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)     

Are the memories of older adults positively biased?

There is disagreement in the literature about whether a "positivity effect" in memory performance exists in older adults. To assess the generalizability of the effect, the authors examined memory for autobiographical, picture, and word information in a group of younger (17-29 years old) and older (60-84 years old) adults. For the autobiographical memory task, the authors asked participants to produce 4 positive, 4 negative, and 4 neutral recent autobiographical memories and to recall these a week later. For the picture and word tasks, participants studied photos or words of different valences (positive, negative, neutral) and later remembered them on a free-recall test. The authors found significant correlations in memory performance, across task material, for recall of both positive and neutral valence autobiographical events, pictures, and words. When the authors examined accurate memories, they failed to find consistent evidence, across the different types of material, of a positivity effect in either age group. However, the false memory findings offer more consistent support for a positivity effect in older adults. During recall of all 3 types of material, older participants recalled more false positive than false negative memories. (PsycINFO Database Record (c) 2010 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)     

Apolipoprotein E and Cognitive Performance: A Meta-Analysis.

The ε4 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 ε4-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-ε4 group differences for global cognitive functioning, episodic memory, and executive functioning, in favor of non-ε4 carriers. In addition, older age and APOE-ε4 heterozygosity was associated with smaller ε4-related impairments. The meta-analysis results suggest that APOE-ε4 genotype does affect cognitive performance in healthy aging, although the influence is relatively small and specific to certain domains of cognitive performance. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Selective adult age differences in an age-invariant multifactor model of declarative memory.

Confirmatory factor analysis was used to test competing models of declarative memory. Data from middle-aged participants provided support for a model comprised of 2 2nd-order (episodic and semantic memory) and 4 1st-order (recall, recognition, fluency, and knowledge) factors. Extending this model across young-old and old-old participants established support for age invariance. Tests of group differences showed an age deficit in episodic memory that was more pronounced for recall than for recognition. For semantic memory, there was an increase in knowledge from middle to young-old age and thereafter a decrease. Overall, the results support the view that episodic memory is more age sensitive than semantic memory, but they also indicate that aging has differential effects within these 2 forms of memory. (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)     

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)     

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)     

Longitudinal change in cognitive performance among individuals with mild cognitive impairment.

The authors used mixed-effects growth models to examine longitudinal change in neuropsychological performance over a 4-year period among 197 individuals who were either normal or had mild cognitive impairment (MCI) at baseline. At follow-up, the participants were divided into 4 groups: (a) controls: participants who were normal at both baseline and follow-up (n = 33), (b) stables: participants with MCI whose Clinical Dementia Rating-Sum of Boxes (CDR-SB) score did not differ between the first and last evaluations (n = 22), (c) decliners: participants with MCI whose CDR-SB score declined between the first and last evaluations (n = 95), and (d) converters: participants who received a clinical diagnosis of Alzheimer's disease during the follow-up period (n = 47). Only the Episodic Memory factor showed a significantly greater rate of decline over the follow-up period among the converters. Two other factors were significantly lower in converters at baseline in comparison with other groups (the executive function factor and the general knowledge factor), but the rate of decline over time did not differ. Individuals with an APOE ε4 allele scored lower on the episodic memory and executive function factors at baseline. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Age differences in item manipulation span: The case of letter-number sequencing.

The authors report 2 experiments in which they examined age differences in working memory tasks involving complex item manipulation (i.e., letter-number sequencing). In Experiment 1, age differences on tasks involving item manipulation were not greater than age differences on tasks requiring recall of items in the order in which they appeared, suggesting that older adults do not have difficulty with item manipulation per se. In Experiment 2, slower presentation rates increased age differences in item manipulation spans, although age differences at the fastest rate may be attributed to differences in strategy use. In both experiments, age differences were largest when participants were most likely to be remembering familiar sequences, suggesting that older adults may have difficulties dampening the representations of such sequences once they are activated. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

APOE genotype and cognitive functioning in a large age-stratified population sample.

There is evidence that the cognitive effects of Alzheimer's disease can be seen decades before disease diagnosis. If this is the case, then the apolipoprotein E (APOE) *E4 allele might be expected to have effects on cognitive functioning earlier in the life span. To assess such effects, the authors examined data on the *E4 allele and cognitive functioning from a population sample of 6,560 Caucasians covering the age groups of 20-24, 40-44, and 60-64 years. Participants were assessed on tests of episodic memory, working memory, mental speed, reaction time, and reading vocabulary. Although performance on all tests except reading vocabulary declined across age groups, there was no effect of the APOE *E4 allele at any age. These results indicate that APOE *E4 does not have preclinical effects early in the life span on these cognitive functions. Cognitive aging effects between the ages of 20 and 64 years must not be due to preclinical Alzheimer's disease. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A Meta-Analytic Review of Prospective Memory and Aging.

A meta-analysis of prospective memory (PM) studies revealed that in laboratory settings younger participants outperform older participants on tests of both time- and event-based PM (rs=-.39 and -.34, respectively). Event-based PM tasks that impose higher levels of controlled strategic demand are associated with significantly larger age effects than event-based PM tasks that are supported by relatively more automatic processes (rs=-.40 vs. -.14, respectively). However, contrary to the prevailing view in the literature, retrospective memory as measured by free recall is associated with significantly greater age-related decline (r=-.52) than PM, and older participants perform substantially better than their younger counterparts in naturalistic PM studies (rs=.35 and .52 for event- and time-based PM, respectively). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Feeling of knowing in episodic memory following moderate to severe closed-head injury.

The ability to accurately monitor one's memory is a metacognitive process that is important in everyday life. The authors examined episodic memory feeling-of-knowing (FOK) ratings in 21 moderate to severe closed-head injury (CHI) participants (more than 1 year postinjury) and 21 controls. Participants studied 36 critical cue-target word pairs. Following a brief delay, they were asked to recall the target that corresponded to a given cue. Confidence ratings were made for recalled words, and FOK judgments were made for nonrecalled words in terms of the likelihood of recognizing the target word on a subsequent recognition test. CHI participants demonstrated less accurate recall but accurate ability to judge their recall performance (retrospective memory monitoring). They also demonstrated intact FOK judgments when providing binary judgments but demonstrated difficulties making finer discriminations on an ordinal scale (prospective memory monitoring). These findings suggest that memory monitoring is not a unitary construct. It is proposed that CHI participants may display intact memory monitoring when predictions are based on familiarity assessment but not when continued probing for additional episodic information is required. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The influence of levels of processing on recall from working memory and delayed recall tasks.

Recent research in working memory has highlighted the similarities involved in retrieval from complex span tasks and episodic memory tasks, suggesting that these tasks are influenced by similar memory processes. In the present article, the authors manipulated the level of processing engaged when studying to-be-remembered words during a reading span task (Experiment 1) and an operation span task (Experiment 2) in order to assess the role of retrieval from secondary memory during complex span tasks. Immediate recall from both span tasks was greater for items studied under deep processing instructions compared with items studied under shallow processing instructions regardless of trial length. Recall was better for deep than for shallow levels of processing on delayed recall tests as well. These data are consistent with the primary-secondary memory framework, which suggests that to-be-remembered items are displaced from primary memory (i.e., the focus of attention) during the processing phases of complex span tasks and therefore must be retrieved from secondary memory. (PsycINFO Database Record (c) 2011 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)     

Eyeblink Classical Conditioning to Auditory and Olfactory Stimuli: Performance Among Older Adults With and Without the Apolipoprotein E ε4 Allele.

Patients with Alzheimer's disease (AD) demonstrate slowed acquisition of the conditioned response (CR) in eyeblink classical conditioning paradigms (EBCC), although it is unknown how early in the course of the disease CR acquisition is affected. This study investigated whether changes in the rate of CR acquisition were apparent in nondemented older adults at greater genetic risk for developing AD (i.e., carriers of the apolipoprotein E [APOE] ε4 allele). Both ε4+ and ε4- participants demonstrated CR acquisition to auditory and olfactory CSs; however, rate of acquisition to the olfactory CS was significantly slower in ε4+ persons. Both groups acquired the CR to an auditory CS at the same rate. Results support olfactory compromise in the earliest stages of the AD disease process. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential effects of age on item and associative measures of memory: A meta-analysis.

In this meta-analysis, the authors evaluated recent suggestions that older adults' episodic memory impairments are partially due to a reduced ability to encode and retrieve associated/bound units of information. Results of 90 studies of episodic memory for both item and associative information in 3,197 young and 3,192 older adults provided support for the age-related associative/binding deficit suggestion, indicating a larger effect of age on memory for associative information than for item information. Moderators assessed included the type of associations, encoding instructions, materials, and test format. Results indicated an age-related associative deficit in memory for source, context, temporal order, spatial location, and item pairings, in both verbal and nonverbal material. An age-related associative deficit was quite pronounced under intentional learning instructions but was not clearly evident under incidental learning instructions. Finally, test format was also found to moderate the associative deficit, with older adults showing an associative/binding deficit when item memory was evaluated via recognition tests but not when item memory was evaluated via recall tests, in which case the age-related deficits were similar for item and associative information. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Apolipoprotein E Gene Variability and Cognitive Functions at Age 79: A Follow-Up of the Scottish Mental Survey of 1932.

Apolipoprotein E (APOE) genotype is a possible influence on nonpathological cognitive aging. The authors studied 462 community-dwelling, 79-year-old people born in 1921, whose childhood IQ had been assessed in the Scottish Mental Survey of 1932 (Scottish Council for Research in Education, 1933). Adjusting for sex, childhood IQ, and self-reported illnesses, the authors found that those with an APOE e4 allele had significantly lower Wechsler Logical Memory (D. Wechsler, 1987) scores than those without an e4 allele. Those people with APOE s2/e3 genotypes had significantly higher Wechsler Logical Memory scores than e3/s3, who were significantly higher than e3/e4. Neither nonverbal reasoning nor verbal fluency were affected. In this sample, APOE genotype contributed to verbal memory in old age. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

How many memory systems? Evidence from aging.

The present research tested Tulving's (1985) ternary memory theory. Young (ages 19–32) and older (ages 63–80) adults were given procedural, semantic, and episodic memory tasks. Repetition, lag, and codability were manipulated in a picture-naming task, followed by incidental memory tests. Relative to young adults, older adults exhibited lower levels of recall and recognition, but these episodic measures increased similarly as a function of lag and repetition in both age groups. No age-related deficits emerged in either semantic memory (vocabulary, latency slopes, naming errors and tip-of-the-tongue responses) or procedural memory (repetition priming magnitude and rate of decline). In addition to the age by memory task dissociations, the manipulation of codability produced slower naming latencies and more naming errors (semantic memory), yet promoted better recall and recognition (episodic memory). Finally, a factor analysis of 11 memory measures revealed three distinct factors, providing additional support for a tripartite memory model. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Working memory plasticity in old age: Practice gain, transfer, and maintenance.

Adult age differences in cognitive plasticity have been studied less often in working memory than in episodic memory. The authors investigated the effects of extensive working memory practice on performance improvement, transfer, and short-term maintenance of practice gains and transfer effects. Adults age 20-30 years and 70-80 years practiced a spatial working memory task with 2 levels of processing demands across 45 days for about 15 min per day. In both age groups and relative to age-matched, no-contact control groups, we found (a) substantial performance gains on the practiced task, (b) near transfer to a more demanding spatial n-back task and to numerical n-back tasks, and (c) 3-month maintenance of practice gains and near transfer effects, with decrements relative to postpractice performance among older but not younger adults. No evidence was found for far transfer to complex span tasks. The authors discuss neuronal mechanisms underlying adult age differences and similarities in patterns of plasticity and conclude that the potential of deliberate working memory practice as a tool for improving cognition in old age merits further exploration. (PsycINFO Database Record (c) 2010 APA, all rights reserved)