Showing papers on "Cognitive decline published in 1996"
TL;DR: The findings demonstrate that hippocampal neuronal degeneration is not an inevitable consequence of normal aging and that a loss of principal neurons in the hippocampus fails to account for age-related learning and memory impairment.
Abstract: Hippocampal neuron loss is widely viewed as a hallmark of normal aging. Moreover, neuronal degeneration is thought to contribute directly to age-related deficits in learning and memory supported by the hippocampus. By taking advantage of improved methods for quantifying neuron number, the present study reports evidence challenging these long-standing concepts. The status of hippocampal-dependent spatial learning was evaluated in young and aged Long-Evans rats using the Morris water maze, and the total number of neurons in the principal cell layers of the dentate gyrus and hippocampus was quantified according to the optical fractionator technique. For each of the hippocampal fields, neuron number was preserved in the aged subjects as a group and in aged individuals with documented learning and memory deficits indicative of hippocampal dysfunction. The findings demonstrate that hippocampal neuronal degeneration is not an inevitable consequence of normal aging and that a loss of principal neurons in the hippocampus fails to account for age-related learning and memory impairment. The observed preservation of neuron number represents an essential foundation for identifying the neurobiological effects of hippocampal aging that account for cognitive decline.
665 citations
TL;DR: It is concluded that subjective memory complaints may predict dementia within 3 years, particularly when there are objective signs of memory deterioration.
Abstract: Whether subjective memory complaints in the absence of objective memory decline can predict future dementia has been investigated only in highly selected clinical and volunteer cohorts. Our study examines this question in a subsample of AMSTEL (Amsterdam Study of the Elderly), a longitudinal population study on cognitive decline and dementia. Subjects (aged 65 to 84 years; n = 357) without dementia or other psychiatric disorders at baseline were followed for 3 years. After this interval, 16 of 203 re-examined patients developed a dementia. Logistic regression analyses indicated that memory complaints at baseline contributed a small but significant amount of diagnostic information. However, the most powerful predictor of future dementia was deficient memory performance. We conclude that subjective memory complaints may predict dementia within 3 years, particularly when there are objective signs of memory deterioration.
325 citations
TL;DR: It is suggested that the cognitive declines evident in the rhesus monkey may be a consequence of changes in layer I and in the integrity of myelinated axons, rather than an agerelated loss of cortical neurons or synapses, as has long been assumed.
Abstract: The rhesus monkey offers a useful model of normal human aging because when monkeys are tested on a battery of behavioral tasks that can also be used to evaluate cognition in humans, it is found that the monkeys undergo an age-related decline in several domains of cognitive function as do humans. In monkeys these changes begin at about 20 years of age. To determine what gives rise to this cognitive decline, we have examined several parameters in the brains of monkeys. Some parameters do not change with age. Examples of this are the numbers of neurons in the neocortex and hippocampal formation, and the numbers of synapses in the hippocampal formation. Changes in other parameters can be positively correlated with chronological age; examples of this are numbers of neuritic plaques, a decrease in the numbers of neurons in the striatally projecting pars compacta of the substantia nigra, and a decrease in the thickness of layer I in primary visual cortex. But the most interesting changes are those that correlate either with cognitive decline alone, or with both cognitive decline and chronological age. Among these are a breakdown in the integrity of myelin around axons, an overall reduction in the volume of white matter in the cerebral hemispheres, thinning of layer I in area 46 of prefrontal cortex, and decreases in the cell density in cortically projecting brain stem nuclei. To date then, our studies suggest that the cognitive declines evident in the rhesus monkey may be a consequence of changes in layer I and in the integrity of myelinated axons, rather than an age-related loss of cortical neurons or synapses, as has long been assumed.
293 citations
TL;DR: The findings suggest that the beneficial effects of dietary restriction upon brain function and life span may depend upon its ability to acutely reduce steady-state levels of oxidative stress.
286 citations
TL;DR: In this article, the Modified Mini-Mental State Examination (3MS) has been extended with four additional subtests (date and place of birth, word fluency, similarities, and delayed recall of words).
Abstract: study, 525 community-dwelling participants, aged 65-89, were divided into 2 groups: no cognitive impairment (NCI; n - 406) and Alzheimer's disease (n = 119). Both tests yielded comparable reliability estimates. Fewer years of education decreased specificity and increased sensitivity, whereas increasing age primarily decreased specificity. It is concluded that although the 2 tests produce comparable effects, the inclusion of a verbal fluency test would increase the sensitivity of the MMSE. Normative data for the NCI group, stratified for 2 age levels (65-79 and 80-89) and 2 educational levels (0-8 and 9+ years), are presented. Folstein, Folstein, and McHugh (1975) introduced the MiniMental State Examination (MMSE) as a brief, objective assessment of cognitive functioning and as a measure of changes in cognitive status. The MMSE usually can be administered in 510 min and has been employed extensively in clinical settings, community surveys, and epidemiological studies. In a recent review of the literature, Tombaugh and Mclntyre (1992) concluded that the MMSE possessed moderate to high reliability coefficients, demonstrated high levels of sensitivity for cognitive deficits in patients suffering from moderate to severe Alzheimer's disease, and reflected the cognitive decline typical of dementia patients. Criticisms of the MMSE included (a) its failure to discriminate between people with mild dementia and those who are not demented, (b) a limited ability to detect impairment caused by focal lesions, particularly those in the right hemisphere, (c) overly simple language items that reduce sensitivity to mild linguistic deficits, and (d) a large number of false-positive errors because of its bias against individuals with low education. In response to these problems, several attempts have been made to improve the MMSE. Of these, the Modified Mini-Mental State Examination (3MS; Teng & Chui, 1987) represents the most extensive revision. Teng and Chui (1987) added four additional subtests (date and place of birth, word fluency, similarities, and delayed recall of words). The maximum score was
277 citations
TL;DR: In this paper, a large variation in reported incidence of cognitive decline after coronary artery bypass grafting can be attributed to the different criteria used to define cognitive impairment, and there was little agreement between the criteria as to which patients decline at each test period.
270 citations
TL;DR: In this article, the authors used the aged canines as a model for studying early degeneration normally considered to be pre-Alzheimer's and found that the extent of beta-amyloid deposition correlates with a decline in select measures of cognitive function.
254 citations
TL;DR: Results indicate that once psychiatric symptoms are present in patients with Alzheimer's disease, they frequently recur, and these symptoms vary with age, sex, and rate of illness progression.
Abstract: Objective: The goal of this study was to define the recurrence or continuation of neuropsychiatric symptoms iii patients u’ith Alzheimer’s disease who were observed serially for a 1-year period. Method: One hundred eighty-one patients tvith probable Alzheimer ‘s disease were assessed five times at 3-monti, intervals with a standardized neuropsychiatric rating instrumemit. Results: Recurrence rates of neuropsychiatric symptoms during the 1-year period u’ere 85% for depression, 93% for agitation, and 95% for psychosis. Symptom frequency at any point in time underestimated the cumulative 1 -year frequency. Recurrence rates were sigmzificant!) greater among patients tt’ho had multiple symptoms. Women exhibited more symptoms thami mcmi. Patients in the oldest age group (76-87 years) had more psychosis, less depression and agitation, and slower cognitive declimie. Psychosis was associated with muzore rapid cognitive decline, amid agitation was associated with more rapid functional deterioration. Conclusions: These results indicate that omucepsychiatric symptoms are present in patiemits with Alzheimner’s disease, they frequently recur. These symptoms vary with age, sex, amid rate of ill,zess progression. (AmJ Psychiatry 1996; 153:1438-1443)
242 citations
TL;DR: The association of apathetic syndromes with prefrontal and anterior temporal regional brain dysfunction is demonstrated and is consistent with similar findings previously reported in other disorders.
Abstract: Design: Analysis of the relationship between regional cerebral blood flow as measured by single photon emission computed tomography and severity of apathy as measured by the Neuropsychiatric Inventory using an analysis of variance design. We examined regional cerebral perfusion alterations as measured by xenon 133Xecalibrated technetium Tc 99m hexamethyl-propy\x=req-\ leneamine-oxime single photon emission computed tomography in relation to the presence and severity of apathy. and Harbor-UCLA Medical Center. Participants: Thirty-one community-dwelling patients fulfilling National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association diagnostic criteria for probable Alzheimer disease who had a single photon computed tomographic scan performed within 3 months of administration of the Neuropsychiatric Inventory. Results: The presence of apathy was associated with more severe prefrontal and anterior temporal dysfunction. These regional cerebral perfusion relationships with apathy were independent of cognitive decline except in the dorsolateral prefrontal cortex. Conclusions: These results demonstrate the association of apathetic syndromes with prefrontal and anterior temporal regional brain dysfunction and are consistent with similar findings previously reported in other disorders. ArchNeurol. 1996;53:1116-1120
221 citations
TL;DR: Results reported here, combined with previous clinical and experimental reports, indicate that the risk of memory impairment should be carefully considered before initiating treatment with glucocorticoids and that the potential benefit of anti-inflammatory treatment in Alzheimer's disease might be counterbalanced by possible iatrogenic memory impairment.
Abstract: There have been no systematic investigations of the effects of glucocorticoid treatment on memory in a clinical population despite experimental and clinical evidence that such treatment could cause memory disturbance.We conducted both cross-sectional and longitudinal studies. In Study 1, we administered tests of both hippocampal-dependent explicit memory and hippocampal-independent implicit memory to twenty-five prednisone-treated patients with systemic disease without CNS involvement and 25 matched clinical controls. All treated patients were taking doses of 5 to 40 mg of prednisone daily for at least 1 year. The glucocorticoid-treated group performed worse than the controls on tests of explicit memory, but the groups did not differ on the implicit memory task. Multiple regression analyses suggested that elderly patients are more susceptible to memory impairment with less protracted treatment. The results of Study 2, a prospective, longitudinal study of the effects of prednisone on memory across 3 months of therapy, suggest that even acute treatment can adversely affect memory. The observed alteration in memory was not secondary to inattention, affective disturbance, generalized global cognitive decline, or severity of disease. Results reported here, combined with previous clinical and experimental reports, indicate that the risk of memory impairment should be carefully considered before initiating treatment with glucocorticoids. Conversely, use of glucocorticoids should be considered in the differential diagnosis of memory loss. Finally, the potential benefit of anti-inflammatory treatment in Alzheimer9s disease might be counterbalanced by possible iatrogenic memory impairment, at least when synthetic glucocorticoids are considered. NEUROLOGY 1996;47: 1396-1402
206 citations
TL;DR: It is suggested that apoE genotyping will have limited utility as a diagnostic or prognostic indicator of cognitive decline in individuals, as many individuals reach old age without cognitive impairment despite inheritance of one or two APoE ε4 alleles.
Abstract: The apolipoprotein E (apoE) epsilon 4 allele is overrepresented, and the apoE epsilon 2 allele underrepresented, in Alzheimer's disease. To assess the risk of cognitive impairment in individuals with these genotypes in the general population, we studied a population-based sample of 1,899 individuals 65 years and older as a follow-up to the Iowa 65+ Rural Health Study. Multiple regression and logistic regression analyses demonstrated significant effects of apoE epsilon 4 and apoE epsilon 2 in predicting performance on a delayed recall task over a 4- to 7-year period. The magnitude of this effect was, however, fairly modest, with odds ratios for developing impairment of approximately 1.37 (95% confidence interval: 1.007, 1.850; p = 0.045) for apoE epsilon 4 and 0.53 (95% confidence interval: 0.368, 0.777; p = 0.001) for apoE epsilon 2. These effects were more pronounced in women than men. Importantly, 85% of elderly apoE E4/4 individuals (average age, 81) scored in the unimpaired range on a screening mental status test. Thus, many individuals reach old age without cognitive impair- ment despite inheritance of one or two apoE epsilon 4 alleles. This suggests that apoE genotyping will have limited utility as a diagnostic or prognostic indicator of cognitive decline in individuals.
TL;DR: Moclobemide was shown to be a safe, well tolerated and effective antidepressant, which did not cause impairment of cognitive function in elderly patients with a DSM–III diagnosis of dementia and/or DSM-III major depression.
Abstract: BACKGROUND The new reversible MAOl moclobemide was compared with placebo in the treatment of elderly patients with DSM-III diagnosis of dementia and/or of major depression.
METHOD Six hundred and ninety-four elderly patients with symptoms of depression and cognitive decline entered an international, multi-centre, double blind trial in which they were randomly allocated to treatment with either moclobemide 400 mg daily or placebo for 42 days. Five hundred and eleven patients met DSM-III criteria for dementia and were also depressed (DEM+D); 183 did not meet DSM-III criteria for dementia but met the criteria for DSM-III major depressive episode and also suffered from cognitive decline (MDE+CD).
RESULTS Analysis of the 17 and 24-item Hamilton Depression Scale scores showed that moclobemide, compared with placebo, produced significantly greater improvement in both the demented and depressed groups (P = 0.001 both diagnostic groups). There was an improvement in cognitive function as measured by the SCAG Factor 1 in moclobemide treated patients (P = 0.005 DEM+D; P = 0.02 MDE+CD). There was no evidence of decline in cognitive function as the result of treatment. Clinical global assessment of tolerance was 'excellent' and 'good' in 88% of the moclobemide and in 92% of the placebo treated patients. The proportion of patients discontinuing treatment prematurely was similar in both treatment groups. There were no significant differences in side-effects between treatment groups. There were no significant changes in vital signs, ECG or laboratory findings in either treatment group. There were no dietary restrictions and no report of any tyramine reaction.
CONCLUSIONS Moclobemide was shown to be a safe, well tolerated and effective antidepressant, which did not cause impairment of cognitive function in elderly patients with a DSM-III diagnosis of dementia and/or DSM-III major depression.
TL;DR: The findings do not support the hypothesis of a protective effect of smoking on cognitive function; they suggest that smoking may be harmful among those with CVD/diabetes.
Abstract: The authors examine the cross-sectional and longitudinal relation of smoking habits and current alcohol intake to cognitive status and decline over a 3-year period as well as the extent to which these relations are modified by the presence of clinical conditions indicating atherosclerosis (cardiovascular disease (CVD)/diabetes). Data are from the cohort of men followed in the longitudinal Zutphen Elderly Study in 1990 (n = 489) and 1993 (n = 333). Cognitive function was measured in 1990 and 1993 with the 30-point Mini-Mental State Examination (MMSE). After adjustment for age, education, and alcohol intake, current smokers made 20% more errors on the MMSE than never smokers in the cross-sectional analyses. Cognitive decline was greatest in those with CVD/diabetes who currently smoked and never smoked (-1.9 and -1.3 points, respectively). After adjustment for age, education, and smoking status, men with CVD/diabetes and low-to-moderate alcohol intake had a significantly lower risk for poor cognitive function (MMSE < or = 25) than abstainers (odds ratios of 0.3 for less than one drink and 0.2 for one to two drinks per day). Alcohol intake was not associated with cognitive decline. These findings do not support the hypothesis of a protective effect of smoking on cognitive function; they suggest that smoking may be harmful among those with CVD/diabetes. Alcohol may result in an acute beneficial effect on cognitive function among those with CVD/diabetes. However, selection bias and unmeasured confounding should be of concern when evaluating these results.
TL;DR: Central auditory dysfunction precedes senile dementia in a significant number of cases and may be an early marker for senile Alzheimer's disease.
Abstract: Objectives: To determine in older people the relation between auditory dysfunction and cognitive dysfunction, and if central auditory test abnormalities predict the onset of clinical dementia or cognitive decline. Design: Prospective population-based cohort study. Setting: Framingham Heart Study outpatient biennial examinations 18 and 21. Participants: Members of the Framingham Heart Study cohort with normal findings from cognitive screening tests at biennial examination 18. Measurements: Peripheral audiometric thresholds and word recognition in quiet; Synthetic Sentence Identification with Ipsilateral Competing Message (SSI-ICM); Mini-Mental State Examination; and detailed neuropsychological testing of subjects with abnormal findings from the Mini-Mental State Examination. Relative risk of dementia was determined using age-adjusted Cox proportional hazards regression models. Results: Hearing loss significantly lowered performance on the verbal parts of the Mini-Mental State Examination. The relative risk of subsequent clinical dementia or cognitive decline was 6 in subjects with very poor scores ( Conclusions: Central auditory dysfunction precedes senile dementia in a significant number of cases and may be an early marker for senile dementia. Hearing tests should be included in the evaluation of persons older than 60 years and in those suspected of having cognitive dysfunction. (Arch Otolaryngol Head Neck Surg. 1996;122:161-167)
TL;DR: Cerebrovascular disease and APOE*4 may have a synergistic effect on cognitive decline and cardiovascular risk factors showed that the risk of cognitive decline was highest in subjects with both APoe*4 and a high cholesterol level, high fibrinogen level, normal blood pressure, or diabetes mellitus.
Abstract: Background and Purpose Cerebrovascular disease and the apolipoprotein e4 (APOE*4) allele are both important risk factors for cognitive decline. We investigated the combined effect of APOE*4 and cerebrovascular disease on cognitive decline. Methods Data are from a cohort of 353 men, aged 69 to 89 years at baseline, living in Zutphen, Netherlands. The 30-point Mini-Mental State Examination (MMSE) was used to measure cognitive decline (drop of >2 points) from 1990 to 1993 (14% of the sample). Odds ratios (OR [95% confidence interval]) for cognitive decline were adjusted for age, education, and baseline MMSE score. Results Compared with those without APOE*4 and without a history of cerebrovascular disease, the adjusted OR was 4.7 (1.7 to 12.7) for subjects without APOE*4 but with cerebrovascular disease, 3.3 (1.6 to 6.8) for those with APOE*4 and no cerebrovascular disease, and 17.2 (2.7 to 110.0) for those with both risk factors. The risk for cerebrovascular disease and APOE*4 combined was more than expected...
TL;DR: The results indicate that the mechanism placing individuals with an epsilon 4 allele at risk for developing AD does not influence the rate of cognitive decline, and imply that the influence of apoE ePSilon 4 either precedes or occurs at an early point in the AD disease process.
Abstract: Background: Inheritance of the apolipoprotein E (apoE) epsilon 4 allele is a risk factor for developing Alzheimer9s disease (AD) and is associated with a lower age of dementia onset. The purpose of this study was to determine whether apoE genotypes differentially influence the course of cognitive decline in AD dementia. Methods: We administered nine cognitive tests that assessed explicit memory, attention, language, visuospatial function, frontal-lobe function, and logical reasoning abilities to 66 probable AD patients every 6 to 24 months over a span of up to 5.5 years. We identified apoE genotype by a PCR-based method; there were 16 patients with epsilon 3/3, 34 with epsilon 3/4, and 16 with epsilon 4/4. Using regression statistical methods, we computed the change in performance for each test for each patient over time. We then analyzed the mean change in each test in patients grouped according to apoE genotype. Results: For the AD patients as a group, performance on all cognitive tests declined significantly over time, but the rate of decline did not vary significantly across apoE genotypes on any cognitive test. Specifically, the rate of cognitive decline was not faster in patients with an epsilon 4 allele than in those with epsilon 3/3. Conclusions: These results indicate that the mechanism placing individuals with an epsilon 4 allele at risk for developing AD does not influence the rate of cognitive decline. These observations imply that the influence of apoE epsilon 4 either precedes or occurs at an early point in the AD disease process. NEUROLOGY 1996;47: 444-448
TL;DR: The elevated risk of subsequent strokes in older persons with cognitive impairment suggests that CVD may play a larger role in causing cognitive impairment then previously suspected.
Abstract: OBJECTIVE: Recent studies have suggested that vascular dementia in older persons is more common than previously hypothesized. A substantial proportion of dementia in old age may be an early manifestation of cerebrovascular disease (CVD), that eventually becomes clinically evident as an acute cerebrovascular accident. This study was aimed at assessing whether cognitive impairment and cognitive decline in older persons free of stroke are associated with higher risk of future stroke, independently of other risk factors.
DESIGN: Population-based prospective study.
PARTICIPANTS: A total of 5024 subjects from the Established Populations for Epidemiologic Studies of the Elderly, who were alive and had no history of previous stroke at the sixth follow-up visit. Subjects who had reported a stroke in a previous interview or with a diagnosis of cerebrovascular disease in a hospitalization record during the previous 3 years were excluded.
MEASUREMENTS: Cognitive function was assessed by the Short Portable Mental Status Questionnaire (SPMSQ). Occurrence of a stroke was prospectively assessed by examining hospital discharge diagnoses and death certificates.
RESULTS: During 19,533 person-years of follow-up, 259 strokes were recorded (13.3/1000 person-years). Stroke incidence was lowest in those with normal SPMSQ score (12.1/1000 person-years), intermediate in those with moderate impairment (16.3/1000 person-years), and highest in those with severe impairment (30.9/1000 person-years). Adjusting for age, education, smoking, history of hypertension, blood pressure, heart attack, diabetes, and disability, the relative risks of stroke for moderate and severe cognitive impairment were 1.2 (0.9–1.6) and 2.2 (1.2–3.8), respectively. The association between cognitive impairment and incident stroke was not mediated by hypertension or diabetes. Compared with subjects with stable or improved SPMSQ score in the previous 3 years, those who declined had higher risk of stroke.
CONCLUSIONS: The elevated risk of subsequent strokes in older persons with cognitive impairment suggests that CVD may play a larger role in causing cognitive impairment then previously suspected. It remains to be demonstrated whether reducing modifiable risk factors for CVD decreases the burden of cognitive impairment in older persons without stroke. J Am Geriatr Soc 44:237–241, 1996.
TL;DR: The results suggest that the prevalence of AACD is lower than that of AAMI, and as AAMI tends to identify a very heterogeneous subject group, the AACD diagnosis might prove superior to AAMI in differentiating a meaningful subgroup from an elderly population both for research purposes and in clinical settings.
Abstract: Summary Different diagnostic definitions have been proposed for use in the characterization of mild cognitive disorders associated with ageing. Previously, we reported a high (38.4%) prevalence of age-associated memory impairment (AAMI) using the National Institute of Mental Health criteria in an elderly population. Recently, a work group of the International Psychogeriatric Association proposed criteria for 'ageing-associated cognitive decline' (AACD). The objective of this study was to evaluate the prevalence of AACD in an elderly population. We examined 403 randomly selected subjects (68-78 years of age) with tests of memory, cognitive processing, attention, verbal and visuoconstructive functions and with a structured questionnaire for health status and subjective complaints of cognitive decline. In all, 26.6% of the subjects (24.4% of women, 30.1% of men) fulfilled the AACD criteria. The prevalence was slightly related to age and education. The rate was lowest in the oldest age group of 75-78 years (20.5%) and highest in the age group of 71-74 years (30.5%). Subjects with less than 4 years of education had the lowest (14.3%) and subjects with more than 6 years of education had the highest rate (29.4%) for AACD. However, the differences between these subgroups were not statistically significant. These results suggest that the prevalence of AACD is lower than that of AAMI. As AAMI tends to identify a very heterogeneous subject group, the AACD diagnosis, which takes into account age and education specific norms in its inclusion criteria, might prove superior to AAMI in differentiating a meaningful subgroup from an elderly population both for research purposes and in clinical settings.
TL;DR: A brief neuropsychological test battery may be useful for early detection of HIV+ individuals with a poorer prognosis who may benefit from more aggressive treatment to prevent HIV dementia.
Abstract: The objective of this study was to determine if sustained decline in psychomotor speed tests is associated with an increased risk of progression to dementia, acquired immunodeficiency syndrome (AIDS), or mortality in human immunodeficiency virus (HIV)-1-infected homosexual men in the Baltimore site of the Multicenter AIDS Cohort-Study (MACS). Clinical and neuropsychological data were obtained on 291 HIV+ homosexual men seen semi-annually over a nine year period (1986-1994). A proportional hazards model was used to assess the predictive value of sustained psychomotor slowing (defined as a 2.0 standard deviation (s.d.) decline in performance on either the Symbol Digit Modalities test or Trailmaking test at two consecutive evaluations). Time-dependent co-variates included in the model were sustained psychomotor slowing, number of attended visits, CD4+ lymphocyte count, hemoglobin and antiretroviral medication use. HIV+ participants with and without sustained psychomotor slowing were compared. Outcome variables were the development of dementia, AIDS and death. HIV+ subjects with sustained psychomotor slowing had an increased hazard of dementia (Risk ratio (RR) = 5.0, P = 0.008), AIDS (RR = 2.4, P = 0.02), and death (RR = 2.0, P = 0.04). A similar analysis using sustained cognitive decline in one domain from a more extensive neuropsychological test battery failed to show any predictive value. Sustained decline in psychomotor performance in HIV infection was predictive of dementia, AIDS and death. This brief neuropsychological test battery may be useful for early detection of HIV+ individuals with a poorer prognosis who may benefit from more aggressive treatment to prevent HIV dementia.
TL;DR: It is concluded that education may modify the risk of cognitive decline in Parkinson's disease, and Protective effects of educational attainment, independent of dementia etiology, may be due to greater functional brain reserve.
Abstract: Cognitive deficits are common in Parkinson's disease (PD), but the pathophysiology and relationship to Alzheimer's disease (AD) are not understood. We used a case-control format to investigate putative risk factors for the development of dementia in patients with Parkinson's disease. We compared 52 cognitively intact patients with PD to 43 PD patients with dementia with regard to factors previously suggested as relevant to either AD or PD. Multiple logistic regression yielded the following significant predictors of dementia in PD: lack of education (less than a high school graduate) (OR 21); severity of motor deficit (UPDRS total motor score greater than 20; OR 6.34), and PD onset at greater than 60 years of age (OR 4.12). The predictive probability of dementia in our subjects when all three variables were positive was 97.9%. We conclude that education may modify the risk of cognitive decline in PD. Protective effects of educational attainment, independent of dementia etiology, may be due to greater functional brain reserve.
TL;DR: This review attempts to bring together concerns associated with various study designs and to integrate the conclusions from these studies, as well as identify a subgroup of patients at high risk for cognitive change following cardiac procedures.
TL;DR: To investigate the specificity of atrophic changes in the corpus callosum compared with the cerebellum and pons in patients with Alzheimer Disease, healthy elderly subjects, and a sample of prospectively studied subjects who have developed cognitive decline or “incipient dementia” (ID).
Abstract: OBJECTIVE: To investigate the specificity of atrophic changes in the corpus callosum (CC) compared with the cerebellum and pons in patients with Alzheimer Disease (AD), healthy elderly subjects (HE), and a sample of prospectively studied subjects who have developed cognitive decline or “incipient dementia” (ID).
DESIGN: Cross-sectional comparison by age using quantitative MRI.
SETTING: Ambulatory research unit.
PARTICIPANTS: Sixty HE subjects (mean age 78.2 years; range 66–95), 20 ID subjects (mean age 88.1 years; range 78–98) and 39 AD subjects (mean age 72.2 years; range 52–91) were enrolled in longitudinal studies of healthy aging or AD. The population was selected for optimal health; all were examined to exclude medical, neurological and psychiatric illnesses.
MEASUREMENTS: Brain atrophy by quantitative MRI.
RESULTS: AD subjects had smaller CC than HE or ID subjects, who did not differ from each other. All three sectors of the CC were smaller in AD than in HE or ID subjects. The cross sectional area of the cerebellum and pons did not differ between groups. HE and ID subjects showed a significant decline in CC size with age. No age-related decline was found for AD subjects. The regional atrophy of the CC in AD subjects was significantly related to cognitive function but not to disease duration.
CONCLUSIONS: Atrophy of the CC differentiates HE and ID from AD subjects and tracks the cognitive decline of this disease. In addition, optimally healthy subjects show an age-related decline in callosum size. The atrophy is specific to the CC, a cortical projection system, and does not occur in cerebellum or pons.
TL;DR: The sequence of cognitive decline, from unifunctional to global deficits, conforms to the three‐stage development of neurofibrillary tangles described by Braak and Braak.
Abstract: In the preclinical stage of Alzheimer's disease (AD), studies of asymptomatic mutation carriers have identified impairments in episodic memory. Other cognitive functions show no or slight impairment suggesting that preclinical AD is a unifunctional cognitive syndrome; the brain is affected selectively and predominantly in the medial temporal structures. In the early clinical stage, deficits occur in episodic memory, verbal abilities, visuospatial functions, attention, and executive functions. AD becomes a multifunctional cognitive syndrome and the brain's association cortices are affected. Nevertheless, sensory-motor performance and procedural memory seem to be intact and only slight impairment may be seen in primary memory. In advanced AD, cognitive dysfunction including deficits is global in primary memory, although sensory-motor performance may be well preserved. The brain's association cortices are severely affected. The sequence of cognitive decline, from unifunctional to global deficits, conforms to the three-stage development of neurofibrillary tangles described by Braak and Braak.
TL;DR: Citicoline therapy improved verbal memory functioning in older individuals with relatively inefficient memories and may prove effective in treating age-related cognitive decline that may be the precursor of dementia.
Abstract: Objective: To test the verbal memory of older volunteers given citicoline. Design: A randomized, double-blind, placebo-controlled, parallel group design was employed in the initial study. After data analysis, a subgroup was identified whose members had relatively inefficient memories. These subjects were recruited for a second study that used a crossover design. The subjects took either placebo or citicoline, 1000 mg/d, for 3 months in the initial study. In the crossover study, subjects took both placebo and citicoline, 2000 mg/d, each for 2 months. Subjects: The subjects were 47 female and 48 male volunteers 50 to 85 years old. They were screened for dementia, memory disorders, and other neurological problems. Of the subjects with relatively inefficient memories, 32 participated in the crossover study. Main Outcome Measure: Verbal memory was tested at each study visit using a logical memory passage. Plasma choline concentrations were measured at baseline; at days 30, 60, and 90 in the initial study; and at day 60 of each treatment condition in the crossover study. Plasma choline concentrations and memory scores were analyzed using repeated-measures analysis of variance and covariance, followed by planned comparisons when appropriate. Results: In the initial study, citicoline therapy improved delayed recall on logical memory only for the subjects with relatively inefficient memories. In the cross-over study, the higher dosage of citicoline was clearly associated with improved immediate and delayed logical memory. Conclusions: Citicoline therapy improved verbal memory functioning in older individuals with relatively inefficient memories. Citicoline may prove effective in treating age-related cognitive decline that may be the precursor of dementia.
TL;DR: The lack of correlation between disease severity and psychiatric disturbances indicates that psychiatric disorders progress nonlinearly, possibly because of differential degeneration of the striatal-cortical circuits.
Abstract: Objectives: To investigate the hypothesis that psychiatric disturbances in Huntington's disease are related to degree of cognitive or motor compromise and to determine correlations between CAG repeat length within the gene for Huntington's disease and disease severity. Design: Consecutive series of patients with Huntington's disease. Setting: Neurological specialty hospital. Patients: Seventeen men and 12 women from 24 families. Main Outcome Measures: The Hamilton Psychiatric and Anxiety Rating Scales and Brief Psychiatric Rating Scale were used to assess psychiatric disturbances; Folstein's Quantified Neurological Examination to evaluate motor status; and the Mini-Mental State Examination, Raven Progressive Matrices), Phonemic Verbal Fluency Test, Short Tale Test, Visual Search Test, and Benton's Visual Orientation Line Test to evaluate cognitive function. The length of the CAG repeat sequence in the Huntington's gene was determined by quantitative polymerase chain reaction. Results: Cognitive test scores correlated significantly with each other; of these, results of the Visual Search and Short Tale tests correlated significantly with the Folstein's Quantified Neurological Examination score ( P =.05 and P =.03, respectively). Results of the Folstein's Quantified Neurological Examination also correlated with the illness duration and the length of the CAG repeat. Although psychiatric scores correlated significantly among themselves ( P Conclusions: The lack of correlation between disease severity and psychiatric disturbances indicates that psychiatric disorders progress nonlinearly, possibly because of differential degeneration of the striatal-cortical circuits; the possibility that psychiatric disorders are prevalent in certain families with a member who has Huntington's disease is being further investigated. The lack of correlation between CAG length and cognitive and psychiatric variables needs further investigation.
TL;DR: The value of the Clock Drawing Test in predicting cognitive deterioration over a 4‐year period is evaluated independent of baseline cognitive status evaluated by the Mini‐Mental State Examination (MMSE).
Abstract: OBJECTIVE: To evaluate the value of the Clock Drawing Test (CDT) in predicting cognitive deterioration over a 4-year period, independent of baseline cognitive status evaluated by the Mini-Mental State Examination (MMSE).
DESIGN: A preplanned analysis of data collected during the second (1991) and the third (1995) follow-up of the Italian rural cohorts of the FINE Study (Finland, Italy, the Netherlands Elderly).
SUBJECTS: Of the 427 men (mean age 77.6 ± 4.1 years; range 72–90 years) interviewed in 1991, 264 survived and were reinterviewed in 1995. The study population included 247 persons who were interviewed and received a complete cognitive evaluation in both 1991 and in 1995.
MEASUREMENTS: Cognitive assessment in 1991 included the MMSE, the Dementia Rating Scale (DRS), and the CDT. The CDT was classified as normal or pathological, based on previously established criteria. The MMSE and the DRS were repeated in 1995.
RESULTS: Independent of age and baseline MMSE score, subjects with pathological CDT compared with normal CDT had lower MMSE scores at follow-up (P < .01). These results were also confirmed by evaluating cognitive decline through its impact on change over time in daily life autonomy, as measured by the DRS (P < .01). Among persons scoring more than 21 on the MMSE, compared with persons with a normal CDT, those with pathological CDT performance were 5.4 (95%CI: 2.1–14.2) and 5.5 (95%CI: 1.6–19.6) times more likely to have a MMSE score below 21 and 18, respectively, 4 years later, independent of age and baseline MMSE score.
CONCLUSIONS: Findings suggest that the CDT identifies older persons at high risk of cognitive decline and adds prognostic information that supplements the standard MMSE test. J Am Geriatr Soc 44:1326–1331, 1996.
TL;DR: Urinary incontinence is associated with severe cognitive decline in pure AD but usually precedes severe mental failure in DLBD cases, which could be useful in differentiating these two dementing illnesses.
Abstract: Incontinence is a hallmark of dementia, but little is known about its inception in different types of dementing disease. We recorded the dates of onset of dementia and of urinary incontinence in 73 demented patients followed for 5.6 +/- 2.5 years. The pathologic diagnosis was Alzheimer's disease (AD) in 29 cases, diffuse Lewy body disease (DLBD) in 11 cases, AD with Lewy bodies (AD+LB) in 13 cases, and AD with vascular lesions (AD+VL) in 20 cases. The onset of urinary incontinence was significantly earlier in DLBD cases (3.2 +/- 1.4 years after dementia onset) than in AD (5.9 +/- 2.5), AD+LB (5.8 +/- 2.4), and AD+VL (6.5 +/- 2.3) (p < 0.01). At the onset of bladder incontinence, the mean score in the Extended Dementia Scale was significantly higher (i.e., cognition was better) in DLBD cases (109.3 +/- 70.8) than in AD (21.3 +/- 40.4), AD+LB (45.6 +/- 45.1), and AD+VL (39.2 +/- 54.9) cases (p < 0.01). Urinary incontinence is associated with severe cognitive decline in pure AD but usually precedes severe mental failure in DLBD cases. This temporal pattern of cognitive decline and incontinence could be useful in differentiating these two dementing illnesses.
TL;DR: Comparisons along the various criteria indicate that if the objective is to have a general index of dementia of the Alzheimer type, short tests are at least as good and sometimes better than the longer tests.
Abstract: Objective: To provide comparative evidence for a valid and practical measure of mental-status functioning that could be used in dementia clinics. Design: Five mental-status neuropsychological tools for dementia screening were administered to patients in a memory disorder clinic. These included the Mini-Mental State Examination, the Dementia Rating Scale, the 6-item derivative of the Orientation-Memory-Concentration Test, a short Mental Status Questionnaire, and a composite tool we labeled the Ottawa Mental Status Examination, which assessed orientation, memory, attention, language, and visual-constructive functioning. The tools were compared using various criteria, including the statistical factors of sensitivity and reliability; effects of gender, native language, and language of testing; the utility of these tests for the differential diagnosis of Alzheimer-type and vascular dementia; and sensitivity to cognitive decline in the entire sample and among patients with severe dementia. Results: All of the tests were highly intercorrelated, suggesting that they are interchangeable. Conclusion: The comparisons along the various criteria indicate that if the objective is to have a general index of dementia of the Alzheimer type, short tests are at least as good and sometimes better than the longer tests.
TL;DR: Chronic PBN treatment improved the cognitive performance of aged rats in several tasks, resulted in greater survival during the treatment period, and decreased oxidative damage within brain areas important for cognitive function, suggesting that synthetic brain antioxidants could be developed to treat or prevent age-associated cognitive impairment and Alzheimer's disease.
TL;DR: The final multivariate analysis indicated that the following characteristics predicted more rapid cognitive decline: more education, history of dementia in a first degree relative, non-right handedness, better performances of Boston Naming Test, Gollin Incomplete Figures Test, and Benton Visual Retention Test-Delay, and worse performances on Responsive Naming test.