When intercepting moving targets, mid-movement error corrections reflect distinct responses to visual and haptic perturbations.

We examined a key aspect of sensorimotor skill: the capability to correct performance errors that arise mid-movement. Participants grasped the handle of a robot that imposed a nominal viscous resistance to hand movement. They watched a target move pseudo-randomly just above the horizontal plane of hand motion and initiated quick interception movements when cued. On some trials, the robot's viscosity or the target's speed changed without warning coincident with the GO cue. We fit a sum-of-Gaussians model to mechanical power measured at the handle to determine the number, magnitude, and relative timing of submovements occurring in each interception attempt. When a single submovement successfully intercepted the target, capture times averaged 410 ms. Sometimes, two or more submovements were required. Initial error corrections typically occurred before feedback could indicate the target had been captured or missed. Error corrections occurred sooner after movement onset in response to mechanical viscosity increases (at 154 ms) than to unprovoked errors on control trials (215 ms). Corrections occurred later (272 ms) in response to viscosity decreases. The latency of corrections for target speed changes did not differ from those in control trials. Remarkably, these early error corrections accommodated the altered testing conditions; speed/viscosity increases elicited more vigorous corrections than in control trials with unprovoked errors; speed/viscosity decreases elicited less vigorous corrections. These results suggest that the brain monitors and predicts the outcome of evolving movements, rapidly infers causes of mid-movement errors, and plans and executes corrections-all within 300 ms of movement onset.

Association Between Greater Cerebellar Network Connectivity and Improved Phonemic Fluency Performance After Exercise Training in Older Adults.

Little is known about the effects of exercise training (ET) on lexical characteristics during fluency task and its association with cerebellum functional connectivity. The purposes of this study were (1) to investigate whether ET alters response patterns during phonemic and semantic fluency tasks and (2) to assess the association between ET-related changes in cerebellum functional connectivity (FC) and lexical characteristics during fluency tasks. Thirty-five older adults (78.0 ± 7.1 years; 17 mild cognitive impairment (MCI) and 18 healthy cognition (HC)) underwent a 12-week treadmill ET. Before and after ET, cardiorespiratory fitness tests, phonemic and semantic fluency tests, and resting-state fMRI scans were administered. We utilized a seed-based correlation analysis to measure cerebellum FC and linear regression to assess the association of residualized ET-induced Δcerebellum FC with Δtask performance. Improved mean switches and frequency during the phonemic fluency task were observed following ET in all participants. There were significant associations between ET-induced increases in cerebellum FC and greater phonemic fluency task log frequency, increases in mean switches, and a reduction in the number of syllables in HC. Lastly, there was a significant interaction between group and cerebellar connectivity on phonemic fluency mean log frequency and number of syllables. A 12-week walking ET is related to enhanced phonemic fluency lexical characteristics in older adults with MCI and HC. The association between ET-induced increases in cerebellum FC and enhanced response patterns after ET suggests that the cerebellum may play an important role in ET-related improvement in phonemic fluency performance in cognitively healthy older adults.

Having no words for feelings: alexithymia as a fundamental personality dimension at the interface of cognition and emotion.

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.

Cognitive-emotional processing in alexithymia: an integrative review.

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.

The role of alexithymia in memory and executive functioning across the lifespan.

Alexithymia is a personality trait characterised 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 functioning (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.

Episodic Memory and Hippocampal Volume Predict 5-Year Mild Cognitive Impairment Conversion in Healthy Apolipoprotein ε4 Carriers.

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 to z-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.

Post-learning arousal enhances veridical memory and reduces false memory in the Deese-Roediger-McDermott paradigm.

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.

Interactive effects of physical activity and APOE-ε4 on white matter tract diffusivity in healthy elders.

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 18months 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.

Diffusion Tensor Imaging Predictors of Episodic Memory Decline in Healthy Elders at Genetic Risk for Alzheimer's Disease.

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).

Genetic risk for Alzheimer's disease alters the five-year trajectory of semantic memory activation in cognitively intact elders.

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 ε4 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 ε4 carriers and non-carriers. The APOE ε4 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.

Improved Cardiorespiratory Fitness Is Associated with Increased Cortical Thickness in Mild Cognitive Impairment.

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.

Age and sex differences in steadiness of elbow flexor muscles with imposed cognitive demand.

PURPOSE: These studies determined (1) age- and sex-related differences in steadiness of isometric contractions when high cognitive demand was imposed across a range of forces with the elbow flexor muscles (study 1) and; (2) sex differences in steadiness among older adults when low cognitive demand was imposed (study 2). METHODS: 36 young adults (18-25 years; 18 women) and 30 older adults (60-82 years; 17 women) performed isometric contractions at 5, 30 and 40 % of maximum voluntary contraction (MVC). Study 1 involved a high-cognitive demand session (serial subtractions by 13 during the contraction) and a control session (no mental math). Study 2 (older adults only) involved a low-cognitive demand session (subtracting by 1s). RESULTS: Older individuals exhibited greater increases in force fluctuations (coefficient of variation of force, CV) with high cognitive demand than young adults, with the largest age difference at 5 % MVC (P = 0.01). Older adults had greater agonist EMG activity with high-cognitive demand and women had greater coactivation than men (P < 0.05). In study 2, CV of force increased with low cognitive demand for the older women but not for the older men (P = 0.03). CONCLUSION: Older adults had reduced steadiness and increased muscle activation when high cognitive demand was imposed while low cognitive demand induced increased force fluctuations in older women but not older men. These findings have implications for daily and work-related tasks that involve cognitive demand performed simultaneously during submaximal isometric contractions in an aging workforce.

Sex Differences in Arm Muscle Fatigability With Cognitive Demand in Older Adults.

BACKGROUND: 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. QUESTIONS/PURPOSES: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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. CLINICAL RELEVANCE: 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.

Alexithymia impairs the cognitive control of negative material while facilitating the recall of neutral material in both younger and older adults.

We investigated the moderating impact of the personality construct alexithymia on the ability of younger and older adults to control the recall of negative and neutral material. We conducted two experiments using the directed forgetting paradigm with younger and older adults. Participants studied negative (Experiment 1) or neutral (Experiment 2) words. Participants were instructed to forget the first half and remember the second half of an entire list of words. Overall, we found that alexithymia impairs the ability of both younger and older adults to cognitively control negative material (through both recall and inhibition). The "externally oriented thinking" factor of alexithymia appears to play a particularly pertinent role in terms of inhibiting negative material. Furthermore, older adults recalled fewer sought after negative items, but this was not evident in terms of inhibition. In contrast, only age (older adults) negatively impacted the recall of sought after neutral items. Interestingly, alexithymia had the opposite effect: the "difficulty in identifying emotions" factor of alexithymia was associated with an increased recall of neutral items. We discuss these results in terms of alexithymia and its impact on cognitive control.

Muscle tension induced after learning enhances long-term narrative and visual memory in healthy older adults.

Arousing events are better remembered than mundane events. Indeed, manipulation of arousal, such as by muscle tension, can influence memory even when it occurs shortly after learning. Indeed, our founding study showed this approach can raise delayed memory performance in older adults to a level comparable to that of unaided young adults. Yet, systematic studies, especially those investigating different modalities or types of memory, have not been done. This study investigated the effects of a brief bout of isometric exercise via handgrip on narrative and visuospatial episodic memory in healthy elders. Forty-seven participants completed the Logical Memory subtest of the Wechsler Memory Scales III (LM) and the Benton Visual Retention Test (BVRT), followed alternately by no treatment and by moderately squeezing a sand-filled latex ball for 1-min (counterbalanced order and test forms). Isometric exercise significantly increased both positive and negative affect ratings. Retention was tested 2 weeks later. Delayed recall and recognition of LM was enhanced by arousal relative to control, as was recognition of the BVRT. The results extend past findings that muscle tension induced after learning modulates memory consolidation, extending findings in elders to suggest that a simple form of isometric exercise can have practical effects, such as aiding memory for stories and images.

Brain areas associated with force steadiness and intensity during isometric ankle dorsiflexion in men and women.

Although maintenance of steady contractions is required for many daily tasks, there is little understanding of brain areas that modulate lower limb force accuracy. Functional magnetic resonance imaging was used to determine brain areas associated with steadiness and force during static (isometric) lower limb target-matching contractions at low and high intensities. Fourteen young adults (6 men and 8 women; 27.1 ± 9.1 years) performed three sets of 16-s isometric contractions with the ankle dorsiflexor muscles at 10, 30, 50, and 70 % of maximal voluntary contraction (MVC). Percent signal changes (PSCs, %) of the blood oxygenation level-dependent response were extracted for each contraction using region of interest analysis. Mean PSC increased with contraction intensity in the contralateral primary motor area (M1), supplementary motor area, putamen, pallidum cingulate cortex, and ipsilateral cerebellum (p < 0.05). The amplitude of force fluctuations (standard deviation, SD) increased from 10 to 70 % MVC but relative to the mean force (coefficient of variation, CV %) was greatest at 10 % MVC. The CV of force was associated with PSC in the ipsilateral parietal lobule (r = -0.28), putamen (r = -0.29), insula (r = -0.33), and contralateral superior frontal gyrus (r = -0.33, p < 0.05). There were minimal sex differences in brain activation across the isometric motor tasks indicating men and women were similarly motivated and able to activate cortical motor centers during static tasks. Control of steady lower limb contractions involves cortical and subcortical motor areas in both men and women and provides insight into key areas for potential cortical plasticity with impaired or enhanced leg function.

Genetic Risk for Alzheimer's Disease Alters Perceived Executive Dysfunction in Cognitively Healthy Middle-Aged and Older Adults.

Background: Subjective cognitive complaints (SCC) may be an early indicator of future cognitive decline. However, findings comparing SCC and objective cognitive performance have varied, particularly in the memory domain. Even less well established is the relationship between subjective and objective complaints in non-amnestic domains, such as in executive functioning, despite evidence indicating very early changes in these domains. Moreover, particularly early changes in both amnestic and non-amnestic domains are apparent in those carrying the Apolipoprotein-E ɛ4 allele, a primary genetic risk for Alzheimer's disease (AD). Objective: This study investigated the role of the ɛ4 allele in the consistency between subjective and objective executive functioning in 54 healthy, cognitively intact, middle-aged and older adults. Methods: Participants (Mage = 64.07, SD = 9.27, range = 48-84; ɛ4+ = 18) completed the Frontal Systems Behavior Scale (FrSBe) Executive Dysfunction Scale (EXECDYS) to measure subjective executive functioning (SEF) and multiple executive functioning tasks, which were condensed into a single factor. Results: After accounting for age, depression, and anxiety, objective executive functioning performance significantly predicted SEF. Importantly, ɛ4 moderated this effect. Specifically, those carrying the ɛ4 allele had significantly less accurate self-awareness of their executive functioning compared to ɛ4 non-carriers. Conclusions: Utilizing an approach that integrates self-evaluation of executive functioning with objective neurocognitive assessment may help identify the earliest signs of impending cognitive decline, particularly in those with genetic risk for AD. Such an approach could sensitively determine those most prone to future cognitive decline prior to symptom onset, when interventions could be most effective.

Exercise and Protection from Age-Related Cognitive Decline.

In this chapter, we review the cross-sectional evidence in healthy human subjects for physical activity and cardiorespiratory fitness to offer neuroprotection and moderate cognitive decline in older age. The role of exercise training on cognition in healthy older adults and those diagnosed with mild cognitive impairment (MCI) is also discussed, including the evidence from neuroimaging studies that document changes to brain structure and function after a period of exercise training and improved fitness. Finally, in reference to animal models, the potential neurophysiological mechanisms for physical activity and exercise to impact human brain health are highlighted.

Functional magnetic resonance imaging of semantic memory as a presymptomatic biomarker of Alzheimer's disease risk.

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.

Comparison of semantic and episodic memory BOLD fMRI activation in predicting cognitive decline in older adults.

Previous studies suggest that task-activated functional magnetic resonance imaging (fMRI) can predict future cognitive decline among healthy older adults. The present fMRI study examined the relative sensitivity of semantic memory (SM) versus episodic memory (EM) activation tasks for predicting cognitive decline. Seventy-eight cognitively intact elders underwent neuropsychological testing at entry and after an 18-month interval, with participants classified as cognitively "Stable" or "Declining" based on ≥ 1.0 SD decline in performance. Baseline fMRI scanning involved SM (famous name discrimination) and EM (name recognition) tasks. SM and EM fMRI activation, along with Apolipoprotein E (APOE) ε4 status, served as predictors of cognitive outcome using a logistic regression analysis. Twenty-seven (34.6%) participants were classified as Declining and 51 (65.4%) as Stable. APOE ε4 status alone significantly predicted cognitive decline (R(2) = .106; C index = .642). Addition of SM activation significantly improved prediction accuracy (R(2) = .285; C index = .787), whereas the addition of EM did not (R(2) = .212; C index = .711). In combination with APOE status, SM task activation predicts future cognitive decline better than EM activation. These results have implications for use of fMRI in prevention clinical trials involving the identification of persons at-risk for age-associated memory loss and Alzheimer's disease.