Janine M. Jennings

Age-Related Differences in Neural Activity during Memory Encoding and Retrieval: A Positron Emission Tomography Study

Positron emission tomography (PET) was used to compare regional cerebral blood flow (rCBF) in young (mean 26 years) and old (mean 70 years) subjects while they were encoding, recognizing, and recalling word pairs. A multivariate partial-least-squares (PLS) analysis of the data was used to identify age-related neural changes associated with (1) encoding versus retrieval and (2) recognition versus recall. Young subjects showed higher activation than old subjects (1) in left prefrontal and occipito-temporal regions during encoding and (2) in right prefrontal and parietal regions during retrieval. Old subjects showed relatively higher activation than young subjects in several regions, including insular regions during encoding, cuneus/precuneus regions during recognition, and left prefrontal regions during recall. Frontal activity in young subjects was left-lateralized during encoding and right-lateralized during recall [hemispheric encoding/retrieval asymmetry (HERA)], whereas old adults showed little frontal activity during encoding and a more bilateral pattern of frontal activation during retrieval. In young subjects, activation in recall was higher than that in recognition in cerebellar and cingulate regions, whereas recognition showed higher activity in right temporal and parietal regions. In old subjects, the differences in blood flow between recall and recognition were smaller in these regions, yet more pronounced in other regions. Taken together, the results indicate that advanced age is associated with neural changes in the brain systems underlying encoding, recognition, and recall. These changes take two forms: (1) age-related decreases in local regional activity, which may signal less efficient processing by the old, and (2) age-related increases in activity, which may signal functional compensation.

Automatic versus intentional uses of memory : aging, attention and control

In 2 experiments, the authors used a process dissociation procedure (Jacoby, 1991) to separately examine the effects of aging on automatic and consciously controlled memory processes. In Experiment 1, a group of young adults in either a full-attention or divided-attention condition were compared with a group of elderly adults on a fame judgment task. Both age and divided attention had a detrimental effect on consciously controlled memory processing but left automatic processing intact. In Experiment 2, the same age-related pattern was found using a more demanding forced-choice recognition paradigm.

An opposition procedure for detecting age-related deficits in recollection: telling effects of repetition.

In 2 experiments, the advantages of placing automatic and consciously controlled memory processes in opposition to study age-related declines in memory performance were examined. Drawing on the common memory failure of mistakenly repeating oneself, a task was designed in which participants had to rely on conscious memory (recollection) to avoid repetition errors. Recollection proved to be severely affected by aging; older adults showed significantly more repetition errors than did younger adults, even at very short retention intervals. These results contrast sharply with the small age differences found with a standard recognition test. Moreover, L. L. Jacobys (1991) process-dissociation procedure (Experiment 2) showed that automatic memory processes were unaffected with age and could support recognition performance in older adults. The advantages of the opposition procedure for studying memory in older adults relative to other measures are discussed.

Recollection- and Familiarity-Based Memory in Healthy Aging and Amnestic Mild Cognitive Impairment

Little is known about the cognitive mechanisms of the memory impairment associated with amnestic mild cognitive impairment (aMCI). We explored recollection and familiarity in 27 healthy young adults, 45 healthy older adults, and 17 individuals with aMCI. Relative to the younger adults, recollection was reduced in the older adults, especially among those with aMCI. Familiarity did not differ among groups. In the healthy younger and older adults, better performance on a set of clinical memory measures that are sensitive to medial temporal lobe functioning was associated with greater recollection. In addition, among the healthy older adults better executive functioning was also associated with greater recollection. These results are consistent with the notion that recollection is a product of strategic processes mediated by the prefrontal cortex that suppport the retrieval of context-dependent memories from the hippocampus. Hippocampal atrophy associated with aMCI may disrupt this brain network, and thereby interfere with recollection.

Effect of a 24-Month Physical Activity Intervention vs Health Education on Cognitive Outcomes in Sedentary Older Adults: The LIFE Randomized Trial

IMPORTANCE Epidemiological evidence suggests that physical activity benefits cognition, but results from randomized trials are limited and mixed. OBJECTIVE To determine whether a 24-month physical activity program results in better cognitive function, lower risk of mild cognitive impairment (MCI) or dementia, or both, compared with a health education program. DESIGN, SETTING, AND PARTICIPANTS A randomized clinical trial, the Lifestyle Interventions and Independence for Elders (LIFE) study, enrolled 1635 community-living participants at 8 US centers from February 2010 until December 2011. Participants were sedentary adults aged 70 to 89 years who were at risk for mobility disability but able to walk 400 m. INTERVENTIONS A structured, moderate-intensity physical activity program (n = 818) that included walking, resistance training, and flexibility exercises or a health education program (n = 817) of educational workshops and upper-extremity stretching. MAIN OUTCOMES AND MEASURES Prespecified secondary outcomes of the LIFE study included cognitive function measured by the Digit Symbol Coding (DSC) task subtest of the Wechsler Adult Intelligence Scale (score range: 0-133; higher scores indicate better function) and the revised Hopkins Verbal Learning Test (HVLT-R; 12-item word list recall task) assessed in 1476 participants (90.3%). Tertiary outcomes included global and executive cognitive function and incident MCI or dementia at 24 months. RESULTS At 24 months, DSC task and HVLT-R scores (adjusted for clinic site, sex, and baseline values) were not different between groups. The mean DSC task scores were 46.26 points for the physical activity group vs 46.28 for the health education group (mean difference, -0.01 points [95% CI, -0.80 to 0.77 points], P = .97). The mean HVLT-R delayed recall scores were 7.22 for the physical activity group vs 7.25 for the health education group (mean difference, -0.03 words [95% CI, -0.29 to 0.24 words], P = .84). No differences for any other cognitive or composite measures were observed. Participants in the physical activity group who were 80 years or older (n = 307) and those with poorer baseline physical performance (n = 328) had better changes in executive function composite scores compared with the health education group (P = .01 for interaction for both comparisons). Incident MCI or dementia occurred in 98 participants (13.2%) in the physical activity group and 91 participants (12.1%) in the health education group (odds ratio, 1.08 [95% CI, 0.80 to 1.46]). CONCLUSIONS AND RELEVANCE Among sedentary older adults, a 24-month moderate-intensity physical activity program compared with a health education program did not result in improvements in global or domain-specific cognitive function. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01072500.

Acute effect of a high nitrate diet on brain perfusion in older adults

AIMS Poor blood flow and hypoxia/ischemia contribute to many disease states and may also be a factor in the decline of physical and cognitive function in aging. Nitrite has been discovered to be a vasodilator that is preferentially harnessed in hypoxia. Thus, both infused and inhaled nitrite are being studied as therapeutic agents for a variety of diseases. In addition, nitrite derived from nitrate in the diet has been shown to decrease blood pressure and improve exercise performance. Thus, dietary nitrate may also be important when increased blood flow in hypoxic or ischemic areas is indicated. These conditions could include age-associated dementia and cognitive decline. The goal of this study was to determine if dietary nitrate would increase cerebral blood flow in older adults. METHODS AND RESULTS In this investigation we administered a high vs. low nitrate diet to older adults (74.7±6.9 years) and measured cerebral perfusion using arterial spin labeling magnetic resonance imaging. We found that the high nitrate diet did not alter global cerebral perfusion, but did lead to increased regional cerebral perfusion in frontal lobe white matter, especially between the dorsolateral prefrontal cortex and anterior cingulate cortex. CONCLUSION These results suggest that dietary nitrate may be useful in improving regional brain perfusion in older adults in critical brain areas known to be involved in executive functioning.

Improving memory in older adults: Training recollection

We explore a novel theory‐guided approach for training memory in older adults that distinguishes between recollection and automatic influences. Participants were given multiple trials of a continuous recognition task in which they had to use recollection to identify repeated items. After each correct trial, the number of intervening items between repetitions was gradually increased (incremented‐difficulty approach). Initially, accurate identification only occurred with two intervening items, which increased to 28 items following 6 hours of training. A second group of participants was given an equal amount of practice with the task but the number of intervening items was varied randomly across trials, independent of accuracy. These individuals showed significantly smaller gains in recollection. Results suggest that an incremented‐difficulty approach can enhance the ability to recollect information across increasing delay intervals. Implications for future training efforts are discussed.

Recollection training and transfer effects in older adults: successful use of a repetition-lag procedure.

Abstract We examined an approach aimed at training consciously-controlled recollection, introduced by Jennings and Jacoby (2003), for its ability to replicate and generalize. A continuous recognition task, requiring recollection to identify the occurrence of repeated items over gradually increasing lag intervals (number of intervening items between the first and second presentation of a repeated word), was given to a group of older adults twice a week for three weeks. Pre-and-post training performance was assessed on multiple measures and compared with a recognition practice and no contact control group. Recollection training proved successful; accurate identification of repeated items increased across a lag interval of 2 to 18 intervening items. Post-training gains following recollection training were found on n-back, self-ordered pointing, source discrimination and digit symbol substitution, but not with reading span or the CVLT-II. No changes were identified in the other groups. Gains from recollection training seem to transfer successfully in older adults.

Age-Related Changes and the Attention Network Task: An Examination of Alerting, Orienting, and Executive Function

ABSTRACT The effects of aging on alerting, orienting, and executive function were examined with the use of the Attention Network Task, which combines the Posner spatial cuing task and the Eriksen flanker task into a single procedure. We found that older adults showed significantly less alerting than young adults in response to a warning cue, although there were no age differences in orienting or executive function once processing speed was taken into account. We suggest that age differences in alerting may depend in part upon the presentation duration or persistence of the warning cue.

Designing clinical trials for assessing the effects of cognitive training and physical activity interventions on cognitive outcomes: The Seniors Health and Activity Research Program Pilot (SHARP-P) Study, a randomized controlled trial

BackgroundThe efficacy of non-pharmacological intervention approaches such as physical activity, strength, and cognitive training for improving brain health has not been established. Before definitive trials are mounted, important design questions on participation/adherence, training and interventions effects must be answered to more fully inform a full-scale trial.MethodsSHARP-P was a single-blinded randomized controlled pilot trial of a 4-month physical activity training intervention (PA) and/or cognitive training intervention (CT) in a 2 × 2 factorial design with a health education control condition in 73 community-dwelling persons, aged 70-85 years, who were at risk for cognitive decline but did not have mild cognitive impairment.ResultsIntervention attendance rates were higher in the CT and PACT groups: CT: 96%, PA: 76%, PACT: 90% (p=0.004), the interventions produced marked changes in cognitive and physical performance measures (p≤0.05), and retention rates exceeded 90%. There were no statistically significant differences in 4-month changes in composite scores of cognitive, executive, and episodic memory function among arms. Four-month improvements in the composite measure increased with age among participants assigned to physical activity training but decreased with age for other participants (intervention*age interaction p = 0.01). Depending on the choice of outcome, two-armed full-scale trials may require fewer than 1,000 participants (continuous outcome) or 2,000 participants (categorical outcome).ConclusionsGood levels of participation, adherence, and retention appear to be achievable for participants through age 85 years. Care should be taken to ensure that an attention control condition does not attenuate intervention effects. Depending on the choice of outcome measures, the necessary sample sizes to conduct four-year trials appear to be feasible.Trial RegistrationClinicaltrials.gov Identifier: NCT00688155