The APOE ∍4 allele Is Associated with Decline on Delayed Recall Performance in Community-Dwelling Older Adults
01 Dec 1998-Journal of the American Geriatrics Society (Blackwell Publishing Ltd)-Vol. 46, Iss: 12, pp 1493-1498
TL;DR: This study investigated whether the Apolipoprotein (APOE) ∍4 allele was associated with cognitive decline in community‐dwelling older adults and found it was not.
Abstract: OBJECTIVE This study investigated whether the Apolipoprotein (APOE) epsilon4 allele was associated with cognitive decline in community-dwelling older adults. DESIGN Longitudinal cognitive performance of older adults with the epsilon3/epsilon4 genotype was compared with that of older adults with the epsilon3/epsilon3 genotype. SETTING Aging Clinical Research Center, Stanford University. PARTICIPANTS One hundred community-dwelling older adults were recruited from a pool of 531 individuals who had participated in a memory training study 4 to 5 years earlier. These individuals were concerned about their memory functioning and were recruited through newspaper advertisements and contacts with local senior centers. The 100 individuals who agreed to participate in the follow-up investigation were between 59 and 95 years of age. MEASUREMENTS At both baseline and follow-up, subjects were administered a battery of seven cognitive tests that examined verbal and spatial memory, attention, speed-of-processing, and language abilities. APOE genotype was determined at follow-up. RESULTS Individuals with the epsilon3/epsilon4 APOE genotype were significantly younger than individuals with the APOE epsilon3/epsilon3 genotype. No significant differences were observed between the two groups on measures of attention, speed-of-processing, vocabulary, immediate verbal memory, and immediate spatial memory. However, those older adults with the epsilon3/epsilon4 genotype exhibited significantly greater decline in performance on delayed recall of verbal material than did those with the epsilon3/epsilon3 APOE genotype. CONCLUSION These findings are consistent with previous studies, which suggest that the APOE epsilon4 allele predicts decline on measures of delayed recall.
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TL;DR: This paper attempts to develop a coherent theoretical account of reserve, a distinction is suggested between reserve, the ability to optimize or maximize normal performance, and compensation, an attempt to maximize performance in the face of brain damage by using brain structures or networks not engaged when the brain is not damaged.
Abstract: The idea of reserve against brain damage stems from the repeated observation that there does not appear to be a direct relationship between the degree of brain pathology or brain damage and the clinical manifestation of that damage. This paper attempts to develop a coherent theoretical account of reserve. One convenient subdivision of reserve models revolves around whether they envision reserve as a passive process, such as in brain reserve or threshold, or see the brain as actively attempting to cope with or compensate for pathology, as in cognitive reserve. Cognitive reserve may be based on more efficient utilization of brain networks or of enhanced ability to recruit alternate brain networks as needed. A distinction is suggested between reserve, the ability to optimize or maximize normal performance, and compensation, an attempt to maximize performance in the face of brain damage by using brain structures or networks not engaged when the brain is not damaged. Epidemiologic and imaging data that help to develop and support the concept of reserve are presented.
3,136 citations
Cites background from "The APOE ∍4 allele Is Associated wi..."
...For example, APOE influences the timing of the onset of AD, but also has been related to the rate of change in memory capacity in nondemented elders (O'Hara et al., 1998)....
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TL;DR: In this article, the effect of perioperative decline on long-term cognitive function after coronary-artery bypass grafting (CABG) surgery was investigated in 261 patients who underwent CABG, and neurocognitive tests were performed preoperatively (at base line), before discharge, and six weeks, six months, and five years after the surgery.
Abstract: Background Cognitive decline complicates early recovery after coronary-artery bypass grafting (CABG) and may be evident in as many as three quarters of patients at the time of discharge from the hospital and a third of patients after six months. We sought to determine the course of cognitive change during the five years after CABG and the effect of perioperative decline on long-term cognitive function. Methods In 261 patients who underwent CABG, neurocognitive tests were performed preoperatively (at base line), before discharge, and six weeks, six months, and five years after CABG surgery. Decline in postoperative function was defined as a drop of 1 SD or more in the scores on tests of any one of four domains of cognitive function. (A reduction of 1 SD represents a decline in function of approximately 20 percent.) Overall neurocognitive status was assessed with a composite cognitive index score representing the sum of the scores for the individual domains. Factors predicting long-term cognitive decline we...
1,717 citations
TL;DR: Patterns of brain activation during tasks requiring memory differ depending on the genetic risk of Alzheimer's disease and may predict a subsequent decline in memory.
Abstract: Background The e4 allele of the apolipoprotein E gene (APOE) is the chief known genetic risk factor for Alzheimer's disease, the most common cause of dementia late in life. To determine the relation between brain responses to tasks requiring memory and the genetic risk of Alzheimer's disease, we performed APOE genotyping and functional magnetic resonance imaging (MRI) of the brain in older persons with intact cognition. Methods We studied 30 subjects (age, 47 to 82 years) who were neurologically normal, of whom 16 were carriers of the APOE e4 allele and 14 were homozygous for the APOE e3 allele. The mean age and level of education were similar in the two groups. Patterns of brain activation during functional MRI scanning were determined while subjects memorized and recalled unrelated pairs of words and while subjects rested between such periods. Memory was reassessed in 14 subjects two years later. Results Both the magnitude and the extent of brain activation during memory-activation tasks in regions affe...
1,245 citations
TL;DR: It is suggested that APOE-epsilon4 genotype does affect cognitive performance in healthy aging, although the influence is relatively small and specific to certain domains of cognitive performance.
Abstract: The epsilon4 allele of the apolipoprotein E (APOE) gene is a known risk factor for Alzheimer's disease and may also affect cognitive performance in normal aging. Evidence of the presence and magnitude of epsilon4-related cognitive deficits was examined with a meta-analysis of the available literature. Thirty-eight studies were included, and cognitive performance was collapsed into 8 domains. Results indicated significant APOE-epsilon4 group differences for global cognitive functioning, episodic memory, and executive functioning, in favor of non-epsilon4 carriers. In addition, older age and APOE-epsilon4 heterozygosity was associated with smaller epsilon4-related impairments. The meta-analysis results suggest that APOE-epsilon4 genotype does affect cognitive performance in healthy aging, although the influence is relatively small and specific to certain domains of cognitive performance.
480 citations
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
References
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TL;DR: A simplified, scored form of the cognitive mental status examination, the “Mini-Mental State” (MMS) which includes eleven questions, requires only 5-10 min to administer, and is therefore practical to use serially and routinely.
76,181 citations
01 Jan 2002
TL;DR: The Mini-Mental State (MMS) as mentioned in this paper is a simplified version of the standard WAIS with eleven questions and requires only 5-10 min to administer, and is therefore practical to use serially and routinely.
Abstract: EXAMINATION of the mental state is essential in evaluating psychiatric patients.1 Many investigators have added quantitative assessment of cognitive performance to the standard examination, and have documented reliability and validity of the several “clinical tests of the sensorium”.2*3 The available batteries are lengthy. For example, WITHERS and HINTON’S test includes 33 questions and requires about 30 min to administer and score. The standard WAIS requires even more time. However, elderly patients, particularly those with delirium or dementia syndromes, cooperate well only for short periods.4 Therefore, we devised a simplified, scored form of the cognitive mental status examination, the “Mini-Mental State” (MMS) which includes eleven questions, requires only 5-10 min to administer, and is therefore practical to use serially and routinely. It is “mini” because it concentrates only on the cognitive aspects of mental functions, and excludes questions concerning mood, abnormal mental experiences and the form of thinking. But within the cognitive realm it is thorough. We have documented the validity and reliability of the MMS when given to 206 patients with dementia syndromes, affective disorder, affective disorder with cognitive impairment “pseudodementia”5T6), mania, schizophrenia, personality disorders, and in 63 normal subjects.
70,887 citations
TL;DR: The APOE-epsilon 4 allele is associated with the common late onset familial and sporadic forms of Alzheimer9s disease (AD) in 42 families with late onset AD.
Abstract: The apolipoprotein E type 4 allele (APOE-epsilon 4) is genetically associated with the common late onset familial and sporadic forms of Alzheimer9s disease (AD). Risk for AD increased from 20% to 90% and mean age at onset decreased from 84 to 68 years with increasing number of APOE-epsilon 4 alleles in 42 families with late onset AD. Thus APOE-epsilon 4 gene dose is a major risk factor for late onset AD and, in these families, homozygosity for APOE-epsilon 4 was virtually sufficient to cause AD by age 80.
8,669 citations
TL;DR: This work has used restriction isotyping (restriction enzyme isoform genotyping) for rapid typing of common apolipoprotein E isoforms (E2, E3, E4) and distinguished each of the isoforms by a unique combination of HhaI fragment sizes that enabled unambiguous typing of all homozygotic and heterozygotic combinations.
2,973 citations
TL;DR: In late middle age, cognitively normal subjects who are homozygous for the epsilon 4 allele for apolipoprotein E have reduced glucose metabolism in the same regions of the brain as in patients with probable Alzheimer's disease.
Abstract: Background Variants of the apolipoprotein E allele appear to account for most cases of late-onset Alzheimer's disease, and persons with two copies of the e4 allele appear to have an especially high risk of dementia. Positron-emission tomography (PET) has identified specific regions of the brain in which the rate of glucose metabolism declines progressively in patients with probable Alzheimer's disease. We used PET to investigate whether these same regions of the brain are affected in subjects homozygous for the e4 allele before the onset of cognitive impairment. Methods Apolipoprotein E genotypes were established in 235 volunteers 50 to 65 years of age who reported a family history of probable Alzheimer's disease. Neurologic and psychiatric evaluations, a battery of neuropsychological tests, magnetic resonance imaging, and PET were performed in 11 e4 homozygotes and 22 controls without the e4 allele who were matched for sex, age, and level of education. An automated method was used to generate an aggregat...
1,234 citations