Explore the vast range of titles available.

Objectives: Alzheimer’s disease (AD) typically eludes clinical detection for years, if not decades. The identification of subtle cognitive decline associated with preclinical AD would not only advance understanding of the disease, but also provide clinical targets to assess preventative and early intervention treatments. Disrupted retrieval of detailed episodic autobiographical memories may be a sensitive indicator of subtle cognitive decline, because this type of memory taxes a core neural network affected by preclinical AD neuropathology. Methods: To begin to address this idea, we assessed the episodic specificity of autobiographical memories retrieved by cognitively normal middle-aged and older individuals who are carriers of the apolipoprotein E ε4 allele – a population at increased risk for subtle cognitive decline related to neuropathological risk factors for AD. We compared the ε4 carriers to non-carriers of ε4 similar in age, education, and gender. Results: The ε4 carriers did not perform worse than the non-carriers on a comprehensive battery of neuropsychological tests. In contrast, as a group, the ε4 carriers generated autobiographical memories that were reduced in “internal” or episodic details relative to non-carriers. Conclusions: These findings support the notion that reduced autobiographical episodic detail generation may be a marker of subtle cognitive decline associated with AD. (JINS, 2018, 24, 1073–1183)

Human imagination has garnered growing interest in many fields. However, it remains unclear how to characterize different forms of imaginative thinking and how imagination differs between young and older adults. Here, we introduce a novel scoring protocol based on recent theoretical developments in the cognitive neuroscience of imagination to provide a broad tool with which to characterize imaginative thinking. The scoring protocol distinguishes between concrete/perceptual forms of imagination termed the “mind’s eye” and abstract/reflective forms of imagination termed the “mind’s mind.” The protocol also captures whether thoughts pertain to the self, others, or both. We applied this scoring protocol with high inter-rater reliability across two studies involving distinct participants and narrative-based imagination tasks. When compared to young adults, older adults showed a bias toward general content, which is a feature of the mind’s mind form of thinking while describing aloud their memories of specific, past events (Study 1). Further, older adults made fewer references to the self. In a separate study of only older adults (Study 2), increasing age was not associated with a bias toward the mind’s mind while describing specific past or future events. These results reveal that imaginative thinking can be characterized within the Mind’s Eye Mind’s Mind framework, with implications for understanding cognitively normal older age.

On continuous recognition tasks, changing the context objects are embedded in impairs memory. Older adults are worse on pattern separation tasks requiring identification of similar objects compared to younger adults. However, how contexts impact pattern separation in aging is unclear. The apolipoprotein (APOE) ϵ4 allele may exacerbate possible age-related changes due to early, elevated neuropathology. The goal of this study is to determine how context and APOE status affect pattern separation among younger and older adults. Older and younger ϵ4 carriers and noncarriers were given a continuous object recognition task. Participants indicated if objects on a Repeated White background, Repeated Scene, or a Novel Scene were old, similar, or new. The proportions of correct responses and the types of errors made were calculated. Novel scenes lowered recognition scores compared to all other contexts for everyone. Younger adults outperformed older adults on identifying similar objects. Older adults misidentified similar objects as old more than new, and the repeated scene exacerbated this error. APOE status interacted with scene and age such that in repeated scenes, younger carriers produced less false alarms, and this trend switched for older adults where carriers made more false alarms. Context impacted recognition memory in the same way for both age groups. Older adults underutilized details and over relied on holistic information during pattern separation compared to younger adults. The triple interaction in false alarms may indicate an even greater reliance on holistic information among older adults with increased risk for Alzheimer's disease.

Although central to well-being, functional and dysfunctional thoughts arise and unfold over time in ways that remain poorly understood. To shed light on these mechanisms, we adapted a “think aloud” paradigm to quantify the content and dynamics of individuals’ thoughts at rest. Across two studies, external raters hand coded the content of each thought and computed dynamic metrics spanning duration, transition probabilities between affective states, and conceptual similarity over time. Study 1 highlighted the paradigm’s high ecological validity and revealed a narrowing of conceptual scope following more negative content. Study 2 replicated Study 1’s findings and examined individual difference predictors of trait brooding, a maladaptive form of rumination. Across individuals, increased trait brooding was linked to thoughts rated as more negative, past-oriented and self-focused. Longer negative and shorter positive thoughts were also apparent as brooding increased, as well as a tendency to shift away from positive conceptual states, and a stronger narrowing of conceptual scope following negative thoughts. Importantly, content and dynamics explained independent variance, accounting for a third of the variance in brooding. These results uncover a real-time cognitive signature of rumination and highlight the predictive and ecological validity of the think aloud paradigm applied to resting state cognition.

Older adults typically perform worse on spatial navigation tasks, although whether this is due to degradation of memory or an impairment in using specific strategies has yet to be determined. An issue with some past studies is that older adults are tested on desktop-based virtual reality: a technology many report lacking familiarity with. Even when controlling for familiarity, these paradigms reduce the information-rich, three-dimensional experience of navigating to a simple two-dimensional task that utilizes a mouse and keyboard (or joystick) as means for ambulation. Here, we utilize a wireless head-mounted display and free ambulation to create a fully immersive virtual Morris water maze in which we compare the navigation of older and younger adults. Older and younger adults learned the locations of hidden targets from same and different start points. Across different conditions tested, older adults remembered target locations less precisely compared to younger adults. Importantly, however, they performed comparably from the same viewpoint as a switched viewpoint, suggesting that they could generalize their memory for the location of a hidden target given a new point of view. When we implicitly moved one of the distal cues to determine whether older adults used an allocentric (multiple landmarks) or beaconing (single landmark) strategy to remember the hidden target, both older and younger adults showed comparable degrees of reliance on allocentric and beacon cues. These findings support the hypothesis that while older adults have less precise spatial memories, they maintain the ability to utilize various strategies when navigating.

Episodic memory and executive function are two cognitive domains that have been studied extensively in older adults and have been shown to decline in normally-aging older individuals. However, one of the problems with characterizing cognitive changes in longitudinal studies has been separating effects attributable to normal aging from effects created by repeated testing or practice. In the present study, 166 people aged 65 and older were enrolled over several years and tested at least 3 times at variable intervals (M=3.2 yrs). The cognitive measures were composite scores. Each composite was made up of five neuropsychological tests, previously identified through factor analysis. For one pair of composite scores, variance attributable to age was removed from each subtest through regression analyses before z-scores were computed, creating two age-corrected composites. A second pair of composites were not age-corrected. Using linear mixed-effects models, we first explored retest effects for each cognitive domain, independent of age, using the age-corrected composites. We then modeled aging effects using the age-uncorrected composites after subtracting out retest effects. Results indicated significant retest effects for memory but not for executive function, such that memory performance improved across the three testing sessions. When these practice effects were removed from the age-uncorrected data, effects of aging were evident for both executive and memory function with significant declines over time. We also explored several individual difference variables including sex, IQ, and age at the initial testing session and across time. Although sex and IQ affected performance on both cognitive factors at the initial test, neither was related to practice effects, although young-older adults tended to benefit from practice to a greater extent than old-older adults. In addition, people with higher IQs showed slower age-related declines in memory, but no advantages in executive function. These findings suggest that a) aging affects both memory and executive function similarly, b) higher IQ, possibly reflecting cognitive reserve, may slow age-related declines in memory, and c) practice through repeated testing enhances performance in memory particularly in younger-older adults, and may therefore mask aging effects if not taken into account.

Homocysteine (Hcy) is a cardiovascular risk factor implicated in cognitive impairment and cerebrovascular disease but has also been associated with Alzheimer’s disease. In 160 healthy older adults (mean age = 69.66 ± 9.95 years), we sought to investigate the association of cortical brain volume with white matter hyperintensity (WMH) burden and a previously identified Hcy-related multivariate network pattern showing reductions in subcortical gray matter (SGM) volumes of hippocampus and nucleus accumbens with relative preservation of basal ganglia. We additionally evaluated the potential role of these brain imaging markers as a series of mediators in a vascular brain pathway leading to age-related cognitive dysfunction in healthy aging. We found reductions in parietal lobar gray matter associated with the Hcy-SGM pattern, which was further associated with WMH burden. Mediation analyses revealed that slowed processing speed related to aging, but not executive functioning or memory, was mediated sequentially through increased WMH lesion volume, greater Hcy-SGM pattern expression, and then smaller parietal lobe volume. Together, these findings suggest that volume reductions in parietal gray matter associated with a pattern of Hcy-related SGM volume differences may be indicative of slowed processing speed in cognitive aging, potentially linking cardiovascular risk to an important aspect of cognitive dysfunction in healthy aging.

Cardiorespiratory fitness (CRF), measured by VO 2 max, is an indicator of vascular functioning that can influence the integrity of brain microstructural white matter tracts in aging. How CRF is related to regional patterns of white matter bundles for magnetic resonance imaging (MRI) diffusion metrics (axial diffusivity, AD; radial diffusivity, RD; mean diffusivity, MD; fractional anisotropy, FA) has been less studied. We used a multivariate analysis method, the Scaled Subprofile Model (SSM), to identify network patterns of MRI tract-specific white matter integrity (WMI) for AD, RD, MD, and FA related to VO 2 max and to evaluate their relation to demographic, vascular health, and dementia risk factors in 167 cognitively unimpaired older adults, ages 50 to 88. We identified four CRF-related regional patterns of WMI characterized by enhanced integrity in commissural pathways that connect areas within anterior brain regions (prefrontal body of the corpus callosum), connect subcortical regions to one another (fornix), and include selected association tracts (arcuate fasciculus, superior longitudinal fasciculus). Greater white matter lesion load, in addition to age, was associated with reduced expression of all four CRF-WMI patterns, while high vascular risk level was further associated with reduced expression of the RD, MD, and FA patterns. The regional patterns of RD and FA were most strongly associated with CRF. The results suggest that in healthy older adults, enhanced CRF is differentially associated with regional patterns of WMI, which are related to age and further impacted by macrostructural white matter lesion load and vascular risk. These findings support the use of the multivariate SSM in identifying regional patterns of white matter tracts that may provide markers of brain aging and cerebrovascular health.

Hippocampal volume is particularly sensitive to the accumulation of total brain white matter hyperintensity volume (WMH) in aging, but how the regional distribution of WMH volume differentially impacts the hippocampus has been less studied. In a cohort of 194 healthy older adults ages 50–89, we used a multivariate statistical method, the Scaled Subprofile Model (SSM), to (1) identify patterns of regional WMH differences related to left and right hippocampal volumes, (2) examine associations between the multimodal neuroimaging covariance patterns and demographic characteristics, and (3) investigate the relation of the patterns to subjective and objective memory in healthy aging. We established network covariance patterns of regional WMH volume differences associated with greater left and right hippocampal volumes, which were characterized by reductions in left temporal and right parietal WMH volumes and relative increases in bilateral occipital WMH volumes. Additionally, we observed lower expression of these hippocampal-related regional WMH patterns were significantly associated with increasing age and greater subjective memory complaints, but not objective memory performance in this healthy older adult cohort. Our findings indicate that, in cognitively healthy older adults, left and right hippocampal volume reductions were associated with differences in the regional distribution of WMH volumes, which were exacerbated by advancing age and related to greater subjective memory complaints. Multivariate network analyses, like SSM, may help elucidate important early effects of regional WMH volume on brain and cognitive aging in healthy older adults.

The retrieval of autobiographical memories is an integral part of everyday social interactions. Prior laboratory research has revealed that older age is associated with a reduction in the retrieval of autobiographical episodic memories, and the ability to elaborate these memories with episodic details. However, how age-related reductions in episodic specificity unfold in everyday social contexts remains largely unknown. Also, constraints of the laboratory-based approach have limited our understanding of how autobiographical semantic memory is linked to older age. To address these gaps in knowledge, we used a smartphone application known as the Electronically Activated Recorder, or “EAR”, to unobtrusively capture real-world conversations over four days. In a sample of 102 cognitively normal older adults, we extracted instances where memories and future thoughts were shared by the participants, and we scored the shared episodic memories and future thoughts for their make-up of episodic and semantic detail. We found that older age was associated with a reduction in real-world sharing of autobiographical episodic and semantic memories. We also found that older age was linked to less episodically and semantically detailed descriptions of autobiographical episodic memories. Frequency and level of detail of shared future thoughts yielded weaker relationships with age, which may be related to the low frequency of future thoughts in general. Similar to laboratory research, there was no correlation between autobiographical episodic detail sharing and a standard episodic memory test. However, in contrast to laboratory studies, episodic detail production while sharing autobiographical episodic memories was weakly related to episodic detail production while describing future events, unrelated to working memory, and not different between men and women. Overall, our findings provide novel evidence of how older age relates to episodic specificity when autobiographical memories are assessed unobtrusively and objectively “in the wild”.