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.

Moderate-to-vigorous intensity cycling exercise immediately after visual learning enhances delayed recognition memory performance.

A single bout of acute aerobic exercise has been shown to improve long-term memory, though it is unclear if exercise before learning or after learning is optimal for memory enhancement. Although some research has demonstrated that exercise before learning is ideal, investigations have consistently shown that acute arousal post-learning is a powerful memory enhancer. Therefore, the purpose of this investigation was to compare the effects of self-perceived hard cycling before or after learning on recognition memory for emotional and neutral images, and examine the relationship between central noradrenergic activity and memory performance. Seventy-two males and females (18-35 years of age) participated in this between-subjects study. Participants were randomly assigned to one of the following groups: exercise before learning, exercise after learning, and control. Participants in the exercise groups engaged in 20 min of cycling at a rating of perceived exertion (RPE) of 15 ("hard") on the Borg RPE scale before or after viewing a series of 90 pleasant, unpleasant, and neutral images (30 each). Participants in the control group engaged in no exercise before or after image viewing. At several time points throughout the experiment, saliva was collected to measure salivary alpha amylase (sAA), a marker of central noradrenergic activity. One-week later, recognition memory was assessed where participants viewed 180 images (90 new) and had to identify which images were previously viewed. Participants in the exercise after learning group had significantly higher recognition memory compared to the control group, but this was not seen with exercise before learning. sAA was not correlated with memory in any group, though it did increase during exercise. These results demonstrate that acute self-perceived hard cycling post-learning, but not pre-learning, improves recognition memory, though this was unrelated to the exercise-induced increase in central noradrenergic activity as measured in saliva.

Cerebellar EEG source localization reveals age-related compensatory activity moderated by genetic risk for Alzheimer's disease.

The apolipoprotein-E (APOE) ε4 allele is the greatest genetic risk factor for late-onset Alzheimer's disease (AD), but alone it is not sufficiently predictive. Because neuropathological changes associated with AD begin decades before cognitive symptoms, neuroimaging of healthy, cognitively intact ε4 carriers (ε4+) may enable early characterization of patterns associated with risk for future decline. Research in the cerebral cortex highlights a period of compensatory recruitment in elders and ε4+, which serves to maintain cognitive functioning. Yet, AD-related changes may occur even earlier in the cerebellum. Advances in electroencephalography (EEG) source localization now allow effective modeling of cerebellar activity. Importantly, healthy aging and AD are associated with declines in both cerebellar functions and executive functioning (EF). However, it is not known whether cerebellar activity can detect pre-symptomatic AD risk. Thus, the current study analyzed cerebellar EEG source localization during an EF-dependent stop-signal task (i.e., inhibitory control) in healthy, intact older adults (Mage = 80 years; 20 ε4+, 25 ε4-). Task performance was comparable between groups. Older age predicted greater activity in left crus II and lobule VIIb during the P300 window (i.e., performance evaluation), consistent with age-related compensation. Age*ε4 moderations specifically showed that compensatory patterns were evident only in ε4-, suggesting that cerebellar compensatory resources may already be depleted in healthy ε4+ elders. Thus, the posterolateral cerebellum is sensitive to AD-related neural deficits in healthy elders. Characterization of these patterns may be essential for the earliest possible detection of AD risk, which would enable critical early intervention prior to symptom onset.

Large-Scale Network Connectivity and Cognitive Function Changes After Exercise Training in Older Adults with Intact Cognition and Mild Cognitive Impairment.

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.

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.

Subjective Well-Being and Bilateral Anterior Insula Functional Connectivity After Exercise Intervention in Older Adults With Mild Cognitive Impairment.

While it is well known that exercise training is associated with improvement in subjective well-being among older adults, it is unclear if individuals with cognitive impairment experience the same effects elicited by exercise on subjective well-being. We further explored whether the bilateral anterior insula network may be an underlying neural mechanism for the exercise training-related improvements in subjective well-being. We investigated the effects of exercise training on subjective well-being in older adults (78.4 ± 7.1 years) with mild cognitive impairment (MCI; n = 14) and a cognitively normal (CN; n = 14) control group. We specifically assessed the relationship between changes in subjective well-being and changes in functional connectivity (FC) with the bilateral anterior insula from before to after exercise training. Cardiorespiratory fitness, subjective well-being, and resting-state fMRI were measured before and after a 12-week moderate-intensity walking intervention. A seed-based correlation analysis was conducted using the bilateral anterior insula as a priori seed regions of interest. The associations between bilateral anterior insula FC with other brain regions and subjective well-being were computed before and after exercise training, respectively, and the statistical difference between the correlations (before vs after exercise training) was evaluated. There was a significant Group (MCI vs CN) × Time (before vs after exercise training) interaction for subjective well-being, such that while those with MCI demonstrated significantly increased subjective well-being after exercise training, no changes in subjective well-being were observed in CN. Participants with MCI also showed an exercise training-related increase in the bilateral anterior insula FC. While there was no significant correlation between subjective well-being and bilateral anterior insula FC before exercise training, a positive association between subjective well-being and bilateral anterior insula FC was found in the MCI group after exercise training. Our findings indicate that 12 weeks of exercise training may enhance subjective well-being in older adults diagnosed with MCI and, further, suggest that increased bilateral anterior insula FC with other cortical regions may reflect neural network plasticity associated with exercise training-related improvements in subjective well-being.

Hippocampal Functional Connectivity and Memory Performance After Exercise Intervention in Older Adults with Mild Cognitive Impairment.

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.

Exercise Training-Related Changes in Cortical Gray Matter Diffusivity and Cognitive Function in Mild Cognitive Impairment and Healthy Older Adults.

Individuals with Mild Cognitive Impairment (MCI) are at an elevated risk of dementia and exhibit deficits in cognition and cortical gray matter (GM) volume, thickness, and microstructure. Meanwhile, exercise training appears to preserve brain function and macrostructure may help delay or prevent the onset of dementia in individuals with MCI. Yet, our understanding of the neurophysiological effects of exercise training in individuals with MCI remains limited. Recent work suggests that the measures of gray matter microstructure using diffusion imaging may be sensitive to early cognitive and neurophysiological changes in the aging brain. Therefore, this study is aimed to determine the effects of exercise training in cognition and cortical gray matter microstructure in individuals with MCI vs. cognitively healthy older adults. Fifteen MCI participants and 17 cognitively intact controls (HC) volunteered for a 12-week supervised walking intervention. Following the intervention, MCI and HC saw improvements in cardiorespiratory fitness, performance on Trial 1 of the Rey Auditory Verbal Learning Test (RAVLT), a measure of verbal memory, and the Controlled Oral Word Association Test (COWAT), a measure of verbal fluency. After controlling for age, a voxel-wise analysis of cortical gray matter diffusivity showed individuals with MCI exhibited greater increases in mean diffusivity (MD) in the left insular cortex than HC. This increase in MD was positively associated with improvements in COWAT performance. Additionally, after controlling for age, the voxel-wise analysis indicated a main effect of Time with both groups experiencing an increase in left insular and left and right cerebellar MD. Increases in left insular diffusivity were similarly found to be positively associated with improvements in COWAT performance in both groups, while increases in cerebellar MD were related to gains in episodic memory performance. These findings suggest that exercise training may be related to improvements in neural circuits that govern verbal fluency performance in older adults through the microstructural remodeling of cortical gray matter. Furthermore, changes in left insular cortex microstructure may be particularly relevant to improvements in verbal fluency among individuals diagnosed with MCI.

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.

Event-Related Potentials, Inhibition, and Risk for Alzheimer's Disease Among Cognitively Intact Elders.

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.

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.

Five-Year Change in Body Mass Index Predicts Conversion to Mild Cognitive Impairment or Dementia Only in APOE ɛ4 Allele Carriers.

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 < 0.001, OR = 2.06. Neither bBMI (OR = 0.99, 95%CI = 0.96-1.02) nor the bBMI by APOE interaction (OR = 1.02, 95%CI = 0.96-1.08) predicted conversion. Although ΔBMI also did not significantly predict conversion (OR = 0.90, 95%CI = 0.78-1.04), the interaction between ΔBMI and carrier status was significant (OR = 0.72, 95%CI = 0.53-0.98). For carriers only, each one-unit decline in BMI over five years was associated with a 27%increase in the odds of conversion (OR = 0.73, 95%CI = 0.57-0.94). CONCLUSION: A decline in BMI over five years, but not bBMI, was strongly associated with conversion to MCI or dementia only for APOE ɛ4 carriers. Interventions and behaviors aimed at maintaining body mass may be important for long term cognitive health in older adults at genetic risk for AD.

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.

Temporal Dynamics of Event-Related Potentials during Inhibitory Control Characterize Age-Related Neural Compensation.

Aging is accompanied by frontal lobe and non-dominant hemisphere recruitment that supports executive functioning, such as inhibitory control, which is crucial to all cognitive functions. However, the spatio-temporal sequence of processing underlying successful inhibition and how it changes with age is understudied. Thus, we capitalized on the temporal precision of event-related potentials (ERPs) to assess the functional lateralization of N200 (conflict monitoring) and P300 (inhibitory performance evaluation) in young and healthy older adults during comparably performed successful stop-signal inhibition. We additionally used temporal principal components analysis (PCA) to further interrogate the continuous spatio-temporal dynamics underlying N200 and P300 activation for each group. Young adults demonstrated left hemisphere-dominant N200, while older adults demonstrated overall larger amplitudes and right hemisphere dominance. N200 activation was explained by a single PCA factor in both age groups, but with a more anterior scalp distribution in older adults. The P300 amplitudes were larger in the right hemisphere in young, but bilateral in old, with old larger than young in the left hemisphere. P300 was also explained by a single factor in young adults but by two factors in older adults, including distinct parieto-occipital and anterior activation. These findings highlight the differential functional asymmetries of conflict monitoring (N200) and inhibitory evaluation and adaptation (P300) processes and further illuminate unique age-related spatio-temporal recruitment patterns. Older adults demonstrated lateralized recruitment during conflict processing and bilateral recruitment during evaluation and adaptation, with anterior recruitment common to both processes. These fine-grained analyses are critically important for more precise understanding of age-related compensatory activation.

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.

A systematic review of cognitive event-related potentials in mild cognitive impairment and Alzheimer's disease.

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 (≥150 ms 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.

A Review of Minority Stress as a Risk Factor for Cognitive Decline in Lesbian, Gay, Bisexual, and Transgender (LGBT) Elders.

Lesbian, gay, bisexual, and transgender (LGBT) older adults comprise a unique and growing subset of the aging population. The historical context in which they came of age was imbued with victimization and discrimination. These experiences are subjectively stressful and collectively known as minority stress. Older LGBT adults continue to face stressors related to their gender and sexual identities in their daily lives. Importantly, chronic minority stress (CMS), like other forms of chronic stress, is harmful to health and well-being. CMS contributes to LGBT health disparities, including cardiovascular disease and depression, conditions that in turn increase risk for premature cognitive decline. Furthermore, long-term exposure to stress hormones is associated with accelerated brain aging. Yet, the cognitive functioning of LGBT elders and the influence of CMS on their cognition is all but unexplored. In this review, we examine the influences of CMS in LGBT elders and connect those influences to existing research on stress and cognitive aging. We propose a testable model describing how CMS in LGBT elders heightens risk for premature cognitive aging and how ameliorating factors may help protect from CMS risk. Research is desperately needed to calibrate this model toward improving LGBT quality of life and mental health practices.

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.