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Showing papers on "Cognitive decline published in 1999"


Journal ArticleDOI
TL;DR: Whether a global measure of social disengagement was associated with incident cognitive impairment in a large cohort of community-dwelling elderly persons followed for 12 years is determined.
Abstract: Social engagement, defined as the maintenance of many social connections and a high level of participation in social activities, has been thought to prevent cognitive decline in elderly persons. In...

913 citations


Journal ArticleDOI
TL;DR: There was a relationship between changes in intellectually related activities and changes in cognitive functioning and these results are consistent with the hypothesis that intellectually engaging activities serve to buffer individuals against decline.
Abstract: Data from the Victoria Longitudinal Study were used to examine the hypothesis that maintaining intellectual engagement through participation in everyday activities buffers individuals against cognitive decline in later life. The sample consisted of 250 middle-aged and older adults tested 3 times over 6 years. Structural equation modeling techniques were used to examine the relationships among changes in lifestyle variables and an array of cognitive variables. There was a relationship between changes in intellectually related activities and changes in cognitive functioning. These results are consistent with the hypothesis that intellectually engaging activities serve to buffer individuals against decline. However, an alternative model suggested the findings were also consistent with the hypothesis that high-ability individuals lead intellectually active lives until cognitive decline in old age limits their activities.

878 citations


Journal ArticleDOI
TL;DR: A substantial portion of ARDS survivors exhibit impaired health status and cognitive sequelae which may be due to hypoxemia, emboli, inflammation, drug toxicity, and/or other etiologies one year after ARDS.
Abstract: Acute respiratory distress syndrome (ARDS) is a disease of acute respiratory failure manifested by severe hypoxemia with a high mortality rate. Previous outcome studies of ARDS have assessed survival and/or pulmonary function as the primary outcome variables. Cognitive or psychological outcomes following ARDS have not been described, despite the possibility that ARDS patients are at risk for brain injury through hypoxemia or other mechanisms. In the current study 55 consecutive ARDS survivors completed a battery of neuropsychological tests and questionnaires regarding health status, cognitive and psychological outcomes at the time of hospital discharge and 1 yr after onset of ARDS. At hospital discharge, 100% (55 of 55) of survivors exhibited cognitive and affective impairments, as well as problems with health status which affected their quality of life. At 1 yr after ARDS, 17 of 55 (30%) patients still exhibited generalized cognitive decline. Forty-three of 55 (78%) patients had all or at least one of the following: impaired memory, attention, concentration and/or decreased mental processing speed. One year after ARDS a substantial portion of ARDS survivors exhibit impaired health status and cognitive sequelae which may be due to hypoxemia, emboli, inflammation, drug toxicity, and/or other etiologies.

604 citations


Journal ArticleDOI
TL;DR: The evidence for an association between cognitive impairment or dementia and the presence of Type 2 diabetes mellitus is examined and potential mechanisms for such an association are sought.
Abstract: Summary Aims We set out to examine the evidence for an association between cognitive impairment or dementia and the presence of Type 2 diabetes mellitus (DM). We also sought evidence of potential mechanisms for such an association. Methods A literature search of three databases was performed and the reference lists of the papers so identified were examined, using English language papers only. Results We found evidence of cross-sectional and prospective associations between Type 2 DM and cognitive impairment, probably both for memory and executive function. There is also evidence for an elevated risk of both vascular dementia and Alzheimer’s disease in Type 2 DM albeit with strong interaction of other factors such as hypertension, dyslipidaemia and apolipoprotein E phenotype. Both vascular and non-vascular factors are likely to play a role in dementia in diabetes. Conclusions Current classification structures for dementia may not be adequate in diabetes, where mixed pathogenesis is likely. Further research into the mechanisms of cognitive impairment in Type 2 DM may allow us to challenge the concept of dementia, at least in these patients, as an irremediable disease. Diabet. Med. 16, 93–112 (1999)

550 citations


Journal ArticleDOI
TL;DR: The findings of this study suggest that memory complaints are a relatively strong predictor of incident Alzheimer's disease in older persons in whom cognitive impairment is not yet apparent, and suggest that older persons may be aware of a decline in cognition at a time when mental status tests are still unable to detect a decline from premorbid functioning.
Abstract: OBJECTIVE: Results of previous studies suggest that memory complaints may predict cognitive decline and dementia among elderly people in whom cognitive impairment is already apparent. However, cognitive decline is often a gradual process, and elderly people may notice that their memory deteriorates before mental status tests are able to detect any change in cognitive functioning. Therefore, the authors hypothesized that memory complaints would predict incident Alzheimer’s disease in elderly subjects with no signs of cognitive impairment. METHOD: In the community-based Amsterdam Study of the Elderly, a sample of 3,778 nondemented persons, 65 to 84 years old, was selected and divided into two cognitive categories: normal (Mini-Mental State scores of 26–30) and borderline and impaired (Mini-Mental State scores less than 26). At baseline, the presence or absence of memory complaints was assessed. At follow-up, incident cases of Alzheimer’s disease were diagnosed in a two-step procedure. RESULTS: After an aver...

475 citations


Journal ArticleDOI
07 Jul 1999-JAMA
TL;DR: Most healthy elderly people did not experience cognitive decline and measures of subclinical CVD were modest predictors of cognitive decline, while high levels of atherosclerosis increased cognitive decline independently of APOE genotype.
Abstract: ContextCognitive decline in elderly persons is often an early predictor of dementia. Subclinical cardiovascular disease (CVD) and diabetes mellitus may contribute to substantial decline in cognitive function in the elderly. These risks may be modified by gene-environment interactions between apolipoprotein E (APOE) genotype and CVD risk factors or subclinical CVD.ObjectivesTo examine the association between subclinical CVD and decline in cognitive functioning in the elderly and to examine effect modification by the APOE genotype of the association between subclinical disease and cognitive decline.DesignThe Cardiovascular Health Study, a population-based, prospective cohort study.Setting and PopulationA total of 5888 randomly selected Medicare-eligible participants from Sacramento County, California; Forsyth County, North Carolina; Washington County, Maryland; and Pittsburgh, Pa, aged 65 years or older, who were recruited in 1989-1990 (n = 5201) and in 1992-1993 (n = 687) and who were followed up for 7 and 5 years, respectively.Main Outcome MeasuresChange over time in scores on the Modified Mini-Mental State Examination and the Digit Symbol Substitution Test as a function of APOE genotype, subclinical CVD, and diabetes mellitus.ResultsSeventy percent of participants had no significant decline on the Modified Mini-Mental State Examination. Systolic blood pressure, the ankle-arm brachial index, atherosclerosis of the internal carotid artery, diabetes mellitus, and several diagnoses of prevalent CVD were significantly associated with declines in scores on the Modified Mini-Mental State Examination and the Digit Symbol Substitution Test. The rate of cognitive decline associated with peripheral vascular disease, atherosclerosis of the common and internal carotid arteries, or diabetes mellitus was increased by the presence of any APOE ∊4 allele.ConclusionsMost healthy elderly people did not experience cognitive decline. Measures of subclinical CVD were modest predictors of cognitive decline. Those with any APOE ∊4 allele in combination with atherosclerosis, peripheral vascular disease, or diabetes mellitus were at substantially higher risk of cognitive decline than those without the APOE ∊4 allele or subclinical CVD. High levels of atherosclerosis increased cognitive decline independently of APOE genotype.

452 citations


Journal ArticleDOI
TL;DR: It is suggested that R6/2 mice provide not only a model for studying cognitive and motor changes in trinucleotide repeat disorders, but also a framework within which the functional efficacy of therapeutic strategies aimed at treating such diseases can be tested.
Abstract: Cognitive decline is apparent in the early stages of Huntington's disease and progressively worsens throughout the course of the disease. Expression of the human Huntington's disease mutation in mice (R6/2 line) causes a progressive neurological phenotype with motor symptoms resembling those seen in Huntington's disease. Here we describe the cognitive performance of R6/2 mice using four different tests (Morris water maze, visual cliff avoidance, two-choice swim tank, and T-maze). Behavioral testing was performed on R6/2 transgenic mice and their wild-type littermates between 3 and 14.5 weeks of age, using separate groups of mice for each test. R6/2 mice did not show an overt motor phenotype until approximately 8 weeks of age. However, between 3.5 and 8 weeks of age, R6/2 mice displayed progressive deterioration in specific aspects of learning in the Morris water maze, visual cliff, two-choice swim tank, and T-maze tasks. The age of onset and progression of the deficits in the individual tasks differed depending on the particular task demands. Thus, as seen in humans with Huntington's disease, R6/2 mice develop progressive learning impairments on cognitive tasks sensitive to frontostriatal and hippocampal function. We suggest that R6/2 mice provide not only a model for studying cognitive and motor changes in trinucleotide repeat disorders, but also a framework within which the functional efficacy of therapeutic strategies aimed at treating such diseases can be tested.

418 citations


Journal ArticleDOI
TL;DR: A partial but prolonged energy impairment induced by 3NP is sufficient to replicate most of the clinical and pathophysiological hallmarks of HD, including spontaneous choreiform and dystonic movements, frontal-type cognitive deficits, and progressive heterogeneous striatal degeneration at least partially by apoptosis.

411 citations


Journal ArticleDOI
TL;DR: In individuals with high blood pressure, cognitive decline occurred in a relatively short time period and the risk was highest in untreated hypertensive patients.
Abstract: Objective: To examine whether baseline high blood pressure and antihypertensive treatment predicts cognitive decline in elderly individuals. Methods: A longitudinal population-based study of elderly individuals (n = 1,373) in Nantes (western France) was undertaken. Individuals 59 to 71 years of age were selected from electoral rolls. High blood pressure at baseline was defined as systolic blood pressure ≥ 160 mm Hg or diastolic blood pressure ≥ 95 mm Hg. Cognitive decline was defined as a drop of 4 points or more on the Mini-Mental State Examination between baseline and the 4-year assessment. Results: There is an association between high blood pressure at baseline and cognitive decline at the 4-year assessment (odds ratio, 2.8; 95% CI, 1.6 to 5.0). In participants with high blood pressure, the risk of cognitive decline was 4.3 (95% CI, 2.1 to 8.8) in those without antihypertensive therapy and 1.9 (95% CI, 0.8 to 4.4) in those being treated. In participants with high blood pressure both at baseline and at the 2-year assessment, the risk for untreated participants was 6.0 (95% CI, 2.4 to 15.0) compared with 1.3 (95% CI, 0.3 to 4.9) in treated participants. Conclusions: High blood pressure was associated with cognitive decline. In individuals with high blood pressure, cognitive decline occurred in a relatively short time period and the risk was highest in untreated hypertensive patients.

373 citations


Journal ArticleDOI
TL;DR: Depressive symptoms in older women are associated with both poor cognitive function and subsequent cognitive decline, and Mechanisms underlying the association between these 2 common conditions need further exploration.
Abstract: Background The association between depressive disorders and subsequent cognitive decline is controversial. We tested the hypothesis that elderly women (aged 65 years and older) without dementia but with depressive symptoms have worse cognitive function and greater cognitive decline than women with few or no symptoms. Methods As part of an ongoing prospective study, we evaluated 5781 elderly, mostly white, community-dwelling women. Women completed the Geriatric Depression Scale short form. Three cognitive tests—Trails B, Digit Symbol, and a modified Mini-Mental State Examination—were administered at baseline and approximately 4 years later. Baseline, follow-up, and change scores for the cognitive tests were analyzed by analysis of covariance and Kruskal-Wallis analysis; the odds of cognitive deterioration (≥3-point decline on the modified Mini-Mental State Examination) were determined by logistic regression. Results At baseline, 211 (3.6%) of the women had 6 or more depressive symptoms. Only 16 (7.6%) of these women were receiving antidepressant medication. Increasing symptoms of depression were associated with worse performance at baseline and follow-up on all 3 tests of cognitive function ( P P Conclusions Depressive symptoms in older women are associated with both poor cognitive function and subsequent cognitive decline. Mechanisms underlying the association between these 2 common conditions need further exploration.

368 citations


Journal ArticleDOI
TL;DR: Rate of global cerebral volume loss correlated strongly with rate of change in Mini-Mental State Examination scores (r = 0.80, p < 0.001), implying clinical relevance to this marker of progression.
Abstract: Twenty-nine untreated patients diagnosed with probable AD and 15 control patients underwent two or more clinical and volumetric MRI assessments with intervals ranging from 5 months to 6 years The change in global cerebral volume for an individual was calculated by a novel method of registration and subtraction of serial scans Rate of global cerebral volume loss correlated strongly with rate of change in Mini-Mental State Examination scores (r = 080, p < 0001), implying clinical relevance to this marker of progression

Journal ArticleDOI
TL;DR: Psychometric intelligence of patients with a longer duration of refractory TLE were most severely impaired, suggesting that epilepsy related noxious events and agents exhaust the compensatory capacity of brain functions.
Abstract: OBJECTIVE—Intractable epilepsy is related to various transient and chronic brain electric and neurochemical disturbances. There is increasing evidence that chronic epilepsy induces secondary neuronal metabolic and structural decline. However, there is no convincing evidence that the cognitive abilities of patients deteriorate with increasing duration of intractable epilepsy. METHODS—To examine whether duration of refractory temporal lobe epilepsy (TLE) is related to generalised cognitive impairment, psychometric intelligence based on the full scale intelligence quotient (FSIQ, WAIS-R) was determined in 209 patients with unilateral TLE. For analyses of variance (ANOVA) patients were grouped into three categories: 30 years of refractory TLE. RESULTS—An ANOVA and a multiple regression analysis showed that duration of TLE affects FSIQ. Patients with >30 years of TLE performed worse than patients with 15 or 30 years of TLE. The factors side of seizure origin and type of lesion on MRI did not reach significance. A second ANOVA including education as factor showed that in patients with higher educational attainment, the mean FSIQ was stable for a longer duration of TLE than in less educated patients. Retesting 6 months after anterior temporal lobectomy seizure free patients (n=85 of 127) had an higher FSIQ but showed a similar duration effect before and after anterior temporal lobectomy. The variables age at epilepsy onset, education, frequency of interictal epileptiform discharges, frequency of habitual and generalised seizures, serum concentration of antiepileptic drugs, and polypharmacy were statistically controlled. CONCLUSIONS—Psychometric intelligence of patients with a longer duration of refractory TLE were most severely impaired. Consequently, refractory TLE seems to be associated with slow but ongoing cognitive deterioration. It is assumed that epilepsy related noxious events and agents exhaust the compensatory capacity of brain functions. However, as in dementia and Alzheimer's disease, higher educational attainment as an indicator of higher brain reserve might delay the cognitive decline.

Journal ArticleDOI
TL;DR: Unexplained olfactory dysfunction in the presence of one or more APOE-e4 alleles is associated with a high risk of cognitive decline and Cross-Cultural Smell Identification Test classifies people with cognitive decline correctly to a greater degree than a global cognitive test.
Abstract: Objective: To determine whether olfactory status predicts cognitive decline (CD) over a 2-year follow-up period. Methods: The authors enrolled individuals in a community-based longitudinal study of memory and aging in the Japanese–American community in King County, WA, between 1992 and 1994. At baseline they screened 1,985 persons using the Cognitive Abilities Screening Instrument (CASI) and the 12-item Cross-Cultural Smell Identification Test (CC-SIT). Of these 1,985 people, 1,836 were found not to be demented. Two years later the authors rescreened 1,604 participants with the CASI. They defined CD as a 2-year loss of ≥5.15 points/100 on the CASI. They genotyped 69% of the 1,604 people completing both examinations for apolipoprotein E (apoE). Results: After adjusting for age, CASI score at baseline, education, smoking, sex, and follow-up time, the authors determined an odds ratio (OR) for CD of 0.90 (95% CI, 0.84 to 0.97) for an increase in each correct point on the CC-SIT (range, 0 to 12). Compared with normosmics, the OR for persons with impaired olfaction (microsmics) was 1.25 (95% CI, 0.83 to 1.89) and for anosmics the OR was 1.92 (95% CI, 1.06 to 3.47). Persons who were anosmic at baseline and who had at least one APOE-e4 allele had 4.9 times the risk of CD (95% CI, 1.6 to 14.9) compared with normosmics without the e4 allele. The estimated relative risk among women was 9.7 (95% CI, 1.3 to 70.4), and for men the risk was 3.2 (95% CI, 0.8 to 12.6). Receiver operating characteristic (ROC) curves showed that although the area under the curve (AUC) for baseline CASI was only 0.51, the AUC for CC-SIT alone was 0.62. Adding CC-SIT to the ROC model with CASI improved the AUC curve from 0.51 to 0.62. Conclusions: Unexplained olfactory dysfunction in the presence of one or more APOE-e4 alleles is associated with a high risk of cognitive decline. Cross-Cultural Smell Identification Test classifies people with cognitive decline correctly to a greater degree than a global cognitive test.

Journal ArticleDOI
03 Feb 1999-JAMA
TL;DR: The findings do not suggest a linear association of BP with cognitive decline, but they are consistent with a more complex relationship between BP and cognition than previously appreciated.
Abstract: ContextPrevious studies raise the possibility that blood pressure (BP) in middle age predicts later cognitive decline.ObjectiveTo examine prospectively the relationship of BP with level of and change in cognitive function in the elderly.DesignLongitudinal, population-based study comprising subjects enrolled in the East Boston component of the Established Populations for the Epidemiologic Study of the Elderly (EPESE) (1982-1983) and the Hypertension Detection and Follow-Up Program (HDFP) (1973-1974).SettingEast Boston, Mass.ParticipantsOf the 3657 participants in the EPESE with baseline BP measurements, 2068 also participated in the HDFP. Subjects were aged 65 to 102 years at baseline in the EPESE and had mental status and memory assessed at baseline and 3 and 6 years.Main Outcome MeasuresNumbers of errors on the Short Portable Mental Status Questionnaire and the East Boston Memory Test and rates of change in these numbers of errors. Subjects had BP measured both at baseline in the EPESE and 9 years before, as part of the HDFP.ResultsIn analyses adjusted for age, sex, and education, there was no strong linear association between BP and cognition. The associations found were fairly small in magnitude, and varied according to which test was used to measure cognition. There was little evidence for an effect of BP on change in cognitive function with either test, or for an effect on level of function on the memory test. In analyses of level of mental status questionnaire performance, however, elevated systolic BP (≥160 mm Hg) 9 years before baseline was associated with a 14% (95% confidence interval [CI], 4%-25%) increase in error rate, relative to the referent (130-139 mm Hg). Baseline systolic BP had a U-shaped association with the number of errors; error rates were 9% higher compared with the referent group among those with systolic BP lower than 130 mm Hg (95% CI, 1%-17%) and 7% greater (95% CI, 0%-15%) among those with elevated systolic BP. Diastolic BP 9 years before baseline also had a U-shaped association with errors on the mental status questionnaire.ConclusionThe findings do not suggest a linear association of BP with cognitive decline, but they are consistent with a more complex relationship between BP and cognition than previously appreciated.

Journal ArticleDOI
TL;DR: A relation between homocysteine and reduced cognitive function is biologically plausible, but this study suggests no such association in a community-based sample of the elderly.
Abstract: Homocysteine has been associated with an increased risk of cardiovascular disease. Cardiovascular diseases have been related to cognitive decline. The authors investigated the association of homocysteine with concurrent cognitive impairment and subsequent cognitive decline in a random sample of 702 community-dwelling respondents aged 55 years or over to the prospective Rotterdam Study in 1990-1994. Multiple logistic regression was used to calculate odds ratios and 95 percent confidence intervals for the association between total homocysteine levels and cognitive impairment (Mini-Mental State Examination (MMSE) score 1 point/year). Mean duration of follow-up was 2.7 years. After adjustment for age, sex, and education, there was no relation between total homocysteine and cognitive impairment (highest vs. lowest tertile: odds ratio (OR) = 1.30, 95% confidence interval (CI): 0.50, 3.38) or cognitive decline (middle vs. lowest tertile: OR = 1.14, 95% CI: 0.67, 1.93; highest vs. lowest tertile: OR = 0.91, 95% CI: 0.52, 1.58). Subjects who were lost to follow-up due to death or nonresponse had slightly higher age-adjusted homocysteine levels and lower MMSE scores at baseline. Sensitivity analyses showed that selective loss to follow-up was not a likely explanation for the absence of an association in the participants. Although a relation between homocysteine and reduced cognitive function is biologically plausible, this study suggests no such association in a community-based sample of the elderly.

Journal ArticleDOI
TL;DR: Bulbar-onset ALS patients with cognitive impairments and neuronal loss in the anterior cingulate gyrus subsequently developed more profound neuropsychological dysfunction whereas both language and speech capabilities remained relatively preserved.
Abstract: Objective: To characterize prospectively the cognitive profile in ALS. Methods: Clinically definite ALS patients (11 men, 2 women), age 39.9 to 74.0 years (mean age, 54.2 ± 9.6 years; mean disease duration, 21.1 ± 10.5 months) underwent neuropsychologic, language, and speech testing followed by MR 1H spectroscopy (4 T). Five spousal control subjects completed an identical protocol. Eight ALS patients participated in follow-up studies at a 6-month interval. Results: Relative to control subjects, ALS patients showed mild impairment in word generation, recognition memory (faces), and motor-free visual perception. Bulbar-onset patients showed greater impairment in a number of measures (working memory, problem solving/cognitive flexibility, visual perception, and recognition memory for words and faces), and cognitive impairment appeared more progressive over time. ALS patients demonstrated anomia on a confrontation naming test, with no significant problems following commands or repeating. Speech motor performance scores and intelligibility scores were not significantly different. No significant declines in forced vital capacity, forced expiratory volume, or peak expiratory flow rates were observed. Although normal at initial testing (T1), MR 1H spectroscopy demonstrated a reduction of the N-acetylaspartate/creatine (NAA/Cr) ratio in the nondominant precentral motor strip across the two testing intervals. In contrast, the NAA/Cr ratio obtained from the anterior cingulate gyrus at T1 was already reduced in bulbar-onset patients (p Conclusions: Bulbar-onset ALS patients with cognitive impairments and neuronal loss in the anterior cingulate gyrus subsequently developed more profound neuropsychological dysfunction whereas both language and speech capabilities remained relatively preserved. Of note, the absence of bulbar signs did not predict an absence of cognitive decline.

Journal ArticleDOI
TL;DR: Since CABG is increasingly done in older patients with more comorbidity, the challenge is to identify patients at risk of adverse neurocognitive outcomes and to protect them by modification of the surgical procedure or by effective medical therapy.

Journal ArticleDOI
TL;DR: A profile of individuals nonadherent to their medications in an age‐stratified sample (ages 34–84) of community‐dwelling rheumatoid arthritis patients is created.
Abstract: OBJECTIVES: To create a profile of individuals nonadherent to their medications in an age-stratified sample (ages 34–84) of community-dwelling rheumatoid arthritis patients. The relative contributions of age, cognitive function, disability, emotional state, lifestyle, and beliefs about illness to nonadherence were assessed. DESIGN: A direct observation approach was used in conjunction with structural equation modeling. All participants were administered a preliminary assessment battery. Medications were then transferred to vials with microelectronic caps that recorded medication events for all medications for the next 4 weeks. PARTICIPANTS AND SETTING: A volunteer sample of 121 community-dwelling rheumatoid arthritis (RA) patients were recruited from newspaper ads, posters, and via informal physician contact from private rheumatology practices in Atlanta and Athens, Georgia. Written verification of the RA diagnosis and a disease severity rating were obtained from personal physicians before patients were enrolled in the study. Patients were tested in a private physician's office, and their medication adherence was monitored electronically for a month in their every-day work and home settings. MEASUREMENTS AND RESULTS: Structural equation modeling techniques were used to develop a model of adherence behavior. Cognitive and psychosocial measures were used to construct latent variables to predict adherence errors. The model of medication adherence explained 39% of the variance in adherence errors. The model demonstrated that older adults made the fewest adherence errors, and middle-aged adults made the most. A busy lifestyle, age, and cognitive deficits predicted nonadherence, whereas coping with arthritis-related moods predicted adherence. Illness severity, medication load, and physical function did not predict adherence errors. Omission of medication accounted for nearly all errors. CONCLUSION: Despite strong evidence for normal, age-related cognitive decline in this sample, older adults had sufficient cognitive function to manage medications. A busy lifestyle and middle age were more determinant of who was at risk of nonadherence than beliefs about medication or illness. Thus, practicing physicians should not assume that older adults have insufficient cognitive resources to manage medications and that they will be the most likely to make adherence errors. Very busy middle-aged adults seem to be at the greatest risk of managing medications improperly. J Am Geriatr Soc 47:172–183, 1999.

Journal ArticleDOI
TL;DR: Comparisons between nondemented literate and illiterate elders in an epidemiological study of normal aging and dementia in the Northern Manhattan community revealed a significant overall effect for literacy status on neuropsychological test performance when groups were matched on years of education.
Abstract: The current investigation compared neuropsychological test performance among nondemented literate and illiterate elders. The sample included participants in an epidemiological study of normal aging and dementia in the Northern Manhattan community. All participants were diagnosed as nondemented by a neurologist, and did not have history of Parkinson's disease, stroke, or head injury. Literacy level was determined by self-report. MANOVAs revealed a significant overall effect for literacy status (literate vs. illiterate) on neuropsychological test performance when groups were matched on years of education. The overall effect of literacy status remained significant after restricting the analyses to elders with no formal education, and after controlling for the effects of language of test administration. Specifically, illiterates obtained lower scores on measures of naming, comprehension, verbal abstraction, orientation, and figure matching and recognition. However, tests of verbal list delayed recall, nonverbal abstraction, and category fluency were unaffected by literacy status, suggesting that these measures can be used to accurately detect cognitive decline among illiterate elders in this sample. Differences in organization of visuospatial information, lack of previous exposure to stimuli, and difficulties with interpretation of the logical functions of language are possible factors that contribute to our findings. (JINS, 1999, 5, 191–202.)

Journal ArticleDOI
TL;DR: It is suggested that subcortical brain regions exhibit greater vulnerability to the effects of aging than cortical regions, and neurotrophin gene transfer may be an effective means of preventing neuronal atrophy or degeneration in age-related neurodegenerative disorders.
Abstract: The effects of normal aging on the primate brain are incompletely understood. Although both human and nonhuman primates demonstrate clear functional declines in selective attention, “executive” functions, and some components of declarative memory with aging, most studies have failed to demonstrate extensive neuronal atrophy or loss as a substrate for these degenerative changes in primates. In particular, extensive age-related neuronal loss in memory-related brain regions such as the hippocampus and entorhinal cortex has not been found. However, it is possible that neuronal loss or atrophy might occur in subcortical nuclei that modulate the activity of neocortical regions, thereby accounting for altered cognitive function with aging. In the present study, we describe, to our knowledge for the first time, a significant and extensive decline in the number and size of immunolabeled neurons in subcortical cholinergic basal forebrain regions of aged rhesus monkeys, the best animal model of human aging, by using stereological methods. Notably, the loss of subcortical cholinergic neuronal markers in aged monkeys was nearly completely reversed by human nerve growth factor gene delivery. These findings (i) identify reversible cellular atrophy as a potential mechanism contributing to age-related cognitive decline in primates, (ii) suggest, when considered with other studies, that subcortical brain regions exhibit greater vulnerability to the effects of aging than cortical regions, and (iii) indicate that neurotrophin gene transfer may be an effective means of preventing neuronal atrophy or degeneration in age-related neurodegenerative disorders.

Journal ArticleDOI
TL;DR: Large between-centre differences in depression symptoms were not explained by demography or by the depression measure used in the survey, suggesting depression may be overdiagnosed in older persons because of an increase in lack of motivation.
Abstract: BACKGROUND Data from surveys involving 21,724 subjects aged > or = 65 years were analysed using a harmonised depression symptom scale, the EURO-D. AIMS To describe and compare the effects of age, gender and mental status on depressive symptoms across Europe. METHOD We tested for the effects of centre, age, gender and marital status on EURO-D score. Between-centre variance was partitioned according to centre characteristics: region, religion and survey instrument used. RESULTS EURO-D scores tended to increase with age, women scored higher than men, and widowed and separated subjects scored higher than others. The EURO-D scale could be reduced into two factors: affective suffering, responsible for the gender difference, and motivation, accounting for the positive association with age. CONCLUSIONS Large between-centre differences in depression symptoms were not explained by demography or by the depression measure used in the survey. Consistent, small effects of age, gender and marital status were observed across Europe. Depression may be overdiagnosed in older persons because of an increase in lack of motivation that may be affectively neutral, and is possibly related to cognitive decline.

Journal ArticleDOI
TL;DR: Cognitive and functional decline can be detected in a short-term follow-up in a subset of geriatric long-stay patients with schizophrenia, and appears distributed across patients and not due to the presence of progressive degenerative dementing conditions.

Journal ArticleDOI
TL;DR: It is suggested that TBI causes loss of K+ conductance in hippocampal glia that results in the failure of glial K+ homeostasis, which in turn promotes abnormal neuronal function.
Abstract: Traumatic brain injury (TBI) can be associated with memory impairment, cognitive deficits, or seizures, all of which can reflect altered hippocampal function. Whereas previous studies have focused on the involvement of neuronal loss in post-traumatic hippocampus, there has been relatively little understanding of changes in ionic homeostasis, failure of which can result in neuronal hyperexcitability and abnormal synchronization. Because glia play a crucial role in the homeostasis of the brain microenvironment, we investigated the effects of TBI on rat hippocampal glia. Using a fluid percussion injury (FPI) model and patch-clamp recordings from hippocampal slices, we have found impaired glial physiology 2 d after FPI. Electrophysiologically, we observed reduction in transient outward and inward K(+) currents. To assess the functional consequences of these glial changes, field potentials and extracellular K(+) activity were recorded in area CA3 during antidromic stimulation. An abnormal extracellular K(+) accumulation was observed in the post-traumatic hippocampal slices, accompanied by the appearance of CA3 afterdischarges. After pharmacological blockade of excitatory synapses and of K(+) inward currents, uninjured slices showed the same altered K(+) accumulation in the absence of abnormal neuronal activity. We suggest that TBI causes loss of K(+) conductance in hippocampal glia that results in the failure of glial K(+) homeostasis, which in turn promotes abnormal neuronal function. These findings provide a new potential mechanistic link between traumatic brain injury and subsequent development of disorders such as memory loss, cognitive decline, seizures, and epilepsy.

Journal ArticleDOI
TL;DR: A difference in processing speed's ability to account for cross-section and longitudinal age effects is discussed in the context of theories of cognitive aging and methodological and statistical issues pertaining to the cross-sectional and longitudinal study of Cognitive aging.
Abstract: Cross-sectional and longitudinal age effects on cognitive function were examined in 302 older adults followed longitudinally. Processing speed was related to cognitive performance at cross-section, and change in speed predicted within-person longitudinal cognitive decline. Statistical control of processing speed greatly reduced cross-sectional age effects but did not attenuate longitudinal aging effects. This difference in processing speed's ability to account for cross-sectional and longitudinal age effects is discussed in the context of theories of cognitive aging and methodological and statistical issues pertaining to the cross-sectional and longitudinal study of cognitive aging.

Journal ArticleDOI
TL;DR: The use of diuretics may protect against dementia in elderly persons and was related to a reduced risk of Alzheimer disease only in the subpopulation with a higher baseline blood pressure.
Abstract: Objective To examine whether antihypertensive medication use can affect the occurrence and progression of dementia. Subjects and Methods In a community cohort of 1810 persons aged 75 years and older, 225 prevalent cases of dementia were detected. Among the 1301 persons without dementia, 224 incident cases of dementia were identified during an average period of 3 years. Among the 225 prevalent cases of dementia, 79 were suitable for the analysis of cognitive decline. Information on drug use was collected for the 2 weeks preceding the baseline interview. Results Subjects taking antihypertensive medication (n=651, 83.9% of whom took diuretics) had a lower prevalence of dementia than those not taking antihypertensive medication ( P P =.03). Furthermore, subjects taking diuretics (n=484) had an adjusted relative risk of 0.7 (95% confidence interval, 0.5-1.0; P =.02) for all dementia, and subjects taking diuretic monotherapy (n=345) had an adjusted relative risk of 0.6 (95% confidence interval, 0.4-0.9; P =.006). The use of other antihypertensive medication (calcium antagonists or β-blockers), however, was related to a reduced risk of Alzheimer disease (adjusted relative risk, 0.6; 95% confidence interval, 0.3-1.2) only in the subpopulation with a higher baseline blood pressure (n=458). Patients with dementia at baseline who were not taking diuretics had a 2-fold faster rate of decline in the score on the Mini-Mental State Examination than those taking diuretics. Conclusion The use of diuretics may protect against dementia in elderly persons.

Journal ArticleDOI
TL;DR: The authors’ findings demonstrate a relation between education and age-related cortical atrophy in a nonclinical sample of elderly persons, and are consistent with the reserve hypothesis as well as with a small number of brain imaging studies in patients with dementia.
Abstract: Objective: To examine the relations between education and age-related changes in brain structure in a nonclinical sample of elderly adults. Background: Education may protect against cognitive decline in late life—an observation that has led to the “reserve” hypothesis of brain aging. Little is known, however, about the effect of education on age-related changes in brain structure. Methods: Quantitative MRI of the brain was performed in 320 elderly volunteers (age range, 66 to 90 years) living independently in the community (Mini-Mental State Examination scores ≥ 24), all of whom were participants in the Cardiovascular Health Study. Blinded measurements of global and regional brain size were made from T1-weighted axial images using computer-assisted edge detection and trace methodology. High measurement reliabilities were obtained. Results: Regression analyses (adjusting for the effects of intracranial size, sex, age, age-by-sex interactions, and potential confounders) revealed significant main effects of education on peripheral (sulcal) CSF volume—a marker of cortical atrophy. Each year of education was associated with an increase in peripheral CSF volume of 1.77 mL ( p Conclusions: The authors’ findings demonstrate a relation between education and age-related cortical atrophy in a nonclinical sample of elderly persons, and are consistent with the reserve hypothesis as well as with a small number of brain imaging studies in patients with dementia. The neurobiological basis and functional correlates of this education effect require additional investigation.

Journal ArticleDOI
01 May 1999-Brain
TL;DR: Results indicate that, despite some cognitive overlap between the two tasks and the age-related cognitive decline in both, many of the changes in rCBF activation with age were task-specific, reflecting functional alteration of the different neural circuits normally engaged by young subjects during the WCST and RPM.
Abstract: We used PET to explore the neurophysiological changes that accompany cognitive disability in ageing, with a focus on the frontal lobe. Absolute regional cerebral blood flow (rCBF) was measured in 41 healthy volunteers, evenly distributed across an age range of 18-80 years, during two task paradigms: (i) the Wisconsin Card Sorting Test (WCST), which depends heavily on working memory and is particularly sensitive to dysfunction of the dorsolateral prefrontal cortex (DLPFC); and (ii) Raven's Progressive Matrices (RPM), which may also have a working memory component, but depends more on visuo-spatial processing and is most sensitive to dysfunction of postrolandic regions. We used voxel-wise correlational mapping to determine age-related changes in WCST and RPM activation and developed a method to quantitate and localize statistical differences between the correlation maps for the two task paradigms. Because both WCST and RPM performance declined with age, as expected, correlational analyses were performed with and without partialling out the effect of task performance. Task-specific reductions of rCBF activation with age were found in the DLPFC during the WCST and in portions of the inferolateral temporal cortex involved in visuo-spatial processing during the RPM. We also found reduced ability to suppress rCBF in the right hippocampal region during the WCST and in mesial and polar portions of the prefrontal cortex during both task conditions. Task-dependent alterations with age in the relationship between the DLPFC and the hippocampus were also documented; because the collective pattern of changes in the hippocampal-DLPFC relationship with ageing was opposite to that seen in a previous study using dextroamphetamine, we postulated a dopaminergic mechanism. These results indicate that, despite some cognitive overlap between the two tasks and the age-related cognitive decline in both, many of the changes in rCBF activation with age were task-specific, reflecting functional alteration of the different neural circuits normally engaged by young subjects during the WCST and RPM. Reduced activation of areas critical for task performance (i.e. the DLPFC during the WCST and posterior visual association areas of the inferolateral temporal cortex during the RPM), in conjunction with the inability to suppress areas normally not involved in task performance (i.e. the left hippocampal region during the WCST and mesial polar prefrontal cortex during both the WCST and RPM), suggest that, overall, reduced ability to focus neural activity may be impaired in older subjects. The context dependency of the age-related changes is most consistent with systems failure and disordered connectivity.

Journal ArticleDOI
TL;DR: This study establishes age-related memory decline using longitudinal data, and shows that this decline does not occur diffusely across multiple cognitive domains, and anatomically localizes to the hippocampus.
Abstract: Objective: To use longitudinally acquired data to establish whether aging is associated with memory decline. Background: Memory loss is one of the most frequent complaints among the elderly. Nevertheless, age-related memory decline remains controversial in large part because it has been established with cross-sectional studies. Methods: A total of 212 community-based healthy people were followed prospectively and evaluated annually with a neuropsychological battery testing memory and other cognitive domains. To control for the learning effect—the improvement in test performance associated with repeated exposure—longitudinal performance was compared between two age groups. Results: The older age group displayed a relative decline in memory performance with time. In contrast to memory, a relative age-related decline was not observed in tests of language, visuospatial ability, and abstract reasoning. Furthermore, within the memory domain, age-related decline was restricted to a specific aspect of memory, manifesting only in a measure sensitive to the acquisition and early retrieval of new information, and not in a measure of memory retention. This profile of age-related cognitive decline anatomically localizes to the hippocampal formation. Conclusion: This study establishes age-related memory decline using longitudinal data, and shows that this decline does not occur diffusely across multiple cognitive domains. Both early AD as well as non-AD processes likely contribute to age-related memory decline, and continued follow-up may reveal distinguishing features between these two.

Journal ArticleDOI
TL;DR: The purpose of this study was to evaluate the cross‐sectional and longitudinal association of oral estrogen replacement therapy (ERT) and cognitive function in an older, nondemented sample of women.
Abstract: BACKGROUND: The purpose of this study was to evaluate the cross-sectional and longitudinal association of oral estrogen replacement therapy (ERT) and cognitive function in an older, nondemented sample of women. METHODS: In a prospective cohort of 9651 white women aged 65 years and older enrolled in the Study of Osteoporotic Fractures, a modified Mini-Mental Status Exam (mMMSE), and digit symbol substitution and Trails B tests were administered twice, 4 to 6 years apart. History and current use of oral ERT was documented. Age, educational attainment, and activity limitations were the primary covariates in the analyses; in addition, stroke and depression scores were adjusted in subsets of women with available data. RESULTS: Current and past users of ERT had better initial scores on the mMMSE than did never users, P < .05 and .001, respectively, with better scores for current estrogen hormone users being most apparent among the older and less educated women. The percentages of women scoring ≤23 of a possible 26 on the mMMSE were 14.3 for current users, 14.5 for past users, and 20.5 for never users, P < .001. However, only past users exhibited smaller declines upon retesting in mMMSE and Trails B performance, P < .05, than did never users. Educational attainment predicted both initial test scores and change scores and was, next to age, the most powerful predictor of cognitive function. CONCLUSIONS: Current oral ERT does not protect against age-related declines in cognitive function in older nondemented women, whereas formal education does protect, even though it had been completed many years earlier. The influence of education in late-life on cognitive function should be tested. J Am Geriatr Soc 47:518–523, 1999.

Journal ArticleDOI
TL;DR: Anger, sadness, and disgust were less recognized in FTD than in AD patients who did not differ from controls, whereas fear and contempt were poorly recognized in both groups of patients compared with controls, arguing for different neural substrates underlying the recognition of various basic emotions.
Abstract: Frontotemporal dementia (FTD) is the second cause of degenerative dementia. Behavioral changes occur before the cognitive decline and remain the major feature. A poor perception of emotion could account for some behavioral symptoms. The aim of this study was to assess the perception of emotion in patients with FTD and to compare it with that of patients with Alzheimer disease (AD). Fifty subjects performed the tests: 20 patients with probable AD, 18 patients with FTD, and 12 matched controls. The two patient groups did not differ in age, sex, severity of dementia, duration of the disease, and language tests. Subjects had to recognize and point out the name of one of seven basic emotions (anger, disgust, happiness, fear, sadness, surprise, and contempt) on a set of 28 faces presented on slides. The three groups were equally able to distinguish a face displaying affect from one not displaying affect. Naming of emotion was worse in patients with FTD than in patients with AD (correct answers 46% vs. 62%; p = 0.0006) who did not differ significantly from controls (72%). Anger, sadness, and disgust were less recognized in FTD than in AD patients who did not differ from controls, whereas fear and contempt were poorly recognized in both groups of patients compared with controls. These findings argue for different neural substrates underlying the recognition of various basic emotions. Behavioral disorders in FTD may be partly due to an impaired interpretation of the emotional environment.