Late-life physical activity relates to brain tissue synaptic integrity markers in older adults.

INTRODUCTION: Physical activity (PA) is widely recommended for age-related brain health, yet its neurobiology is not well understood. Animal models indicate PA is synaptogenic. We examined the relationship between PA and synaptic integrity markers in older adults. METHODS: Four hundred four decedents from the Rush Memory and Aging Project completed annual actigraphy monitoring (Mean visits = 3.5±2.4) and post mortem evaluation. Brain tissue was analyzed for presynaptic proteins (synaptophysin, synaptotagmin-1, vesicle-associated membrane proteins, syntaxin, complexin-I, and complexin-II), and neuropathology. Models examined relationships between late-life PA (averaged across visits), and timing-specific PA (time to autopsy) with synaptic proteins. RESULTS: Greater late-life PA associated with higher presynaptic protein levels (0.14 < ß < 0.20), except complexin-II (ß = 0.08). Relationships were independent of pathology but timing specific; participants who completed actigraphy within 2 years of brain tissue measurements showed largest PA-to-synaptic protein associations (0.32 < ß < 0.38). Relationships between PA and presynaptic proteins were comparable across brain regions sampled. DISCUSSION: PA associates with synaptic integrity in a regionally global, but time-linked nature in older adults.

Relationship between objectively measured physical activity on neuropathology and cognitive outcomes in older adults: Resistance versus resilience?

INTRODUCTION: Physical activity (PA) is associated with better cognitive and brain health. However, it remains unclear whether PA relates to accumulation of disease pathology ("resistance") or indirectly moderates adverse effects of pathology on cognition ("cognitive resilience"). METHODS: Five hundred thirteen Rush Memory and Aging Project (MAP) decedents completed longitudinal actigraphy monitoring, cognitive testing, and neuropathological examination. Cross-sectional models tested the relationship between average PA and pathology, and the moderating effect of baseline PA on the association between pathology and cognition. Longitudinal models examined whether changes in PA moderated associations between pathology and cognition. RESULTS: PA was negatively associated with Lewy body disease (LBD), but positively associated with Alzheimer's disease (AD) burdens. Baseline PA attenuated the association between cerebrovascular pathology and cognition, whereas longitudinal change in PA attenuated associations between AD, cerebral amyloid angiopathy, TAR DNA-binding protein 43, and atherosclerosis on cognitive decline. DISCUSSION: Whereas PA relates to "cognitive resilience" against cerebrovascular disease, AD, and other neuropathologies, "resistance" effects were limited.

Autobiographical recall of a stressful negative event in veterans with PTSD.

Posttraumatic stress disorder (PTSD) is characterised by alterations in autobiographical memory for traumatic and non-traumatic events. Studies that focus on event construction - the ability to search for and identify a specific event - have documented overgeneral memory in PTSD. However, the quality of autobiographical memory also depends on the ability to elaborate on an event once constructed by providing additional details. In a prior study, individuals with PTSD generated as many episodic (event-specific) details as trauma-exposed controls when demands on event construction were minimized, albeit the PTSD group generated more non-episodic details. The current study sought to further characterize PTSD-related alterations in event elaboration by asking participants to describe a stressful negative event specified by the experimenter, thus minimizing event construction demands. Narratives were scored for episodic and non-episodic details and relations with measures of executive function and self-reported avoidance were examined. Compared to controls, the PTSD group generated narratives with equivalent episodic detail but greater non-episodic detail, including semantic information and repeated or extended events. Non-episodic detail generation was associated with greater avoidance but not executive functions. Elaborated non-trauma memories may be perceived as overgeneral in PTSD due to greater generation of non-episodic details, rather than diminished episodic detail.

APOE moderates the effect of hippocampal blood flow on memory pattern separation in clinically normal older adults.

Pattern separation, the ability to differentiate new information from previously experienced similar information, is highly sensitive to hippocampal structure and function and declines with age. Functional MRI studies have demonstrated hippocampal hyperactivation in older adults compared to young, with greater task-related activation associated with worse pattern separation performance. The current study was designed to determine whether pattern separation was sensitive to differences in task-free hippocampal cerebral blood flow (CBF) in 130 functionally intact older adults. Given prior evidence that apolipoprotein E e4 (APOE e4) status moderates the relationship between CBF and episodic memory, we predicted a stronger negative relationship between hippocampal CBF and pattern separation in APOE e4 carriers. An interaction between APOE group and right hippocampal CBF was present, such that greater right hippocampal CBF was related to better lure discrimination in noncarriers, whereas the effect reversed directionality in e4 carriers. These findings suggest that neurovascular changes in the medial temporal lobe may underlie memory deficits in cognitively normal older adults who are APOE e4 carriers.

The relationship between episodic detail generation and anterotemporal, posteromedial, and hippocampal white matter tracts.

Episodic details populate autobiographical memories with vivid representations of people, objects, and event happenings, and they link events to a specific time and place. Episodic detail generation is believed to be a function of medial temporal lobe (MTL)-cortical interaction, but much remains unclear about how this retrieval process unfolds. In the present study, we combined an autobiographical interview and diffusion magnetic resonance imaging to investigate the relationships of two types of episodic detail, namely details about entities of an event (people and objects) or "event elements" and details about spatiotemporal context, to the integrity of anterotemporal (uncinate fasciculus; UF) and posteromedial (cingulum bundle; CB) cortical pathways. We also measured the relationships of these detail types to the fornix, and the relationship between non-episodic details and these tracts. We found that only episodic detail generation was significantly related to cortical and hippocampal pathways. Notably, the UF was more strongly related to event element details than it was to spatiotemporal context details. In contrast, CB was significantly and similarly related to the generation of event element and spatiotemporal context details (when not controlling for age and global diffusion). The fornix was also significantly related to both types of episodic detail, although the relationship to spatiotemporal context was particularly robust. These findings support the idea that anterotemporal cortical regions are related to the retrieval of episodic details about the entities that are incorporated into autobiographical events. Our findings also align with the notion that posteromedial and hippocampal-cortical involvement support the retrieval of episodic details.

Working memory predicts subsequent episodic memory decline during healthy cognitive aging: evidence from a cross-lagged panel design.

Aging adults experience declines in working memory and episodic memory, however, it is unclear how these declines operate over time. Decreased working memory may be associated with early changes in episodic memory, by reducing older adults' ability to meaningfully integrate new information into pre-existing schemas and recall information without the assistance of cues. Given the increased prevalence of Alzheimer's disease, and concerns based on subjective memory changes, it is important to understand how these processes interact over time. To assess the relationship between working memory and episodic memory during healthy cognitive aging, we performed neuropsychological assessments at multiple time points in a sample of 310 community-dwelling older adults. Using a cross-lagged panel design, we demonstrated that the lagged associations between working memory and later episodic free recall were 50% larger than the lagged associations between episodic recall and later working memory, suggesting working memory may be a useful metric of future episodic memory decline.

Visual integration of objects and scenes increases recollection-based responding despite differential MTL recruitment in young and older adults.

Unitization, the process of encoding previously independent units as one coherent representation, improves associative memory in both young and older adults, or in some cases, differentially benefits older adults. Unitization of verbal associative pairs may reduce reliance on the hippocampus (HC) for successful encoding and recognition by shifting to familiarity-based processing mediated by perirhinal cortex (PRC). However, this shift was not observed in a recent study of visual associative memory, with equivalent activation in HC and PRC during encoding of visually integrated (unitized) and nonintegrated object and scene pairs. Furthermore, behavioral findings from this study suggested an increase in recollection rather than familiarity during recognition of visually integrated pairs. The present study extends our previous work by focusing on the influence of visual integration on fMRI activation during associative recognition, rather than encoding and these patterns between young and older adults. In contrast to our findings from encoding, visual integration reduced HC and PRC activation during retrieval of object and scene associative pairs across both age groups. However, visual integration increased the correlation between bilateral HC and left parahippocampal (PHC) activation and behavioral performance among older adults, consistent with an increased reliance on recollection. In contrast, visual integration reduced the correlation between HC activation and behavioral performance in young adults, more consistent with findings from the verbal unitization literature. Taken together, these results suggest that associative memory for visually integrated pairs may involve differential recruitment of medial temporal regions in young and older adults.

Visual integration enhances associative memory equally for young and older adults without reducing hippocampal encoding activation.

The ability to remember associations between previously unrelated pieces of information is often impaired in older adults (Naveh-Benjamin, 2000). Unitization, the process of creating a perceptually or semantically integrated representation that includes both items in an associative pair, attenuates age-related associative deficits (Bastin et al., 2013; Ahmad et al., 2015; Zheng et al., 2015). Compared to non-unitized pairs, unitized pairs may rely less on hippocampally-mediated binding associated with recollection, and more on familiarity-based processes mediated by perirhinal cortex (PRC) and parahippocampal cortex (PHC). While unitization of verbal materials improves associative memory in older adults, less is known about the impact of visual integration. The present study determined whether visual integration improves associative memory in older adults by minimizing the need for hippocampal (HC) recruitment and shifting encoding to non-hippocampal medial temporal structures, such as the PRC and PHC. Young and older adults were presented with a series of objects paired with naturalistic scenes while undergoing fMRI scanning, and were later given an associative memory test. Visual integration was varied by presenting the object either next to the scene (Separated condition) or visually integrated within the scene (Combined condition). Visual integration improved associative memory among young and older adults to a similar degree by increasing the hit rate for intact pairs, but without increasing false alarms for recombined pairs, suggesting enhanced recollection rather than increased reliance on familiarity. Also contrary to expectations, visual integration resulted in increased hippocampal activation in both age groups, along with increases in PRC and PHC activation. Activation in all three MTL regions predicted discrimination performance during the Separated condition in young adults, while only a marginal relationship between PRC activation and performance was observed during the Combined condition. Older adults showed less overall activation in MTL regions compared to young adults, and associative memory performance was most strongly predicted by prefrontal, rather than MTL, activation. We suggest that visual integration benefits both young and older adults similarly, and provides a special case of unitization that may be mediated by recollective, rather than familiarity-based encoding processes.

Social participation predicts cognitive functioning in aging adults over time: comparisons with physical health, depression, and physical activity.

OBJECTIVES: Several risk and protective factors are associated with changes in cognitive functioning in aging adults - including physical health, depression, physical activity, and social activities - though the findings for participation in social activities are mixed. This study investigated the longitudinal association between social participation and two domains of cognitive functioning, memory and executive function. A primary goal of our analyses was to determine whether social participation predicted cognitive functioning over-and-above physical health, depression, and physical activity in a sample with adequate power to detect unique effects. METHOD: The sample included aging adults (N = 19,832) who participated in a large, multi-national study and provided data across six years; split into two random subsamples. Unique associations between the predictors of interest and cognitive functioning over time and within occasion were assessed in a latent curve growth model. RESULTS: Social participation predicted both domains of cognitive functioning at each occasion, and the relative magnitude of this effect was comparable to physical health, depression, and physical activity level. In addition, social participation at the first time point predicted change in cognitive functioning over time. The substantive results in the initial sample were replicated in the second independent subsample. CONCLUSION: Overall, the magnitude of the association of social participation is comparable to other well-established predictors of cognitive functioning, providing evidence that social participation plays an important role in cognitive functioning and successful aging.

Body Mass and Physical Activity Uniquely Predict Change in Cognition for Aging Adults.

BACKGROUND: Physical activity and body mass predict cognition in the elderly. However, mixed evidence suggests that obesity is associated with poorer cognition, while also protecting against cognitive decline in older age. PURPOSE: We investigated whether body mass independently predicted cognition in older age and whether these associations changed over time. METHODS: A latent curve structural equation modeling approach was used to analyze data from a sample of aging adults (N = 8442) split into two independent subsamples, collected over 6 years. RESULTS: Lower baseline Body Mass Index (BMI) and higher physical activity independently predicted greater baseline cognition (p < 0.001). Decreases in BMI and physical activity independently predicted greater decline in the slope of cognition (p < 0.001). CONCLUSIONS: Our results support the obesity paradox in cognitive aging, with lower baseline body mass predicting better cognition, but less decline over time protecting against cognitive decline. We discuss how weight loss in the elderly may serve as a useful indicator of co-occurring cognitive decline, and we discuss implications for health care professionals.

A dyadic approach to health, cognition, and quality of life in aging adults.

Married couples evidence interdependence in their psychological and physical wellbeing across the life span. This is particularly true in aging populations that experience declines in physical health and cognitive ability. This study investigated the effects of partners' physical health and cognition on quality of life (QoL) in a series of bivariate latent curve growth models. The sample included aging married couples (N = 8,187) who participated in the Survey of Health, Ageing, and Retirement in Europe (SHARE) study and provided data across 6 years. Results indicated that husbands' and wives' baseline levels and rates of change in QoL covaried significantly over time. In addition, husbands' and wives' physical health and cognition predicted their partners' baseline level of QoL above and beyond their own health and cognition, and these effects were of equivalent size for both men and women. The findings suggest that as couples age, husbands' and wives' QoL, cognition, and health are predictive of their partners' QoL.