In a Yes/No object recognition memory test with similar lures, older adults typically exhibit elevated rates of false recognition. However, the contributions of impaired retrieval, relative to reduced availability of target details, are difficult to disentangle using such a test. The present investigation sought to decouple these factors by comparing performance on a Yes/No (YN) test to that on a Forced Choice (FC) test, which minimizes demands on strategic retrieval processes, enabling a more direct measure of the availability of object details. Older adults exhibited increased lure false recognition across test formats (Experiment 1), suggesting a decline in the availability of object details contributes to deficits in performance. Manipulating interference by varying the number of objects studied selectively enhanced performance in the FC test, resulting in matched performance across groups, whereas age differences in YN performance persisted (Experiment 2), indicating an additional contribution of impaired strategic retrieval. Consistent with differential sensitivity of test format to strategic retrieval and the quality of stimulus representations among older adults, variability in the quality of object representations, measured using a perceptual discrimination task, was selectively related to FC performance. In contrast, variability in memory control processes, as measured with tests of recall and executive function, was related to performance across test formats. These results suggest that both declines in the availability of object details and impaired retrieval of object details contribute to elevated rates of lure false recognition with age, and highlight the utility of test format for dissociating these factors in memory-impaired populations.

Mnemonic discrimination deficits, or impaired ability to discriminate between similar events in memory, is a hallmark of cognitive aging, characterised by a stark age-related increase in false recognition. While individual differences in mnemonic discrimination have gained attention due to potential relevance for early detection of Alzheimer's disease, our understanding of the component processes that contribute to variability in task performance across older adults remains limited. The present investigation explores the roles of representational quality, indexed by perceptual discrimination of objects and scenes with overlapping features, and strategic retrieval ability, indexed by standardised tests of executive function, to mnemonic discrimination in a large cohort of older adults ( N =124). We took an individual differences approach and characterised the contributions of these factors to performance under Forced Choice (FC) and Yes/No (YN) recognition memory formats, which place different demands on strategic retrieval. Performance in both test formats declined with age. Accounting for age, individual differences in FC memory performance were best explained by perceptual discrimination score, whereas YN memory performance was best explained by executive functions. A linear mixed model and dominance analyses confirmed the relatively greater importance of perceptual discrimination over executive functioning for FC performance, while the opposite was true for YN. These findings highlight parallels between perceptual and mnemonic discrimination in aging, the importance of considering demands on executive functions in the context of mnemonic discrimination, and the relevance of test format for modulating the impact of these factors on performance in older adults.

Older adults show hyper- (or excessive) binding effects for simultaneously and sequentially presented distraction. Here, we addressed the potential role of hyper-binding in paired-associate learning. Older and younger adults learned a list of word pairs and then received an associative recognition task in which rearranged pairs were formed from items that had originally occurred either close together or far apart in the study list. Across 3 experiments, older adults made more false alarms to near re-pairings than to far re-pairings. Younger adults, on the other hand, showed no difference in false alarms to the 2 types of rearranged pairs. These findings may be tied to the greater tendency of older adults to maintain access to recently attended information, inadvertently forming broader associations across time, than is the case for younger adults.

Mounting behavioral evidence suggests that declines in both representational quality and controlled retrieval processes contribute to episodic memory decline with age. The present study sought neural evidence for age-related change in these factors by measuring neural differentiation during encoding of paired associates and changes in regional blood oxygenation level—dependent activity and functional connectivity during retrieval conditions that placed low (intact pairs) and high (recombined pairs) demands on controlled retrieval processes. Pattern similarity analysis revealed age-related declines in the differentiation of stimulus representations at encoding, manifesting as both reduced pattern similarity between closely related events and increased pattern similarity between distinct events. During retrieval, both groups increased recruitment of areas within the core recollection network when endorsing studied pairs, including the hippocampus and angular gyrus. In contrast, only younger adults increased recruitment of, and hippocampal connectivity with, lateral prefrontal regions during correct rejections of recombined pairs. These results provide evidence for age-related changes in representational quality and in the neural mechanisms supporting memory retrieval under conditions of high, but not low, control demand.

Age-related episodic memory decline is characterized by striking heterogeneity across individuals. Hippocampal pattern completion is a fundamental process supporting episodic memory. Yet, the degree to which this mechanism is impaired with age, and contributes to variability in episodic memory, remains unclear. We combine univariate and multivariate analyses of fMRI data from a large cohort of cognitively normal older adults (N=100) to measure hippocampal activity and cortical reinstatement during retrieval of trial-unique associations. Trial-wise analyses revealed that (a) hippocampal activity scaled with reinstatement strength, (b) cortical reinstatement partially mediated the relationship between hippocampal activity and associative retrieval, (c) older age weakened cortical reinstatement and its relationship to memory behaviour. Moreover, individual differences in the strength of hippocampal activity and cortical reinstatement explained unique variance in performance across multiple assays of episodic memory. These results indicate that fMRI indices of hippocampal pattern completion explain within- and across-individual memory variability in older adults.

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Purpose In vivo measurement of the spatial distribution of neurofibrillary tangle pathology is critical for early diagnosis and disease monitoring of Alzheimer's disease (AD). Methods Forty-nine participants were scanned with 18 F-PI-2620 PET to examine the distribution of this novel PET ligand throughout the course of AD: 36 older healthy controls (HC) (age range 61 to 86), 11 beta-amyloid+ (Aβ+) participants with cognitive impairment (CI; clinical diagnosis of either mild cognitive impairment or AD dementia, age range 57 to 86), and 2 participants with semantic variant primary progressive aphasia (svPPA, age 66 and 78). Group differences in brain regions relevant in AD (medial temporal lobe, posterior cingulate cortex, and lateral parietal cortex) were examined using standardized uptake value ratios (SUVRs) normalized to the inferior gray matter of the cerebellum. Results SUVRs in target regions were relatively stable 60 to 90 min post-injection, with the exception of very high binders who continued to show increases over time. Robust elevations in 18 F-PI-2620 were observed between HC and Aβ+ CI across all AD regions. Within the HC group, older age was associated with subtle elevations in target regions. Mildly elevated focal uptake was observed in the anterior temporal pole in one svPPA patient. Conclusion Preliminary results suggest strong differences in the medial temporal lobe and cortical regions known to be impacted in AD using 18 F-PI-2620 in patients along the AD trajectory. This work confirms that 18 F-PI-2620 holds promise as a tool to visualize tau aggregations in AD.

Objective:To determine if memory tasks with demonstrated sensitivity to hippocampal function can detect variance related to preclinical Alzheimer’s disease (AD) biomarkers, we examined associations between performance in three memory tasks and CSF Aβ42/Aβ40 and p-tau181 in cognitively unimpaired older adults (CU).Methods:CU enrolled in the Stanford Aging and Memory Study (N=153; age 68.78 ± 5.81 yrs; 94 female) completed a lumbar puncture and memory assessments. CSF Aβ42, Aβ40, and phosopho-tau181 (p-tau181) were measured with the automated Lumipulse G system in a single-batch analysis. Episodic memory was assayed using a standardized delayed recall composite, paired associate (word-picture) cued recall, and a mnemonic discrimination task that involves discrimination between studied ‘target’ objects, novel ‘foil’ objects, and perceptually similar ‘lure’ objects. Analyses examined cross-sectional relationships between memory performance, age, and CSF measures, controlling for sex and education.Results:Age and lower Aβ42/Aβ40 were independently associated with elevated p-tau181. Age, Aβ42/Aβ40, and p-tau181 were each associated with a) poorer associative memory and b) diminished improvement in mnemonic discrimination performance across levels of decreased task difficulty (i.e., target-lure similarity). P-tau mediated the effect of Aβ42/Aβ40 on memory. Relationships between CSF proteins and delayed recall were similar but non-significant. CSF Aβ42 was not significantly associated with p-tau181 or memory.Conclusions:Tests designed to tax hippocampal function are sensitive to subtle individual differences in memory among CU, and correlate with early AD-associated biomarker changes in CSF. These tests may offer utility for identifying cognitively unimpaired older adults with preclinical AD pathology.