Search

Background: Despite growing evidence regarding the association between exercise training (ET) and functional brain network connectivity, little is known about the effects of ET on large-scale within- and between-network functional connectivity (FC) of core brain networks. Objective: We investigated the effects of ET on within- and between-network functional connectivity of the default mode network (DMN), frontoparietal network (FPN), and salience network (SAL) in older adults with intact cognition (CN) and older adults diagnosed with mild cognitive impairment (MCI). The association between ET-induced changes in FC and cognitive performance was examined. Methods: 33 older adults (78.0±7.0 years; 16 MCI and 17 CN) participated in this study. Before and after a 12-week walking ET intervention, participants underwent a graded exercise test, Controlled Oral Word Association Test (COWAT), Rey Auditory Verbal Learning Test (RAVLT), a narrative memory test (logical memory; LM), and a resting-state fMRI scan. We examined the within (W) and between (B) network connectivity of the DMN, FPN, and SAL. We used linear regression to examine associations between ET-related changes in network connectivity and cognitive function. Results: There were significant improvements in cardiorespiratory fitness, COWAT, RAVLT, and LM after ET across participants. Significant increases in DMNW and SALW, and DMN-FPNB, DMN-SALB, and FPN-SALB were observed after ET. Greater SALW and FPN-SALB were associated with enhanced LM immediate recall performance after ET in both groups. Conclusion: Increased within- and between-network connectivity following ET may subserve improvements in memory performance in older individuals with intact cognition and with MCI due to Alzheimer’s disease.

Background: Exercise training (ET) has neuroprotective effects in the hippocampus, a key brain region for memory that is vulnerable to age-related dysfunction. Objective: We investigated the effects of ET on functional connectivity (FC) of the hippocampus in older adults with mild cognitive impairment (MCI) and a cognitively normal (CN) control group. We also assessed whether the ET-induced changes in hippocampal FC (Δhippocampal-FC) are associated with changes in memory task performance (Δmemory performance). Methods: 32 older adults (77.0±7.6 years; 16 MCI and 16 CN) participated in the present study. Cardiorespiratory fitness tests, memory tasks (Rey Auditory Verbal Learning Test (RAVLT) and Logical Memory Test (LM)), and resting-state fMRI were administered before and after a 12-week walking ET intervention. We utilized a seed-based correlation analysis using the bilateral anterior and posterior hippocampi as priori seed regions of interest. The associations of residualized ET-induced Δhippocampal-FC and Δmemory performance were assessed using linear regression. Results: There were significant improvements in RAVLT Trial 1 and LM test performance after ET across participants. At baseline, MCI, compared to CN, demonstrated significantly lower posterior hippocampal FC. ET was associated with increased hippocampal FC across groups. Greater ET-related anterior and posterior hippocampal FC with right posterior cingulate were associated with improved LM recognition performance in MCI participants. Conclusion: Our findings indicate that hippocampal FC is significantly increased following 12-weeks of ET in older adults and, moreover, suggest that increased hippocampal FC may reflect neural network plasticity associated with ET-related improvements in memory performance in individuals diagnosed with MCI.

Background: Body mass index (BMI) has been identified as an important modifiable lifestyle risk factor for dementia, but less is known about how BMI might interact with Apolipoprotein E ɛ4 (APOE ɛ4) carrier status to predict conversion to mild cognitive impairment (MCI) and dementia. Objective: The aim of this study was to investigate the interaction between APOE ɛ4 status and baseline (bBMI) and five-year BMI change (ΔBMI) on conversion to MCI or dementia in initially cognitively healthy older adults. Methods: The associations between bBMI, ΔBMI, APOE ɛ4 status, and conversion to MCI or dementia were investigated among 1,289 cognitively healthy elders from the National Alzheimer’s Coordinating Center (NACC) database. Results: After five years, significantly more carriers (30.6%) converted to MCI or dementia than noncarriers (17.6%), p

This special issue brings together two important reviews and seven cutting-edge empirical papers concerning the influence of alexithymia on cognitive and emotional processing. Alexithymia is a multifaceted construct that is characterised by difficulties identifying one's feelings; difficulties describing one's feelings to others; and an externally focused, utilitarian cognitive style. In this paper, we begin by considering how emotion science has evolved in its understanding of personality traits, before highlighting the potential importance of alexithymia research for the field of cognition and emotion. After summarising the historical context of alexithymia research, we consider the contributions of the featured papers to the literature of cognition and emotion. The collected works highlight that alexithymia influences several aspects of how one perceives and responds to neutral and emotional situations, by impacting upon multiple processes (attention, appraisals, memory, language and behaviour), showing the importance of drawing better connections amongst multiple processes, toward disentangling the effects of early processes on later ones. A lack of correspondence between processes, as well as amongst alexithymia facets, is another central finding of the special issue. This pattern is thought to lead to ineffective and inflexible emotion regulation and to pose significant risks for physical and mental illness.

Alexithymia is a personality trait characterized by difficulties identifying feelings (DIF), describing feelings (DDF), and externally oriented thinking (EOT). Alexithymia has been associated with poorer memory, at least for emotive materials, and recently, with executive and neural dysfunction. Aging is also accompanied by poorer memory and executive function (EF), neural dysfunction, and increasing alexithymia. Thus, the hypothesis of a general cognitive impairment in alexithymia, particularly in elders, needs investigation. Three large, independent, cross-sectional experiments (n = 296, 139 and 121, respectively) investigated memory and EF in healthy adults, ranging from young to old adulthood, with age, sex, and the three Toronto Alexithymia Scale-20 subscales (DIF, DDF, EOT) as predictors in hierarchical regressions. Across studies, alexithymia contributed to poorer memory (via EOT) and EF (via DIF), in younger and older adults. Additionally, these effects occurred in non-emotive contexts with neutral stimuli. Moreover, although memory was worse with greater age and poor EF contributed to poor memory, those who had both high EOT and poor EF had particularly poor memory. Thus, alexithymia (particularly via high DIF or high EOT) is a risk factor for age-related cognitive decline. Further research should clarify the direction and nature of these complex relationships.

Alexithymia is a multifaceted personality construct characterised by difficulties identifying one's feelings and distinguishing them from bodily sensations, difficulties describing one's feelings to others, and an externally oriented cognitive style. Over the past 25 years, a burgeoning body of research has examined how alexithymia moderates processing at the cognition-emotion interface. We review the findings in five domains: attention, appraisals, memory, language, and behaviours. The preponderance of studies linked alexithymia with deficits in emotion processing, which was apparent across all domains, except behaviours. All studies on behaviours and a proportion of studies in other domains demonstrated emotional over-responding. Analysis at the facet level revealed deficits in memory and language that are primarily associated with externally oriented thinking, while over-responding was most often linked to difficulty identifying feelings and difficulty describing feelings. The review also found evidence for contextual modulation: The pattern of deficits and over-responding was not restricted to emotional contexts but also occurred in neutral contexts, and in some circumstances, emotional over-responding in alexithymia was beneficial. Taken together, this review highlights alexithymia as a central personality dimension in the interplay between cognition and emotion.

Background: Despite advances in understanding Alzheimer’s disease (AD), prediction of AD prior to symptom onset remains severely limited, even when primary risk factors such as the apolipoprotein E (APOE) ɛ4 allele are known. Objective: Although executive dysfunction is highly prevalent and is a primary contributor to loss of independence in those with AD, few studies have examined neural differences underlying executive functioning as indicators of risk for AD prior to symptom onset, when intervention might be effective. Methods: This study examined event-related potential (ERP) differences during inhibitory control in 44 cognitively intact older adults (20 ɛ4+, 24 ɛ4-), relative to 41 young adults. All participants completed go/no-go and stop-signal tasks. Results: Overall, both older adult groups exhibited slower reaction times and longer ERP latencies compared to young adults. Older adults also had generally smaller N200 and P300 amplitudes, except at frontal electrodes and for N200 stop-signal amplitudes, which were larger in older adults. Considered with intact task accuracy, these findings suggest age-related neural compensation. Although ɛ4 did not distinguish elders during go or no-go tasks, this study uniquely showed that the more demanding stop-signal task was sensitive to ɛ4 differences, despite comparable task and neuropsychological performance with non-carriers. Specifically, ɛ4+ elders had slower frontal N200 latency and larger N200 amplitude, which was most robust at frontal sites, compared with ɛ4-. Conclusion: N200 during a stop-signal task is sensitive to AD risk, prior to any evidence of cognitive dysfunction, suggesting that stop-signal ERPs may be an important protocol addition to neuropsychological testing.

Despite advances in understanding Alzheimer’s disease (AD), prediction of AD prior to symptom onset remains severely limited, even when primary risk factors such as the apolipoprotein-E (APOE) ε4 allele are known. Objective: Although executive dysfunction is highly prevalent and is a primary contributor to loss of independence in those with AD, few studies have examined neural differences underlying executive functioning as indicators of risk for AD prior to symptom onset, when intervention might be effective. Methods: This study examined event-related potential (ERP) differences during inhibitory control in 44 cognitively intact older adults (20 ε4+, 24 ε4-), relative to 41 young adults. All participants completed go/no-go and stop-signal tasks. Results: Overall, both older adult groups exhibited slower reaction times and longer ERP latencies compared to young adults. Older adults also had generally smaller N200 and P300 amplitudes, except at frontal electrodes and for N200 stop-signal amplitudes, which were larger in older adults. Considered with intact task accuracy, these findings suggest age-related neural compensation. Although ε4 did not distinguish elders during go or no-go tasks, this study uniquely showed that the more demanding stop-signal task was sensitive to ε4 differences, despite comparable task and neuropsychological performance with non-carriers. Specifically, ε4+ elders had slower frontal N200 latency and larger N200 amplitude, which was most robust at frontal sites, compared with ε4-. Conclusion: N200 during a stop-signal task is sensitive to AD risk, prior to any evidence of cognitive dysfunction, suggesting that stop-signal ERPs may be an important protocol addition to neuropsychological testing.

This systematic review examined whether event-related potentials (ERPs) during higher cognitive processing can detect subtle, early signs of neurodegenerative disease. Original, empirical studies retrieved from PsycINFO and PubMed were reviewed if they analyzed patterns in cognitive ERPs (150ms post-stimulus) differentiating mild cognitive impairment (MCI), Alzheimer’s disease (AD), or cognitively intact elders who carry AD risk through the Apolipoprotein-E ε4 allele (ε4+) from healthy older adult controls (HC). The 100 studies meeting inclusion criteria (MCI=47; AD=47; ε4+=6) analyzed N200, P300, N400, and occasionally, later components. While there was variability across studies, patterns of reduced amplitude and delayed latency were apparent in pathological aging, consistent with AD-related brain atrophy and cognitive impairment. These effects were particularly evident in advanced disease progression (i.e., AD > MCI) and in later ERP components measured during complex tasks. Although ERP studies in intact ε4+ elders are thus far scarce, a similar pattern of delayed latency was notable, along with a contrasting pattern of increased amplitude, consistent with compensatory neural activation. This limited work suggests ERPs might be able to index early neural changes indicative of future cognitive decline in otherwise healthy elders. As ERPs are also accessible and affordable relative to other neuroimaging methods, their addition to cognitive assessment might substantively enhance early identification and characterization of neural dysfunction, allowing opportunity for earlier differential diagnosis and targeting of intervention. To evaluate this possibility there is urgent need for well-powered studies assessing late cognitive ERPs during complex tasks, particularly in healthy elders at risk for cognitive decline.

Objective:The Apolipoprotein (APOE) ε4 allele increases the risk for mild cognitive impairment (MCI) and dementia, but not all carriers develop MCI/dementia. The purpose of this exploratory study was to determine if early and subtle preclinical signs of cognitive dysfunction and medial temporal lobe atrophy are observed in cognitively intact ε4 carriers who subsequently develop MCI.Methods:Twenty-nine healthy, cognitively intact ε4 carriers (ε3/ε4 heterozygotes; ages 65–85) underwent neuropsychological testing and MRI-based measurements of medial temporal volumes over a 5-year follow-up interval; data were converted toz-scores based on a non-carrier group consisting of 17 ε3/ε3 homozygotes.Results:At follow-up, 11 ε4 carriers (38%) converted to a diagnosis of MCI. At study entry, the MCI converters had significantly lower scores on the Mini-Mental State Examination, Rey Auditory Verbal Learning Test (RAVLT) Trials 1–5, and RAVLT Immediate Recall compared to non-converters. MCI converters also had smaller MRI volumes in the left subiculum than non-converters. Follow-up logistic regressions revealed that left subiculum volumes and RAVLT Trials 1–5 scores were significant predictors of MCI conversion.Conclusions:Results from this exploratory study suggest that ε4 carriers who convert to MCI exhibit subtle cognitive and volumetric differences years prior to diagnosis.

The Deese-Roediger-McDermott (DRM) paradigm examines false memory by introducing words associated with a non-presented 'critical lure' as memoranda, which typically causes the lures to be remembered as frequently as studied words. Our prior work has shown enhanced veridical memory and reduced misinformation effects when arousal is induced after learning (i.e., during memory consolidation). These effects have not been examined in the DRM task, or with signal detection analysis, which can elucidate the mechanisms underlying memory alterations. Thus, 130 subjects studied and then immediately recalled six DRM lists, one after another, and then watched a 3-min arousing (n=61) or neutral (n=69) video. Recognition tested 70min later showed that arousal induced after learning led to better delayed discrimination of studied words from (a) critical lures, and (b) other non-presented 'weak associates.' Furthermore, arousal reduced liberal response bias (i.e., the tendency toward accepting dubious information) for studied words relative to all foils, including critical lures and 'weak associates.' Thus, arousal induced after learning effectively increased the distinction between signal and noise by enhancing access to verbatim information and reducing endorsement of dubious information. These findings provide important insights into the cognitive mechanisms by which arousal modulates early memory consolidation processes.

Background Effective interventions are needed to improve brain function in mild cognitive impairment (MCI), an early stage of Alzheimer's disease (AD). The posterior cingulate cortex (PCC)/precuneus is a hub of the default mode network (DMN) and is preferentially vulnerable to disruption of functional connectivity in MCI and AD. Objective We investigated whether 12 weeks of aerobic exercise could enhance functional connectivity of the PCC/precuneus in MCI and healthy elders. Methods Sixteen MCI and 16 healthy elders (age range = 60-88) engaged in a supervised 12-week walking exercise intervention. Functional MRI was acquired at rest; the PCC/precuneus was used as a seed for correlated brain activity maps. Results A linear mixed effects model revealed a significant interaction in the right parietal lobe: the MCI group showed increased connectivity while the healthy elders showed decreased connectivity. In addition, both groups showed increased connectivity with the left postcentral gyrus. Comparing pre to post intervention changes within each group, the MCI group showed increased connectivity in 10 regions spanning frontal, parietal, temporal and insular lobes, and the cerebellum. Healthy elders did not demonstrate any significant connectivity changes. Conclusion The observed results show increased functional connectivity of the PCC/precuneus in individuals with MCI after 12 weeks of moderate intensity walking exercise training. The protective effects of exercise training on cognition may be realized through the enhancement of neural recruitment mechanisms, which may possibly increase cognitive reserve. Whether these effects of exercise training may delay further cognitive decline in patients diagnosed with MCI remains to be demonstrated.

Intraindividual variability (IIV) in motor performance has been shown to predict future cognitive decline. The apolipoprotein E-epsilon 4 (APOE-ε4) allele is also a well-established risk factor for memory decline. Here, we present novel findings examining the influence of the APOE-ε4 allele on the performance of asymptomatic healthy elders in comparison to individuals with amnestic MCI (aMCI) on a fine motor synchronization, paced finger-tapping task (PFTT).Two Alzheimer's disease (AD) risk groups, individuals with aMCI (n = 24) and cognitively intact APOE-ε4 carriers (n = 41), and a control group consisting of cognitively intact APOE-ε4 noncarriers (n = 65) completed the Rey Auditory Verbal Learning Test and the PFTT, which requires index finger tapping in synchrony with a visual stimulus (interstimulus interval = 333 ms).Motor timing IIV, as reflected by the standard deviation of the intertap interval (ITI), was greater in the aMCI group than in the two groups of cognitively intact elders; in contrast, all three groups had statistically equivalent mean ITI. No significant IIV differences were observed between the asymptomatic APOE-ε4 carriers and noncarriers. Poorer episodic memory performance was associated with greater IIV, particularly in the aMCI group.Results suggest that increased IIV on a fine motor synchronization task is apparent in aMCI. This IIV measure was not sensitive in discriminating older asymptomatic individuals at genetic risk for AD from those without such a genetic risk. In contrast, episodic memory performance, a well-established predictor of cognitive decline in preclinical AD, was able to distinguish between the two cognitively intact groups based on genetic risk.

A cognitive challenge when imposed during a low-force isometric contraction will exacerbate sex- and age-related decreases in force steadiness, but the mechanism is not known. We determined the role of oscillations in the common synaptic input to motor units on force steadiness during a muscle contraction with a concurrent cognitive challenge. Forty-nine young adults (19–30 yr; 25 women, 24 men) and 36 old adults (60–85 yr; 19 women, 17 men) performed a cognitive challenge (counting backward by 13) during an isometric elbow flexion task at 5% of maximal voluntary contraction. Single-motor units were decomposed from high-density surface EMG recordings. For a subgroup of participants, motor units were matched during control and cognitive challenge trials, so the same motor unit was analyzed across conditions. Reduced force steadiness was associated with greater oscillations in the synaptic input to motor units during both control and cognitive challenge trials ( r = 0.45–0.47, P < 0.01). Old adults and young women showed greater oscillations in the common synaptic input to motor units and decreased force steadiness when the cognitive challenge was imposed, but young men showed no change across conditions (session × age × sex, P < 0.05). Oscillations in the common synaptic input to motor units is a potential mechanism for altered force steadiness when a cognitive challenge is imposed during low-force contractions in young women and old adults. NEW & NOTEWORTHY We found that oscillations in the common synaptic input to motor units were associated with a reduction in force steadiness when a cognitive challenge was imposed during low-force contractions of the elbow flexor muscles in young women and old men and women but not young men. Age- and sex-related muscle weakness was associated with these changes.

Objectives: White matter (WM) integrity within the mesial temporal lobe (MTL) is important for episodic memory (EM) functioning. The current study investigated the ability of diffusion tensor imaging (DTI) in MTL WM tracts to predict 3-year changes in EM performance in healthy elders at disproportionately higher genetic risk for Alzheimer’s disease (AD). Methods: Fifty-one cognitively intact elders (52% with family history (FH) of dementia and 33% possessing an Apolipoprotein E ε4 allelle) were administered the Rey Auditory Verbal Learning Test (RAVLT) at study entry and at 3-year follow-up. DTI scanning, conducted at study entry, examined fractional anisotropy and mean, radial and axial diffusion within three MTL WM tracts: uncinate fasciculus (UNC), cingulate-hippocampal (CHG), and fornix-stria terminalis (FxS). Correlations were performed between residualized change scores computed from RAVLT trials 1–5, immediate recall, and delayed recall scores and baseline DTI measures; MTL gray matter (GM) and WM volumes; demographics; and AD genetic and metabolic risk factors. Results: Higher MTL mean and axial diffusivity at baseline significantly predicted 3-year changes in EM, whereas baseline MTL GM and WM volumes, FH, and metabolic risk factors did not. Both ε4 status and DTI correlated with change in immediate recall. Conclusions: Longitudinal EM changes in cognitively intact, healthy elders can be predicted by disruption of the MTL WM microstructure. These results are derived from a sample with a disproportionately higher genetic risk for AD, suggesting that the observed WM disruption in MTL pathways may be related to early neuropathological changes associated with the preclinical stage of AD. (JINS, 2016, 22, 1005–1015)

Older adult apolipoprotein E epsilon 4 (APOE-ε4) allele carriers vary considerably in the expression of clinical symptoms of Alzheimer’s disease (AD), suggesting that lifestyle or other factors may offer protection from AD-related neurodegeneration. We recently reported that physically active APOE-ε4 allele carriers exhibit a stable cognitive trajectory and protection from hippocampal atrophy over 18 months compared to sedentary ε4 allele carriers. The aim of this study was to examine the interactions between genetic risk for AD and physical activity (PA) on white matter (WM) tract integrity, using diffusion tensor imaging (DTI) MRI, in this cohort of healthy older adults (ages of 65 to 89). Four groups were compared based on the presence or absence of an APOE-ε4 allele (High Risk; Low Risk) and self reported frequency and intensity of leisure time physical activity (PA) (High PA; Low PA). As predicted, greater levels of PA were associated with greater fractional anisotropy (FA) and lower radial diffusivity in healthy older adults who did not possess the APOE-ε4 allele. However, the effects of PA were reversed in older adults who were at increased genetic risk for AD, resulting in significant interactions between PA and genetic risk in several WM tracts. In the High Risk-Low PA participants, who had exhibited episodic memory decline over the previous 18-months, radial diffusivity was lower and fractional anisotropy was higher, compared to the High Risk-High PA participants. In WM tracts that subserve learning and memory processes, radial diffusivity (DR) was negatively correlated with episodic memory performance in physically inactive APOE-ε4 carriers, whereas DR was positively correlated with episodic memory performance in physically active APOE-ε4 carriers and the two Low Risk groups. The common model of demyelination-induced increase in radial diffusivity cannot directly explain these results. Rather, we hypothesize that PA may protect APOE-ε4 allele carriers from selective neurodegeneration of individual fiber populations at locations of crossing fibers within projection and association WM fiber tracts.

Motor performance and cognitive function both decline with aging. Older adults for example are usually less steady for a constant-force task than young adults when performing low-intensity contractions with limb muscles. Healthy older adults can also show varying degrees of cognitive decline, particularly in executive function skills. It is not known, however, whether age-related changes in steadiness of low-force tasks and cognitive function are independent of one another. In this study, we determined if executive function skills in aging are associated with the steadiness during a low-force muscle contraction performed with and without the imposition of a cognitive challenge. We recruited 60 older adults (60–85 years old, 34 women, 26 men) and 48 young adults (19–30 years old, 24 women, 24 men) to perform elbow flexor muscle contractions at 5% of maximal voluntary contraction (MVC) force in the presence and absence of a difficult mental-math task (counting backward by 13 from a four-digit number). Force steadiness was quantified as the coefficient of variation (CV) of force and executive function was estimated with the Trail-making Test part A and B. The cognitive challenge increased the CV of force (i.e., decreased force steadiness) with greater changes in older adults than young adults (5.2 vs. 1.3%, respectively, cognitive challenge × age: P < 0.001). Older adults were 35% slower in both parts A and B of the Trail-making Test (P < 0.001), and to eliminate the effects of age and education on this variable, all further analyses were performed with the age-corrected z-scores for each individual using established normative values. Hierarchical regression models indicated that decreased force steadiness during a cognitive challenge trial was in part, explained by the performance in the Trail-making Test part A and B in older (r = 0.53 and 0.50, respectively, P < 0.05), but not in young adults (P > 0.05). Thus, healthy community-dwelling older adults, who have poorer executive function skills, exhibit reduced force steadiness during tasks when also required to perform a high cognitive demand task, and are likely at risk of reduced capacity to perform daily activities that involve cognitively challenging motor tasks.

OBJECTIVE The apolipoprotein E (APOE) e4 allele is the most important genetic risk factor for late-onset Alzheimer's disease. Many e4 carriers, however, never develop Alzheimer's disease. The purpose of this study is to characterize the variability in phenotypic expression of the e4 allele, as measured by the longitudinal trajectory of cognitive test scores and MRI brain volumes, in cognitively intact elders. METHOD Healthy older adults, ages 65-85, participated in a 5-year longitudinal study that included structural MRI and cognitive testing administered at baseline and at 1.5 and 5 years postenrollment. Participants included 22 e4 noncarriers, 15 e4 carriers who experienced a decline in cognition over the 5-year interval, and 11 e4 carriers who remained cognitively stable. RESULTS No baseline cognitive or volumetric group differences were observed. Compared to noncarriers, declining e4 carriers had significantly greater rates of atrophy in left (p = .001, Cohen's d = .691) and right (p = .003, d = .622) cortical gray matter, left (p = .003, d = .625) and right (p = .020, d = .492) hippocampi, and greater expansion of the right inferior lateral ventricle (p < .001, d = .751) over 5 years. CONCLUSIONS This study illustrates the variability in phenotypic expression of the e4 allele related to neurodegeneration. Specifically, only those individuals who exhibited longitudinal declines in cognitive function experienced concomitant changes in brain volume. Future research is needed to better understand the biological and lifestyle factors that may influence the expression of the e4 allele. (PsycINFO Database Record

Cortical atrophy is a biomarker of Alzheimer’s disease (AD) that correlates with clinical symptoms. This study examined changes in cortical thickness from before to after an exercise intervention in mild cognitive impairment (MCI) and healthy elders. Thirty physically inactive older adults (14 MCI, 16 healthy controls) underwent MRI before and after participating in a 12-week moderate intensity walking intervention. Participants were between the ages of 61 and 88. Change in cardiorespiratory fitness was assessed using residualized scores of the peak rate of oxygen consumption (V̇O2peak) from pre- to post-intervention. Structural magnetic resonance images were processed using FreeSurfer v5.1.0. V̇O2peak increased an average of 8.49%, which was comparable between MCI and healthy elders. Overall, cortical thickness was stable except for a significant decrease in the right fusiform gyrus in both groups. However, improvement in cardiorespiratory fitness due to the intervention (V̇O2peak) was positively correlated with cortical thickness change in the bilateral insula, precentral gyri, precuneus, posterior cingulate, and inferior and superior frontal cortices. Moreover, MCI participants exhibited stronger positive correlations compared to healthy elders in the left insula and superior temporal gyrus. A 12-week moderate intensity walking intervention led to significantly improved fitness in both MCI and healthy elders. Improved V̇O2peak was associated with widespread increased cortical thickness, which was similar between MCI and healthy elders. Thus, regular exercise may be an especially beneficial intervention to counteract cortical atrophy in all risk groups, and may provide protection against future cognitive decline in both healthy elders and MCI. (JINS, 2015, 21, 757–767)

OBJECTIVE Alzheimer's disease (AD) research typically focuses on memory. However, executive functioning (EF) deficits are also common among AD patients; these deficits are associated with decreased functioning in activities of daily living, an important criterion in diagnosing AD. A classic test of EF ability, the Wisconsin Card Sort Test (WCST), has demonstrated sensitivity to differentiating individuals with AD from healthy controls, discriminating AD groups based on disease severity, and distinguishing AD from other types of dementia. Such sensitivity to AD raises the possibility that the WCST is also sensitive to very early, preclinical differences between those who have heightened risk for AD and those with lower risks. METHOD The current study, therefore, examined WCST performance in healthy, cognitively intact older adults with a first-degree (i.e., sibling or parent) family history (FH) of AD (n = 18) and those with no such FH of AD (n = 24). RESULTS Results revealed significant group differences for Categories Achieved, Percent Conceptual Level Responses, Total Errors, Perseverative Errors, and Non-Perseverative Errors, with the FH+ group consistently exhibiting poorer performance. Moreover, hierarchical regression analyses indicated that after accounting for age, sex, and education, FH significantly predicted all 5 of these variables. CONCLUSIONS These results speak to the potential role of EF in bolstering the current understanding of early cognitive markers of future decline. Furthering what is known about the relationship between AD and nonmemory specific domains of cognition such as executive functioning may allow for better prediction of cognitive decline and potential progression to AD.

Neuropathological changes associated with Alzheimer's disease (AD) precede symptom onset by more than a decade. Possession of an apolipoprotein E (APOE) ɛ4 allele is the strongest genetic risk factor for late onset AD. Cross-sectional studies of cognitively intact elders have noted smaller hippocampal/medial temporal volumes in ɛ4 carriers (ɛ4+) compared to ɛ4 non-carriers (ɛ4-). Few studies, however, have examined long-term, longitudinal, anatomical brain changes comparing healthy ɛ4+ and ɛ4- individuals. The current five-year study examined global and regional volumes of cortical and subcortical grey and white matter and ventricular size in 42 ɛ4+ and 30 ɛ4- individuals. Cognitively intact participants, ages 65-85 at study entry, underwent repeat anatomical MRI scans on three occasions: baseline, 1.5, and 4.75 years. Results indicated no between-group volumetric differences at baseline. Over the follow-up interval, the ɛ4+ group experienced a greater rate of volume loss in total grey matter, bilateral hippocampi, right hippocampal subfields, bilateral lingual gyri, bilateral parahippocampal gyri, and right lateral orbitofrontal cortex compared to the ɛ4- group. Greater loss in grey matter volumes in ɛ4+ participants were accompanied by greater increases in lateral, third, and fourth ventricular volumes. Rate of change in white matter volumes did not differentiate the groups. The current results indicate that longitudinal measurements of brain atrophy can serve as a sensitive biomarker for identifying neuropathological changes in persons at genetic risk for AD and potentially, for assessing the efficacy of treatments designed to slow or prevent disease progression during the preclinical stage of AD.

Background: Engagement in cognitively stimulating activities (CA) and leisure time physical activity (PA) have been associated with maintaining cognitive performance and reducing the likelihood of cognitive decline in older adults. However, neural mechanisms underlying protective effects of these lifestyle behaviors are largely unknown. In the current study, we investigated the effect of self-reported PA and CA on hippocampal volume and semantic processing activation during a fame discrimination task, as measured by functional magnetic resonance imaging (fMRI). We also examined whether possession of the apolipoprotein E (APOE) ?4 allele could moderate the effect of PA or CA on hippocampal structure or function. Methods: Seventy-eight healthy, cognitively intact older adults underwent baseline neuropsychological assessment, hippocampal volume measurement via manually-traced structural MRI, and task-activated fMRI. Results: After 18 months, 27 participants declined by one standard deviation or more on follow-up neuropsychological testing. Logistic regression analyses revealed that CA alone or in combination with baseline hippocampal structure or functional activity did not predict the probability of cognitive decline. In contrast, PA interacted with APOE 4 status such that engagement in PA reduced the risk of cognitive decline in APOE 4 carriers only. Furthermore, the benefits of PA appeared to diminish with reduced functional activity or volume in the hippocampus. Conclusions: Our findings suggest that increased leisure time PA is associated with reduced probability of cognitive decline in persons who are at high risk for AD. The beneficial effects of PA in this group may be related to enhancement of the functional and structural integrity of the hippocampus.

Extensive research efforts have been directed toward strategies for predicting risk of developing Alzheimer's disease (AD) prior to the appearance of observable symptoms. Existing approaches for early detection of AD vary in terms of their efficacy, invasiveness, and ease of implementation. Several non-invasive magnetic resonance imaging strategies have been developed for predicting decline in cognitively healthy older adults. This review will survey a number of studies, beginning with the development of a famous name discrimination task used to identify neural regions that participate in semantic memory retrieval and to test predictions of several key theories of the role of the hippocampus in memory. This task has revealed medial temporal and neocortical contributions to recent and remote memory retrieval, and it has been used to demonstrate compensatory neural recruitment in older adults, apolipoprotein E ε4 carriers, and amnestic mild cognitive impairment patients. Recently, we have also found that the famous name discrimination task provides predictive value for forecasting episodic memory decline among asymptomatic older adults. Other studies investigating the predictive value of semantic memory tasks will also be presented. We suggest several advantages associated with the use of semantic processing tasks, particularly those based on person identification, in comparison to episodic memory tasks to study AD risk. Future directions for research and potential clinical uses of semantic memory paradigms are also discussed. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.

Misinformation introduced after events have already occurred causes errors in later retrieval. Based on literature showing that arousal induced after learning enhances delayed retrieval, we investigated whether post-learning arousal can reduce the misinformation effect. 251 participants viewed four short film clips, each followed by a retention test, which for some participants included misinformation. Afterward, participants viewed another film clip that was either arousing or neutral. One week later, the arousal group recognized significantly more veridical details and endorsed significantly fewer misinformation items than the neutral group. The findings suggest that arousal induced after learning reduced source confusion, allowing participants to better retrieve accurate details and to better reject misinformation.

Person recognition can be accomplished through several modalities (face, name, voice). Lesion, neurophysiology and neuroimaging studies have been conducted in an attempt to determine the similarities and differences in the neural networks associated with person identity via different modality inputs. The current study used event-related functional-MRI in 17 healthy participants to directly compare activation in response to randomly presented famous and non-famous names and faces (25 stimuli in each of the four categories). Findings indicated distinct areas of activation that differed for faces and names in regions typically associated with pre-semantic perceptual processes. In contrast, overlapping brain regions were activated in areas associated with the retrieval of biographical knowledge and associated social affective features. Specifically, activation for famous faces was primarily right lateralized and famous names were left lateralized. However, for both stimuli, similar areas of bilateral activity were observed in the early phases of perceptual processing. Activation for fame, irrespective of stimulus modality, activated an extensive left hemisphere network, with bilateral activity observed in the hippocampi, posterior cingulate, and middle temporal gyri. Findings are discussed within the framework of recent proposals concerning the neural network of person identification.

Cognitively intact older individuals at risk for developing Alzheimer's disease frequently show increased functional magnetic resonance imaging (fMRI) brain activation presumably associated with compensatory recruitment, whereas mild cognitive impairment (MCI) patients tend not to show increased activation presumably due to reduced neural reserve. Previous studies, however, have typically used episodic memory activation tasks, placing MCI participants at a performance disadvantage relative to healthy elders. In this event-related fMRI study, we employed a low effort, high accuracy semantic memory task to determine if increased activation of memory circuits is preserved in amnestic MCI when task performance is controlled. Fifty-seven participants, aged 65-85 years, comprised three groups (n = 19 each): amnestic MCI patients; cognitively intact older participants at risk for developing Alzheimer's disease based on having at least one ApoE epsilon4 allele and a positive family history of Alzheimer's disease (At Risk); and cognitively intact participants without Alzheimer's disease risk factors (Control). fMRI was conducted on a 3T MR scanner while participants performed a famous name discrimination task. Participants also underwent neuropsychological testing outside the scanner; whole brain and hippocampal atrophy were assessed from anatomical MRI scans. The three groups did not differ on demographic variables or on fame discrimination performance (>87% correct for all groups). As expected, the amnestic MCI participants demonstrated reduced episodic memory performance. Spatial extent of activation (Fame--Unfamiliar subtraction) differentiated the three groups (Control = 0 ml, At Risk = 9.7 ml, MCI = 34.7 ml). The MCI and At Risk groups showed significantly greater per cent signal change than Control participants in 8 of 14 functionally defined regions, including the medial temporal lobe, temporoparietal junction, and posterior cingulate/precuneus. MCI participants also showed greater activation than Controls in two frontal regions. At Risk, but not MCI, participants showed increased activity in the left hippocampal complex; MCI participants, however, evidenced increased activity in this region when hippocampal atrophy was controlled. When performance is equated, MCI patients demonstrate functional compensation in brain regions subserving semantic memory systems that generally equals or exceeds that observed in cognitively intact individuals at risk for Alzheimer's disease. This hyperactivation profile in MCI is even observed in the left hippocampal complex, but only when the extent of hippocampal atrophy is taken into consideration.

The temporally graded memory impairment seen in many neurobehavioral disorders implies different neuroanatomical pathways and/or cognitive mechanisms involved in storage and retrieval of memories of different ages. A dynamic interaction between medial-temporal and neocortical brain regions has been proposed to account for memory's greater permanence with time. Despite considerable debate concerning its time-dependent role in memory retrieval, medial-temporal lobe activity has been well studied. However, the relative participation of neocortical regions in recent and remote memory retrieval has received much less attention. Using functional magnetic resonance imaging, we demonstrate robust, temporally graded signal differences in posterior cingulate, right middle frontal, right fusiform, and left middle temporal regions in healthy older adults during famous name identification from two disparate time epochs. Importantly, no neocortical regions demonstrated greater response to older than to recent stimuli. Our results suggest a possible role of these neocortical regions in temporally dating items in memory and in establishing and maintaining memory traces throughout the lifespan. Theoretical implications of these findings for the two dominant models of remote memory functioning (Consolidation Theory and Multiple Trace Theory) are discussed.

Muscle fatigability can increase when a stressful, cognitively demanding task is imposed during a low-force fatiguing contraction with the arm muscles, especially in women. Whether this occurs among older adults (> 60 years) is currently unknown. We aimed to determine if higher cognitive demands, stratified by sex, increased fatigability in older adults (> 60 years). Secondarily, we assessed if varying cognitive demand resulted in decreased steadiness and was explained by anxiety or cortisol levels. Seventeen older women (70 ± 6 years) and 13 older men (71 ± 5 years) performed a sustained, isometric, fatiguing contraction at 20% of maximal voluntary contraction until task failure during three sessions: high cognitive demand (high CD = mental subtraction by 13); low cognitive demand (low CD = mental subtraction by 1); and control (no subtraction). Fatigability was greater when high and low CD were performed during the fatiguing contraction for the women but not for the men. In women, time to failure with high CD was 16 ± 8 minutes and with low CD was 17 ± 4 minutes, both of which were shorter than time to failure in control contractions (21 ± 7 minutes; high CD mean difference: 5 minutes [95% confidence interval {CI}, 0.78–9.89], p = 0.02; low CD mean difference: 4 minutes [95% CI, 0.57–7.31], p = 0.03). However, in men, no differences were detected in time to failure with cognitive demand (control: 13 ± 5 minutes; high CD mean difference: −0.09 minutes [95% CI, −2.8 to 2.7], p = 1.00; low CD mean difference: 0.75 minutes [95% CI, −1.1 to 2.6], p = 0.85). Steadiness decreased (force fluctuations increased) more during high CD than control. Elevated anxiety, mean arterial pressure, and salivary cortisol levels in both men and women did not explain the greater fatigability during high CD. Older women but not men showed marked increases in fatigability when low or high CD was imposed during sustained static contractions with the elbow flexor muscles and contrasts with previous findings for the lower limb. Steadiness decreased in both sexes when high CD was imposed. Older women are susceptible to greater fatigability of the upper limb with heightened mental activity during sustained postural contractions, which are the foundation of many work-related tasks.

Healthy aging is associated with cognitive declines typically accompanied by increased task-related brain activity in comparison to younger counterparts. The Scaffolding Theory of Aging and Cognition (STAC) (Park and Reuter-Lorenz, 2009; Reuter-Lorenz and Park, 2014) posits that compensatory brain processes are responsible for maintaining normal cognitive performance in older adults, despite accumulation of aging-related neural damage. Cross-sectional studies indicate that cognitively intact elders at genetic risk for Alzheimer's disease (AD) demonstrate patterns of increased brain activity compared to low risk elders, suggesting that compensation represents an early response to AD-associated pathology. Whether this compensatory response persists or declines with the onset of cognitive impairment can only be addressed using a longitudinal design. The current prospective, 5-year longitudinal study examined brain activation in APOE e4 carriers (N = 24) and non-carriers (N = 21). All participants, ages 65–85 and cognitively intact at study entry, underwent task-activated fMRI, structural MRI, and neuropsychological assessments at baseline, 18, and 57 months. fMRI activation was measured in response to a semantic memory task requiring participants to discriminate famous from non-famous names. Results indicated that the trajectory of change in brain activation while performing this semantic memory task differed between APOE e4 carriers and non-carriers. The APOE e4 group exhibited greater activation than the Low Risk group at baseline, but they subsequently showed a progressive decline in activation during the follow-up periods with corresponding emergence of episodic memory loss and hippocampal atrophy. In contrast, the non-carriers demonstrated a gradual increase in activation over the 5-year period. Our results are consistent with the STAC model by demonstrating that compensation varies with the severity of underlying neural damage and can be exhausted with the onset of cognitive symptoms and increased structural brain pathology. Our fMRI results could not be attributed to changes in task performance, group differences in cerebral perfusion, or regional cortical atrophy.