Three-year changes in cognitive performance as a function of apolipoprotein E genotype: Evidence from very old adults without dementia.

This study examined whether baseline cognitive performance and 3-year longitudinal changes were influenced by apolipoprotein E ε4 (APOE-ε4) allele. Participants consisted of 20 APOE-ε4 (2 ε2/ε4; 17 ε3/ε4; 1 ε4/ε4) and 54 non-ε4 (12 ε2/ε3; 42 ε3/ε3) very old adults without dementia (M?=?81.82?±?5.06 years) participating in a population-based longitudinal study. Cognitive performance was indexed by the Mini-Mental State Examination and multiple indexes of memory, visuospatial, and verbal performance. The results indicated no significant baseline differences between the 2 APOE groups in any cognitive performance measure. However, analyses revealed that the APOE-ε4 group experienced greater negative change in recognition memory for faces and words. Changes in tasks assessing other abilities did not vary as a function of APOE status. The authors concluded that APOE-ε4 status may not influence cognitive performance in adults without dementia and speculated that when such effects do occur (e.g., decline in recognition memory), these may be related to impending dementia, rather than to the influence of the specific genotype on cognition in normal aging. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of Apolipoprotein E Genotype on Spatial Attention, Working Memory, and Their Interaction in Healthy, Middle-Aged Adults: Results From the National Institute of Mental Health's BIOCARD Study.

The cognitive consequences of the apolipoprotein E-ε4 (APOE-ε4) allele were examined in middle age, before likely onset of symptoms of Alzheimer's disease. The authors identified 3 cognitive processes--visuospatial attention, spatial working memory, and the effect of visuospatial attention on working memory--and devised "behavioral assays" of the integrity of components of these processes. Redirecting visuospatial attention, retention of memory for location, and attentional modulation of memory of target location were affected by APOE genotype. Visuospatial attention showed additive effects of ε4 gene dose; each additional ε4 allele inherited further slowed disengagement from invalidly cued space. In contrast, working memory performance was affected only in ε4 homozygotes. Effect sizes for the APOE gene were moderate to large, ranging from 14% to 24%. Effects of APOE genotype on component processes of cognition in healthy, middle-aged adults is consistent with the emergence in adulthood of an APOE-ε4 cognitive phenotype. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Scaling of visuospatial attention undergoes differential longitudinal change as a function of APOE genotype prior to old age: Results from the NIMH BIOCARD Study.

The effect of apolipoprotein E (APOE) genotype on longitudinal cognitive decline in midlife was investigated with attentional scaling. Healthy individuals (mean age 59.6 years) genotyped for APOE were tested at 3 12-month intervals on a cued visual search task. A random effects model revealed significant interaction in effect of precue size on search speed between APOE-ε4 gene dose and assessment, with longitudinal increases in noncarriers and heterozygotes but longitudinal decreases in homozygotes. Association of APOE-ε4 with cognitive decline in midlife is consistent with an Alzheimer's disease (AD) prodrome, albeit a decade or more before average age of AD diagnosis. However, cognitive decline in midlife associated with a gene modulating neuronal response to insult argues that the concept of an AD prodrome includes factors that allow as well as cause AD. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Is the apolipoprotein e genotype a biomarker for mild cognitive impairment? Findings from a nationally representative study.

Objective: Although the ε4 allele of the apolipoprotein E (APOE) genotype is a known risk factor for Alzheimer's dementia (AD), prior findings on whether it is also a risk factor for mild cognitive impairment (MCI) have been inconsistent. We tested two contrasting explanations: (a) an ε4-AD specificity hypothesis, and (b) a measurement insensitivity hypothesis. Method: The frequency of the ε4 allele was investigated in older adults (mean age > 70) with various types of cognitive impairment (including MCI) and various types of dementia (including AD) with the aging, demographics, and memory study (ADAMS) of the National Institute on Aging's Health and Retirement Study (HRS). The ADAMS controls sources of Type I and Type II error that are posited in the ε4-AD specificity hypothesis and the measurement insensitivity hypothesis, and it is the only nationally representative data set on aging and cognitive impairment. Results: ε4 was a reliable predictor of MCI, with a frequency of 32% in MCI subjects versus 20% in healthy control subjects. This link was specific to MCI because ε4 was not a risk factor for other forms of cognitive impairment without dementia. Conclusions: The results support the measurement insensitivity hypothesis rather than the ε4-AD specificity hypothesis and are consistent with recent research showing modest reductions in cognitive performance among normal functioning ε4 carriers. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Influences of APOE ε4 and expertise on performance of older pilots.

Little is known about how APOE ε4-related differences in cognitive performance translate to real-life performance, where training and experience may help to sustain performance. We investigated the influences of APOE ε4 status, expertise (FAA pilot proficiency ratings), and their interaction on longitudinal flight simulator performance. Over a 2-year period, 139 pilots aged 42–69 years were tested annually. APOE ε4 carriers had lower memory performance than noncarriers (p = .019). APOE interacted with Expertise (p = .036), such that the beneficial influence of expertise (p = .013) on longitudinal flight simulator performance was more pronounced for ε4 carriers. Results suggest that relevant training and activity may help sustain middle-aged and older adults' real-world performance, especially among APOE ε4 carriers. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Neuropsychological function and apolipoprotein E genotype in the preclinical detection of Alzheimer's disease.

Nondemented older adults genotyped for the Apolipoprotein E (ApoE) ε4 allele (n?=?43) were neuropsychologically compared to participants without a copy of the ε4 allele (n?=?90). At baseline, the groups did not differ on age, education, gender, or global cognitive status. ApoE-ε4 participants demonstrated significantly poorer mean performances on delayed recall, but no significant group differences emerged on attention, language, constructional skills, psychomotor speed, or executive function. Significantly more ApoE-ε4 participants developed probable or questionable Alzheimer's disease (AD) compared with non-ε4 participants, suggesting that the group differences resulted from a preponderance of preclinical AD cases within the ε4 group and not from a direct influence of ApoE genotype on cognition. Cox proportional hazards analysis, adjusting for age, years of education, and global cognitive status, revealed that ApoE-ε4 allele status and measures of recall performance were significant and independent predictors of conversion to AD. Results support the importance of specific episodic memory changes and possession of the ApoE-ε4 allele in the preclinical detection of AD. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Change in cognitive functioning associated with ApoE genotype in a community sample of older adults.

The influence of a genetic risk factor, apolipoprotein E (apoE) ε4 variant, was assessed in older adults aged 70 to 94 on 3 occasions over 7 years. The results of latent growth curve analyses are reported for individuals genotyped for apoE at the 2nd measurement occasion (n = 601) and for a subsample of individuals without probable or definite dementia during the 1st or 2nd occasion (n = 434). ApoE-ε4 status was a significant predictor of level and change in memory performance and change in speed performance in the full sample, and of initial level and change in memory performance in the nondemented subsample. These results support previous findings that apoE-ε4 is associated with accelerated memory deterioration in individuals without clinical dementia. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The influence of apoe status on episodic and semantic memory: Data from a population-based study.

In a prospective cohort study, the authors demonstrated a more pronounced ε4-related deficit for participants 70 years of age and older in tasks assessing episodic recall. Apolipoprotein E (APOE) and age interacted for episodic memory tasks, whereas the interaction for semantic memory tasks was between APOE and test wave. Heterozygotes of ε4 between middle-age and young-old participants performed at a higher level than noncarriers of this allele in recall tasks. A dose effect was found such that carriers of 2 ε4 alleles failed more profoundly in acquiring and recollecting episodic information than carriers of 1 ε4 allele, who in turn failed more than carriers of non-ε4 alleles. The pattern of findings observed for older ε4 carriers suggests that these individuals have particular difficulty when the executive task demands are high. Several factors (e.g., smaller hippocampal volumes, less effective neural repair mechanisms) may account for these findings. On the basis of the data obtained, the authors argue that analyses of the effect of specific genes in cognition should be accompanied by assessment of performance at a specific level, with due attention to the individual's age. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Apolipoprotein E and Prospective Memory in Normally Aging Adults.

The ε4 allele of apolipoprotein E (APOE) is an established risk factor for Alzheimer's disease, despite uncertainty as to its effect on cognitive function in normal aging. Some evidence suggests poor episodic memory and executive functioning in ε4 allele carriers. Prospective memory has been overlooked in investigations of the relationship between APOE and cognition. The authors used a laboratory paradigm to examine the relationship between prospective memory and APOE status in healthy elderly adults, and they varied the association (high vs. low) between a target word and a response word. The authors found a significant deficit in prospective memory for ε4 allele carriers but no effect of association in either group. The results suggest the deficit was due to failure of the prospective component of the task. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Prospective memory and apolipoprotein e in healthy aging and early stage Alzheimer's disease.

The present study examined whether prospective memory performance discriminates healthy aging from very mild dementia of the Alzheimer type (DAT) and individuals at risk for DAT because of the presence of the apolipoprotein E (ApoE) ε4 allele. Four groups (young subjects, young-old control subjects, old-old control subjects, and subjects with very mild DAT) engaged in an event-based prospective memory task wherein they responded to a specific word embedded in a general knowledge test. Results indicated that prospective memory performance was clearly impaired in the very mild DAT group relative to the healthy older control groups. Moreover, prospective memory performance appears to capture unique variance in discriminating these 2 groups above and beyond standard retrospective memory tests. However, prospective memory was not affected by ApoE status in the young-old control group and, contrary to predictions, the ε4+ old-old control subjects showed better performance than did the ε4- subjects. In contrast to the healthy individuals, in the very mild DAT group, ε4+ subjects showed deficits in performance relative to the ε4- subjects. Discussion focuses on prospective memory as a cognitive indicator of early stage DAT. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hemispheric asymmetry reduction in older adults: The HAROLD model.

A model of the effects of aging on brain activity during cognitive performance is introduced. The model is called HAROLD (hemispheric asymmetry reduction in older adults), and it states that, under similar circumstances, prefrontal activity during cognitive performances tends to be less lateralized in older adults than in younger adults. The model is supported by functional neuroimaging and other evidence in the domains of episodic memory, semantic memory, working memory, perception, and inhibitory control. Age-related hemispheric asymmetry reductions may have a compensatory function or they may reflect a dedifferentiation process. They may have a cognitive or neural origin, and they may reflect regional or network mechanisms. The HAROLD model is a cognitive neuroscience model that integrates ideas and findings from psychology and neuroscience of aging. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Genetic and vascular modifiers of age-sensitive cognitive skills: Effects of COMT, BDNF, ApoE, and hypertension.

Several single nucleotide polymorphisms have been linked to neural and cognitive variation in healthy adults. We examined contribution of three polymorphisms frequently associated with individual differences in cognition (Catechol-O-Methyl-Transferase Val158Met, Brain-Derived-Neurotrophic-Factor Val66Met, and Apolipoprotein E ?4) and a vascular risk factor (hypertension) in a sample of 189 volunteers (age 18-82). Genotypes were determined from buccal culture samples, and cognitive performance was assessed in 4 age-sensitive domains?fluid intelligence, executive function (inhibition), associative memory, and processing speed. We found that younger age and COMT Met/Met genotype, associated with low COMT activity and higher prefrontal dopamine content, were independently linked to better performance in most of the tested domains. Homozygotes for Val allele of BDNF polymorphism exhibited better associative memory and faster speed of processing than the Met allele carriers, with greater effect for women and persons with hypertension. Carriers of ApoE ε4 allele evidenced steeper age-related increase in costs of Stroop color interference, but showed no negative effects on memory. The findings indicate that age-related cognitive performance is differentially affected by distinct genetic factors and their interactions with vascular health status. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Academic Performance, Career Potential, Creativity, and Job Performance: Can One Construct Predict Them All?

This meta-analysis addresses the question of whether 1 general cognitive ability measure developed for predicting academic performance is valid for predicting performance in both educational and work domains. The validity of the Miller Analogies Test (MAT; W. S. Miller, 1960) for predicting 18 academic and work-related criteria was examined. MAT correlations with other cognitive tests (e.g., Raven's Matrices [J. C. Raven, 1965]; Graduate Record Examinations) also were meta-analyzed. The results indicate that the abilities measured by the MAT are shared with other cognitive ability instruments and that these abilities are generalizably valid predictors of academic and vocational criteria, as well as evaluations of career potential and creativity. These findings contradict the notion that intelligence at work is wholly different from intelligence at school, extending the voluminous literature that supports the broad importance of general cognitive ability (g). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The apolipoprotein E gene, attention, and brain function.

The ε4 allele of the apolipoprotein E (ApoE) gene is associated with alterations in brain function and is a risk factor for Alzheimer's disease (AD). Changes in components of visuospatial attention with ApoE-ε4, aging, and AD are described. Healthy middle-aged adults without dementia who have the ApoE-ε4 gene show deficits in spatial attention and working memory that are qualitatively similar to those seen in clinically diagnosed AD patients. The findings support an association between ApoE polymorphism and specific components of visuospatial attention. Molecular mechanisms that may mediate the ApoE-attention link by modulating cholinergic neurotransmission to the posterior parietal cortex are discussed. Studies of attention and brain function in ApoE-ε4 carriers without dementia can advance knowledge of the genetics of visual attention, may enhance understanding of the preclinical phase of AD, and may lead to better methods for early AD detection. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cognitive engagement and cognitive aging: Is openness protective?

The purpose of this study was to examine whether openness to experience is related to longitudinal change in cognitive performance across advancing age. Participants were 857 individuals from the Swedish Adoption/Twin Study of Aging (SATSA). Factors for 5 cognitive domains were created, including verbal ability, spatial ability, memory, processing speed, and a global score, g. Latent growth curve models were used to assess level and longitudinal trajectories of cognitive performance. It was hypothesized that individuals who endorsed higher levels of openness would have higher cognitive test scores and lesser rates of cognitive decline. As predicted, higher openness to experience was associated with significantly higher performance across all cognitive tests for both men and women even after adjusting for education, cardiovascular disease, and activities of daily living. Openness, however, was not predictive of differences in the trajectories of cognitive performance over age. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neurocognitive markers of cognitive impairment: Exploring the roles of speed and inconsistency.

A well-known challenge for research in the cognitive neuropsychology of aging is to distinguish between the deficits and changes associated with normal aging and those indicative of early cognitive impairment. In a series of 2 studies, the authors explored whether 2 neurocognitive markers, speed (mean level) and inconsistency (intraindividual variability), distinguished between age groups (64-73 and 74-90+ years) and cognitive status groups (nonimpaired, mildly impaired, and moderately impaired). Study 1 (n = 416) showed that both level and inconsistency distinguished between the age and 2 cognitive status (not impaired, mildly impaired) groups, with a modest tendency for inconsistency to predict group membership over and above mean level. Study 2 (n = 304) replicated these results but extended them because of the qualifying effects associated with the unique moderately impaired oldest group. Specifically, not only were the groups more firmly distinguished by both indicators of speed, but evidence for the differential contribution of performance inconsistency was stronger. Neurocognitive markers of speed and inconsistency may be leading indicators of emerging cognitive impairment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Stress-related cognitive interference predicts cognitive function in old age.

Both subjective distress and cognitive interference have been proposed as mechanisms underlying the negative effects of stress on cognition. Studies of aging have shown that distress is associated with lower cognitive performance, but none have examined the effects of cognitive interference. One hundred eleven older adults (Mage=80) completed measures of working memory, processing speed, and episodic memory as well as self-report measures of subjective distress and cognitive interference. Cognitive interference was strongly associated with poorer performance on all 3 cognitive constructs, whereas distress was only modestly associated with lower working memory. The results suggest that cognitive process related to stress is an important predictor of cognitive function in advanced age. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Intraindividual variability is related to cognitive change in older adults: Evidence for within-person coupling.

In this study, the authors addressed the longitudinal nature of intraindividual variability over 3 years. A sample of 304 community-dwelling older adults, initially between the ages of 64 and 92 years, completed 4 waves of annual testing on a battery of accuracy- and latency-based tests covering a wide range of cognitive complexity. Increases in response-time inconsistency on moderately and highly complex tasks were associated with increasing age, but there were significant individual differences in change across the entire sample. The time-varying covariation between cognition and inconsistency was significant across the 1-year intervals and remained stable across both time and age. On occasions when intraindividual variability was high, participants' cognitive performance was correspondingly low. The strength of the coupling relationship was greater for more fluid cognitive domains such as memory, reasoning, and processing speed than for more crystallized domains such as verbal ability. Variability based on moderately and highly complex tasks provided the strongest prediction. These results suggest that intraindividual variability is highly sensitive to even subtle changes in cognitive ability. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cognitive estimation impairment in Alzheimer disease and mild cognitive impairment.

Intact executive functioning is believed to be required for performance on tasks requiring cognitive estimations. This study used a revised version of a cognitive estimations test (CET) to investigate whether patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) were impaired on the CET compared with normal elderly controls (NECs). Neuropsychological tests were administered to determine the relationship between CET performance and other cognitive domains. AD patients displayed impaired CET performance when compared with NECs but MCI patients did not. Negative correlations between tests of working memory (WM) and semantic memory and the CET were found in NECs and AD patients, indicating that these cognitive domains were important for CET performance. Regression analysis suggests that AD patients were unable to maintain semantic information in WM to perform the task. The authors conclude that AD patients display deficits in working memory, semantic memory, and executive function, which are required for adequate CET performance. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Genetic variance in processing speed drives variation in aging of spatial and memory abilities.

Previous analyses have identified a genetic contribution to the correlation between declines with age in processing speed and higher cognitive abilities. The goal of the current analysis was to apply the biometric dual change score model to consider the possibility of temporal dynamics underlying the genetic covariance between aging trajectories for processing speed and cognitive abilities. Longitudinal twin data from the Swedish Adoption/Twin Study of Aging, including up to 5 measurement occasions covering a 16-year period, were available from 806 participants ranging in age from 50 to 88 years at the 1st measurement wave. Factors were generated to tap 4 cognitive domains: verbal ability, spatial ability, memory, and processing speed. Model-fitting indicated that genetic variance for processing speed was a leading indicator of variation in age changes for spatial and memory ability, providing additional support for processing speed theories of cognitive aging. (PsycINFO Database Record (c) 2010 APA, all rights reserved)