hippocampal formation and cortex In addition, all have been implicated in the maintenance of normal learning and memory processes as well as in changes in cognitive function associated with aging and with neurodegenerative disease It is possible that estrogen may affect cognitive function via effects on NGF-related systems and basal forebrain cholinergic neurons Effects of estrogen on cognitive function have been reported, as has some preliminary evidence for beneficial effects of estrogen in decreasing the prevalence of and reducing some cognitive deficits associated with Alzheimer's disease Whether these effects are related to effects on NGF-related systems or basal forebrain cholinergic neurons is currently unknown Indirect evidence suggests that estrogen interacts with NGF-related systems and that changes in circulating levels of estrogen can contribute to age-related changes in hippocampal levels of NGF These findings have important implications for consideration of estrogen replacement therapy in pre- and post-menopausal women Further studies examining effects of different regimens of estrogen replacement as well as estrogen combined with progesterone on NGF and basal forebrain cholinergic neurons in young and aged animals are required Prospective studies correlating aging and estrogen replacement with numbers of basal forebrain cholinergic neurons and hippocampal and cortical levels of NGF also need to be performed to better assess the potential benefits of estrogen replacement in reducing age- and disease-related cognitive decline

Journal ArticleDOI
01 May 1994-Dementia
TL;DR: There is now an urgent need for further research on risk factors for VAD and on factors related to dementia in subjects with cerebrovascular disorders.
Abstract: In recent years, interest in vascular causes of dementia has increased and it has been proposed that vascular dementia (VAD) may be more common than previously supposed. This may have important implications, because VAD at present may be more amenable to prevention and treatment than Alzheimer's disease (AD). Several vascular factors have been related to cognitive decline and dementia in the elderly, including stroke and white matter disease. However, while numerous case-control studies have been concerned with the risk factors for AD, studies on risk factors for VADs are rare. The problems inherent in the diagnostic criteria make it difficult to interpret the results from the few studies that have been performed. Generally, risk factors for multi-infarct dementia are supposed to be the same as those for stroke, and include hypertension, diabetes mellitus, advanced age, male sex, smoking and cardiac diseases. White matter dementia has mainly been related to hypertension. Recent research suggests that vascular factors may also be important in AD, especially in the late-onset type. In stroke patients, dementia has been associated with higher age, less formal education, cerebral atrophy, left-sided or bilateral infarcts, volume of macroscopic infarcts, bilateral symptoms, previous stroke and white matter lesions. The pathogenetic mechanism through which these factors cause dementia is still not clear. Furthermore, it is not known if risk factors for VAD differ from those found in stroke patients. There is now an urgent need for further research on risk factors for VAD and on factors related to dementia in subjects with cerebrovascular disorders.

Journal ArticleDOI
TL;DR: In view of the lack of a proven agent to limit or halt the progression of dementia in the elderly, idebenone may warrant consideration in patients with mild cognitive dysfunction on the basis of preliminary evidence of predominantly mild improvement of functional status in some patients and good tolerability.
Abstract: Idebenone is a benzoquinone compound which has been investigated in elderly patients with dementia. Its precise mechanism(s) of action remains unknown, but in vitro and in vivo studies suggest the drug may diminish nerve cell damage due to ischaemia, correct neurotransmitter defects and/or cerebral metabolism and facilitate memory and learning. In the small number of studies available for evaluation, idebenone was generally superior to placebo and comparable with bifemelane, oxiracetam and nebracetam on the basis of a number of objective and subjective tests and rating scales in patients with mild to moderate cognitive decline. Clinical trial results indicate that patients with mild dementia seem more likely to respond than those with greater functional decline. The degree of benefit conferred by idebenone is often difficult to determine, but in those who respond, improvement is generally mild to moderate. Therapy with idebenone appears well tolerated for up to 2 years, and no changes in vital signs or laboratory values have been seen in clinical trials. In view of the lack of a proven agent to limit or halt the progression of dementia in the elderly, idebenone may warrant consideration in patients with mild cognitive dysfunction on the basis of preliminary evidence of predominantly mild improvement of functional status in some patients and good tolerability. However, further well designed studies, including comparisons with newer and commonly used agents, such as tacrine, are required to better define the role of idebenone in this complex area of treatment.

Journal ArticleDOI
TL;DR: Variation in causes for patients with Alzheimer disease and other dementing illnesses enrolled in a population‐based Alzheimer disease patient registry is described and the variation in causes by the level of cognitive impairment before death in probable AD cases is described.
Abstract: OBJECTIVE: To describe causes of death for patients with Alzheimer disease (AD) and other dementing illnesses enrolled in a population-based Alzheimer disease patient registry (ADPR) and to describe the variation in causes by the level of cognitive impairment before death in probable AD cases. SETTING: The ADPR enrolls and diagnoses newly recognized potential dementia cases occurring in a large, stable health maintenance organization. To date, 654 cases have been enrolled and followed annually to monitor cognitive decline and verify initial diagnosis. DESIGN: Longitudinal descriptive study. PATIENTS: ADPR enrollees who have died. MEASUREMENTS: Death certificates were obtained for all who died (total n = 104, probable AD = 55); reported causes of death were reviewed by a physician to determine the underlying cause. AD patients were categorized according to their Mini-Mental State Exam score (cognitive impairment) within 12 months of death as (a) mildly (21+), (b) moderately (15–20), or (c) severely (0–14) impaired, and underlying cause and all reported causes of death for each group were tabulated. MAIN RESULTS: Among probable AD patients, pneumonia and AD were most often recorded on death certificates when cognitive impairment within the year prior to death had reached the severe level; heart disease, stroke, and other common causes of death predominated in AD patients who were less cognitively impaired. CONCLUSIONS: When AD cases were followed from first diagnosis to death, the causes of death varied by level of cognitive impairment. Illnesses potentially amenable to treatment caused death at all levels of disease, but more so early in the course of AD. Cognitive impairment may make patients less able to recognize and report symptoms of medical problems, thereby complicating efforts to intervene.

Journal ArticleDOI
TL;DR: The influence of educational background on test performance is most evident in individuals with less education, and commonly used dementia screening tests may be unfair to poorly educated individuals, especially women and rural residents.
Abstract: Objective: To examine the relation between performance on a dementia screening test and the demographic variables of age, education, gender, and urban vs rural residency. Design: Community survey with cluster sampling. Setting: One urban and one rural community from each of four geographic regions in Taiwan, Republic of China. Participants: A total of 5265 nondemented individuals approximately equally divided between men and women and between urban and rural residency with a range in age from 41 to 88 years and in education from 0 to 20 years. Main Outcome Measure: Score on a Chinese adaptation of the Mini-Mental State Examination. Results: Lower test scores were associated with older age and less education. The decrease in score with age was faster among participants who had never attended school. Better performance by men and by urban residents was found only among participants with fewer than 6 years of schooling. In this group, the magnitudes of sex and residency differences were comparable among those subjects aged 41 to 64 years and those aged 65 to 88 years. Women who had never worked outside of the home performed poorer than those who had worked outside of the home. Conclusions: The influence of educational background on test performance is most evident in individuals with less education. Commonly used dementia screening tests may be unfair to poorly educated individuals, especially women and rural residents. Efforts should be made to develop ecologically relevant cognitive tests for the intended study populations. To help distinguish test bias from different rates of cognitive decline, the study populations should include individuals in predementia age ranges.

Journal ArticleDOI
TL;DR: In this article, the authors examined hypotheses that might explain the relationship between cognitive function and performance in the work environment and concluded that there is not a reliable correlation between age and work performance, and that older adults have enhanced opportunities for environmental supports in the workplace which can compensate for cognitive decline.
Abstract: There are well documented declines in cognitive function with age, and there are also reliable relations between cognitive function and performance in the work environment. Despite these relations, there is not a reliable correlation between age and work performance. This article examines hypotheses that might explain this paradox. Hypotheses discussed include (a) older adults have jobs characterized by maintenance functions and rarely must learn new information, (b) experience protects older adults from decline in highly practiced cognitive tasks, (c) complex knowledge structures increase with age and compensate for decline in component processes of cognition, and (d) older adults have enhanced opportunities for environmental supports in the workplace which can compensate for cognitive decline. Implications of age‐related cognitive declines for training and human‐factors issues in the work environment are discussed.

Journal ArticleDOI
TL;DR: White matter hyperintensities seem not to be related to the degree of global cognitive decline in dementia and whether it plays a causative role in the development of dementia symptoms needs to be more thoroughly investigated.

Journal ArticleDOI
TL;DR: The results suggest that short-term potentiation of NMDA-mediated glutamatergic transmission may not prove useful in the symptomatic treatment of Alzheimer dementia.
Abstract: SummaryDegeneration of cortical glutamatergic projections may contribute to the cognitive decline in Alzheimer disease (AD). To evaluate whether 1glutamate system stimulation might confer symptomatic benefit, we administered D-cycloserine, a putative partial indirect agonist at certain N-methyl- D-a

Journal ArticleDOI
TL;DR: The reversible cognitive deterioration indicates a clear CNS effect during the IFN-α treatment, and a clear difference in the performance profiles of the placebo and the IFNs treated patient groups was detected.
Abstract: The cognitive effects of high-dose human leukocyte α-interferon (IFN-α) treatment were evaluated among 15 patients with the newly diagnosed spinal form of amyotrophic lateral sclerosis (ALS). To confirm the earlier findings showing reversible effects on cognitive performance and to exclude confounding effects, a randomized blinded placebo controlled study was conducted. Twelve patients with continuous intravenous IFN-α-infusion treatment over five days and 3 placebo control patients were neuropsychologically evaluated. The neuropschological examination included tests of intelligence, memory, complex mental processing, visuoconstructional skills, writing, and calculation. A clear difference in the performance profiles of the placebo and the IFN-α-treated patient groups was detected: The IFN-α group showed significant deterioration during treatment in the digit span backwards task, logical verbal memory task, calculation ability, and writing time, while improvement was seen after treatment. Concomitant fever did not explain the findings. In the placebo group an improvement indicating a learning effect in the three consecutive measurements was found. The reversible cognitive deterioration indicates a clear CNS effect during the IFN-α treatment.

Journal ArticleDOI
TL;DR: The clinical efficacy and the tolerability of alpha-glycerophosphocholine, a drug able to provide high levels of choline for the nervous cells of the brain and to protect their cell walls, have been tested in a clinical open multicenter trial on 2044 patients suffering from recent stroke or transient ischemic attacks.
Abstract: The clinical efficacy and the tolerability of alpha-glycerophosphocholine (alpha-GPC), a drug able to provide high levels of choline for the nervous cells of the brain and to protect their cell walls, have been tested in a clinical open multicenter trial on 2044 patients suffering from recent stroke or transient ischemic attacks. alpha-GPC was administered after the attack at the daily dose of 1000 mg im for 28 days and orally at the dose of 400 mg tid during the following 5 months after the first phase. The evaluation of the efficacy on the psychic recovery was done by the Mathew Scale (MS) during the period of im drug administration, and using the Mini Mental State Test (MMST), the Crichton Rating Scale (CRS), and the Global Deterioration Scale (GDS) during the following period of oral administration. The MS mean increased 15.9 points in 28 days in a statistically significant way (p < 0.001) from 58.7 to 74.6. At the end of the 5 month oral administration, the CRS mean significantly decreased 4.3 points, from 20.2 to 15.9 (p < 0.001); the MMST mean significantly increased (p < 0.001) from 21 to 24.3 at the end of the trial, reaching the "normality" score at the 3rd month assessment. The GDS score at the end of the trial corresponded to "no cognitive decline" or "forgetfulness" in 71% of the patients. Adverse events were complained of by 44 patients (2.14%); in 14 (0.7%) the investigator preferred to discontinue therapy. The most frequent complaints were heartburn (0.7%), nausea-vomit (0.5%), insomnia-excitation (0.4%), and headache (0.2%). The trial confirms the therapeutic role of alpha-GPC on the cognitive recovery of patients with acute stroke or TIA, and the low percentage of adverse events confirms its excellent tolerability.

Journal ArticleDOI
TL;DR: In this article, three domains of cognition (cognitive slowing, working memory, and new learning ability) are reviewed, based on neuropsychological findings, three aspects of biological aging (general neuronal efficacy, frontal lobe function, medial temporal lobe function) mediate the three respective domains of cognitive changes.

Journal ArticleDOI
TL;DR: It is recommended that respondents in community surveys, including the elderly, be informed that they can decline to answer any question, and that interviewers be trained in how to respond to the few who will be distressed by the experience.
Abstract: In a community survey of 873 persons aged 70 years or over, focusing on dementia, cognitive decline, depression, and current life circumstances, we included an enquiry into the emotional impact of the interview. A large majority reported at the end of the interview that it had no adverse effect on their emotional state. About 4% reported that it made them distressed, 1% that it depressed them, and 2% that it had intruded on their privacy. By contrast, 52% said it had made them feel good about themselves. Distress seemed to be largely related to performing poorly on cognitive tests. There is no information on the duration of these effects in the period following the interview. It is recommended that respondents in community surveys, including the elderly, be informed that they can decline to answer any question, and that interviewers be trained in how to respond to the few who will be distressed by the experience.

Journal ArticleDOI
TL;DR: An organized, systematic approach with early diagnosis and treatment of delirium in elderly hospitalized patients may prove to be life-saving in many patients.
Abstract: BACKGROUND As many as one third of elderly hospitalized patients become delirious, and most do not fully recover. Delirium may impart a higher mortality rate and may be a marker for future cognitive decline. OBJECTIVE To review the clinical features, etiology, diagnosis, and management of delirium in elderly hospitalized patients. SUMMARY Delirium can be caused by primary intracranial disease, systemic diseases, withdrawal from alcohol or sedative hypnotic agents, or drug intoxication, the most common cause. Because delirium may present with diverse clinical features, physicians should suspect it in any elderly patient with a change in mental status, personality, or behavior. Bedside screening tools may help distinguish delirium from dementia and psychosis. Causative factors should be sought and removed or treated. Anticholinergic drugs are the worst offenders, but all drugs are suspect and should be discontinued or reduced in dosage. If a sedative is needed, haloperidol is the drug of choice. Because of the prevalence and seriousness of alcohol withdrawal, all delirious patients should receive intravenous thiamine to reduce the risk of Wernicke9s encephalopathy. CONCLUSIONS An organized, systematic approach with early diagnosis and treatment may prove to be life-saving in many patients.


Journal ArticleDOI
TL;DR: Since synapse loss correlates best with cognitive decline in AD, the model of synapse formation and elimination is presented, and recent exciting findings concerning the involvement of thrombin-like activity in synapse elimination are discussed.

Journal ArticleDOI
TL;DR: It is hypothesized that the cumulative effects of infarcts were synergistic, that is, the posterior cortical infarCTs elicited frontal features that would not be expected from a simple sum of these lesions' effects.
Abstract: Objective: The goal of this study was to characterize the cumulative effects of multiple strokes on cognition. Design: We conducted a prospective, longitudinal case study with neuropsychological, neurological, and radiological evaluations. Setting: Research was conducted at the Boston (Mass) Veterans Administration Medical Center, Neurology Service, on successive inpatient hospital admissions. Patient: We followed up a 66-year-old right-handed man with multiple subcortical lacunae during a 3.5-year period during which he suffered two additional cortical infarctions. Main Outcome Measures: Each evaluation included approximately 3 hours of neuropsychological testing spanning a range of cognitive domains (attention, language, memory, visuospatial functions, response inhibition, and mental flexibility), full neurological examination, and computed tomographic scan. Results: The patient's stepwise cognitive decline was characterized by unexpected exacerbation of "frontal" neurobehavioral features following the occurrence of two posterior cortical lesions. At initial evaluation, the computed tomographic scan showed bilateral subcortical lacunae in basal ganglia and periventricular white matter, and symptoms included dysarthria and perseveration. The second evaluation, following a left posterior parietal lesion, revealed a range of new frontal features, including impulsivity, pull-to-stimulus, and difficulty shifting set. Following a subsequent right occipital infarct, further frontal lobe impairments emerged: forced grasp reflex and incontinence. Conclusions: We hypothesize that the cumulative effects of infarcts were synergistic. That is, the posterior cortical infarcts elicited frontal features that would not be expected from a simple sum of these lesions' effects.

Journal ArticleDOI
TL;DR: It is shown that the indirect activation of glutamatergic neurotransmission by agonists of the glycine site or the restoration of the age-related deficit of receptor density by several nootropics is the most promising approach to improve cognition by compensating the NMDA receptor deficits in aging.

Journal ArticleDOI
TL;DR: The studies in mice and Syrian hamsters aim at the question whether the effects of selegiline reported in the rat can be generalized to other species and suggest a protective effect of a chronic treatment with seLegiline against age-related cognitive and physical decline.

Book ChapterDOI
TL;DR: The most promising approaches to improve cognition by compensating the NMDA-receptor deficits in aging are the indirect activation of glutamatergic neurotransmission by agonists of the glycine site or the restoration of the age-related deficit of receptor density by several nootropics.
Abstract: Age-related changes of N-methyl-D-aspartate (NMDA) receptors have been found in cortical areas and in the hippocampus of many species. On the basis of a variety of experimental observations it has been suggested that the decrease of NMDA-receptor density might be one of the causative factors of the cognitive decline with aging. Based on these findings several strategies have been developed to improve cognition by compensating the NMDA-receptor deficits in aging. The most promising approaches are the indirect activation of glutamatergic neurotransmission by agonists of the glycine site or the restoration of the age-related deficit of receptor density by several nootropics.