Face-name Associative Memory Research Articles

Associations between accelerated forgetting, amyloid deposition and brain atrophy in older adults.

Accelerated long-term forgetting (ALF) is the phenomenon whereby material is retained normally over short intervals (e.g. minutes) but forgotten abnormally rapidly over longer periods (days or weeks). ALF may be an early marker of cognitive decline, but little is known about its relationships with preclinical Alzheimer's disease pathology, and how memory selectivity may influence which material is forgotten. We assessed ALF in 'Insight 46', a sub-study of the MRC National Survey of Health and Development (a population-based cohort born during one week in 1946) (n=429; 47% female; assessed aged ∼73 years). ALF assessment comprised visual and verbal memory tests: Complex Figure Drawing and the Face-Name Associative Memory Exam (FNAME). ALF scores were calculated as the percentage of material retained after 7 days, relative to 30 minutes. In 306 cognitively-normal participants, we investigated effects on ALF of β-amyloid pathology (quantified using 18F-Florbetapir-PET, classified as positive/negative) and whole-brain and hippocampal atrophy rate (quantified from serial T1-MRI over ∼2.4 years preceding the ALF assessment), as well as interactions between these pathologies. We categorized Complex Figure Drawing items as 'outline' or 'detail', to test our hypothesis that forgetting the outline of the structure would be more sensitive to the effect of brain pathologies. We also investigated associations between ALF and Subjective Cognitive Decline, measured with the MyCog questionnaire. Complex Figure 'outline' items were better retained than 'detail' items (mean retention over 7 days = 94% vs 72%). Amyloid-positive participants showed greater forgetting of the Complex Figure outline, compared to amyloid-negatives (90% vs 95%; P<0.01). There were interactions between amyloid pathology and cerebral atrophy, such that whole-brain and hippocampal atrophy predicted greater ALF on Complex Figure Drawing among amyloid-positives only (e.g. 1.9 percentage-points lower retention per ml/year of whole-brain atrophy [95% confidence intervals 0.5, 3.7]; P<0.05). Greater ALF on FNAME was associated with increased rate of hippocampal atrophy. ALF on Complex Figure Drawing also correlated with subjective cognitive decline (-0.45 percentage-points per MyCog point [-0.85, -0.05], P<0.05). These results provide evidence of associations between some measures of ALF and biomarkers of brain pathologies and subjective cognitive decline in cognitively-normal older adults. On Complex Figure Drawing, 'outline' items were better remembered than 'detail' items - illustrating the strategic role of memory selectivity - but 'outline' items were also relatively more vulnerable to ALF in individuals with amyloid pathology. Overall, our findings suggest that ALF may be a sensitive marker of cognitive changes in preclinical Alzheimer's disease.

Change in Digital Cognitive Test Performance between Solanezumab and Placebo Groups in Preclinical Alzheimer’s Disease: Secondary Analyses from the A4 Study

BackgroundPrimary results from the Anti-Amyloid in Asymptomatic Alzheimer’s disease Study (A4) suggested no benefit of solanezumab on its primary cognitive outcome, a composite of paper and pencil tests (the Preclinical Alzheimer’s Cognitive Composite; PACC).ObjectiveTo determine whether change in cognitive performance, assessed using the Computerized Cognitive Composite (C3) summary score and C3 individual tests, differed between treatment groups over 240 weeks, differed based on baseline Aβ burden, and tracked with PACC decline.DesignLongitudinal analysis of cognitive change over 240 weeks on the C3 Summary Score and C3 individual tests between participants randomly assigned to solanezumab at a dose of up to 1600 mg intravenously every 4 weeks versus placebo.SettingThe A4 study took place at 67 sites in Australia, Canada, Japan and the United States.ParticipantsCognitively unimpaired older adults (n=1117, Mean Age=71.9, 60.7% female) with elevated brain amyloid levels on 18F-florbetapir positron-emission tomography (PET) at baseline (n=549 in the solanezumab group; n=568 in the placebo group).MeasurementsParticipants completed the C3 battery and PACC every 6 months. The C3 Summary Score combines the Cogstate Brief Battery (CBB)-One Card Learning, the Behavioral Pattern Separation (BPS) Test- Object- Lure Discrimination Index, and the Face Name Associative Memory Exam (FNAME)- Face-Name Matching.ResultsChange on the C3 Summary Score was moderately correlated with change on the PACC (Spearman’s corr=0.53, 95% CI: 0.49 to 0.57; p<0.001). At 240 weeks, mean change in the C3 Summary Score did not differ between groups; +0.24 in the solanezumab group and +0.27 in the placebo group (mean difference= −0.02; 95% CI: −0.13 to 0.08; p = 0.650). Lack of a treatment effect was similarly observed across most individual C3 tests. Performance on the C3 tests were influenced by level of amyloid burden, where higher levels were associated with worse performance.ConclusionThis study provides corroborating evidence that solanezumab does not slow cognitive decline in preclinical AD as exhibited with a computerized cognitive assessment with some evidence that solanezumab may exacerbate cognition on select digital outcomes. This study also provides important information that amyloid related cognitive change manifests differently on individual C3 tests.

Performance on the Latin American version of the Face-Name Associative Memory Exam (LAS-FNAME) distinguishes individuals with Mild Cognitive Impairment from age-matched controls in a sample from Argentina

Introduction The Latin American Spanish version of the Face-Name Associative Memory Exam (LAS-FNAME) has shown promise in identifying cognitive changes in those at risk for Alzheimer’s disease (AD). However, its applicability for Mild Cognitive Impairment (MCI) detection in the Latin American population remains unexplored. This study aims to analyze the psychometric properties in terms of validity and reliability and diagnostic performance of the LAS-FNAME for the detection of memory disorders in patients with amnestic MCI (aMCI). Materials and methods The study included 31 participants with aMCI, diagnosed by a neurologist according to Petersen’s criteria, and 19 healthy controls. Inclusion criteria for the aMCI group were to be 60 years of age or older, report cognitive complaints, have a memory test score (Craft Story 21) below a -1.5 z-score and have preserved functioning in activities of daily living. Participants completed LAS-FNAME and a comprehensive neuropsychological assessment. Results LAS-FNAME showed the ability to discriminate against healthy controls from patients with aMCI (AUC= 75) in comparison with a gold-standard memory test (AUC = 69.1). LAS-FNAME also showed evidence of concurrent and divergent validity with a standard memory test (RAVLT) (r = 0.58, p < .001) and with an attention task (Digit Span) (r = −0.37, p = .06). Finally, the reliability index was very high (α = 0.88). Discussion LAS-FNAME effectively distinguished aMCI patients from healthy controls, suggesting its potential for detecting early cognitive changes in Alzheimer’s prodromal stages among Spanish speakers.

92 Biber Figure Learning Test Outperforms Other Cognitive Measures in Predicting Subjective Cognitive Decline

Objective:Subjective Cognitive Decline (SCD), the perception of deteriorating cognition in the absence of apparent impairment on objective testing, has gained momentum in recent literature as a risk marker for AD. Traditional neuropsychological assessments, while typically inclusive of a word list learning task, often do not include a comparable figure learning task. Growing evidence suggests that nonverbal assessments may be particularly sensitive to the earliest cognitive changes associated with Alzheimer’s disease. The Biber Figure Learning Test (BFLT), a visuospatial analogue to verbal list learning tasks, has been shown to associate with brain-based biomarkers of Alzheimer’s disease (AD; hippocampal volume, amyloid load). This study investigates the utility of the BFLT in capturing SCD above and beyond other cognitive measures sensitive to AD progression.Participants and Methods:50 community-dwelling, cognitively normal individuals (78% White, 16% Black, 6% Other; 92% Non-Hispanic; 64% Female; Education M=17.1, SD=2.1; Age M=72.7, SD=6.2) participated in a study of SCD. All participants performed &gt;-1.5 SD on clinical neuropsychological testing including a word list learning task. SCD was assessed using a 20-item scale querying individuals’ perception of difficulty across a range of memory and non-memory abilities in relation to others of the same age. Participants completed the BFLT, Loewenstein-Acevedo Scales of Semantic Interference and Learning (LASSI-L), Short-Term Memory Binding (STMB), and Face-Name Associative Memory Exam (FNAME), previously established as being sensitive to pre-clinical AD, were examined as predictors of SCD. A multiple regression adjusted for demographics (age, gender, education) was used to investigate the extent to which BFLT Trial 1 (T1) predicted SCD above and beyond these other cognitive measures sensitive to AD progression. Trial 1 of the BFLT was used based on a separate abstract examining which BFLT score was most highly associated with SCD (Kann et al., pending acceptance).Results:Adjusting for demographics, the present model accounts for 42% of the variance in SCD, while Biber T1 alone accounts for 20% and is the only significant individual predictor of SCD (β=-0.55, p=0.004). In contrast, other variables in the model independently accounted for less than 1% to 4% each (age β=-0.23, p=0.15; gender β=-0.15, p=0.34; education β=0.06, p=0.66; LASSI-L β=-0.11, p=0.55; STMB β=-0.03, p=0.85; FNAME β=-0.10, p=0.64).Conclusions:The present study demonstrates the usefulness of the first learning trial of the BFLT as an independent predictor of SCD above and beyond other verbal and nonverbal measures sensitive to AD pathology. It also highlights the value of including even one trial of figure learning (&lt; 5 minutes) in both clinical and research assessments seeking to capture cognitive changes which may be the earliest indicators of a neurodegenerative process. Ongoing longitudinal research is examining the predictive utility of the BFLT for future cognitive decline and transition to Mild Cognitive Impairment. Further research should explore the association between Biber T1, specifically, and neuropathological biomarkers of AD to further establish its utility as a portent of AD.

Sex-dependent alterations in hippocampal connectivity are linked to cerebrovascular and amyloid pathologies in normal aging.

Compared to males, females have an accelerated trajectory of cognitive decline in Alzheimer's disease (AD). The neurobiological factors underlying the more rapid cognitive decline in AD in females remain unclear. This study explored how sex-dependent alterations in hippocampal connectivity over 2 years are associated with cerebrovascular and amyloid pathologies in normal aging. Thirty-three females and 21 males 65 to 93 years of age with no cognitive impairment performed a face-name associative memory functional magnetic resonance imaging (fMRI) task with a 2-year follow-up. We acquired baseline carbon 11-labeled Pittsburgh compound B ([11 C]PiB) positron emission tomography (PET) and T2-weighted fluid-attenuated inversion recovery (T2-FLAIR) MRI to quantify amyloid β (Aβ) burden and white matter hyperintensity (WMH) volume, respectively. Males had increased hippocampal-prefrontal connectivity over 2 years, associated with greater Aβ burden. Females had increased bilateral hippocampal functional connectivity, associated with greater WMH volume. These findings suggest sex-dependent compensatory mechanisms in the memory network in the presence of cerebrovascular and AD pathologies and may explain the accelerated trajectory of cognitive decline in females.

A novel face-name mnemonic discrimination task with naturalistic stimuli

Difficulty remembering faces and names is a common struggle for many people and gets more difficult as we age. Subtle changes in appearance from day to day, common facial characteristics across individuals, and overlap of names may contribute to the difficulty of learning face-name associations. Computational models suggest the hippocampus plays a key role in reducing interference across experiences with overlapping information by performing pattern separation, which enables us to encode similar experiences as distinct from one another. Thus, given the nature of overlapping features within face-name associative memory, hippocampal pattern separation may be an important underlying mechanism supporting this type of memory. Furthermore, cross-species approaches find that aging is associated with deficits in hippocampal pattern separation. Mnemonic discrimination tasks have been designed to tax hippocampal pattern separation and provide a more sensitive measure of age-related cognitive decline compared to traditional memory tasks. However, traditional face-name associative memory tasks do not parametrically vary overlapping features of faces and names to tax hippocampal pattern separation and often lack naturalistic facial features (e.g., hair, accessories, similarity of features, emotional expressions). Here, we developed a face-name mnemonic discrimination task where we varied face stimuli by similarity, race, sex, and emotional expression as well as the similarity of name stimuli. We tested a sample of healthy young and older adults on this task and found that both age groups showed worsening performance as face-name interference increased. Overall, older adults struggled to remember faces and face-name pairs more than young adults. However, while young adults remembered emotional faces better than neutral faces, older adults selectively remembered positive faces. Thus, the use of a face-name association memory task designed with varying levels of face-name interference as well as the inclusion of naturalistic face stimuli across race, sex, and emotional expressions provides a more nuanced approach relative to traditional face-name association tasks toward understanding age-related changes in memory.

Extended FNAME performance is preserved in subjective cognitive decline but highly affected in amnestic mild cognitive impairment.

The cognitive characterization of Alzheimer's disease risk states, such as amnestic mild cognitive impairment (aMCI) and subjective cognitive decline (SCD), is fundamental for timely diagnosis and interventions. The Face Name Associative Memory Exam (FNAME) is sensitive to early Alzheimer's disease brain changes, and an extended version captures a fuller range of associative memory abilities. We aimed to assess group effects in the extended FNAME in older adults with SCD, aMCI, and older adult controls (CON). Two concurrently created versions of the extended FNAME were used to test three groups of older adults (CON = 35, SCD = 37, aMCI = 31) at two sites (Mexico = 59, Netherlands = 44). Extended FNAME memory abilities were analyzed in five analyses of variance. Group and site were considered as independent variables. For the recall ability, subtest levels were entered as a within-subject variable. The remaining abilities (Face Recognition, Name Recognition, Spontaneous Name Recall, and Face-Name Matching) were analyzed in independent models. In all models, the main effect for group was significant with large effect sizes, driven by a worse performance of aMCI participants. No significant differences were found between SCD and CON. The main effect for site was only significant in Face Recognition. The worse performance of aMCI in the extended FNAME implies an impairment in associative memory abilities beyond recall. The similar performance of CON and SCD might be explained by the recruitment of SCD participants that did not spontaneously seek help for memory decline. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

The diagnostic usefulness of experimental memory tasks for detecting subjective cognitive decline: Preliminary results in an Italian sample.

Subjective cognitive decline (SCD) was recently proposed as an early risk factor for future mild cognitive impairment and Alzheimer's disease (AD). In this study, we investigated the sensitivity of novel neuropsychological testing paradigms (which have been proposed as potentially challenging tools for the identification of preclinical AD) in capturing the subtle cognitive changes leading to SCD but not objectively detected by traditional tests. The performances of 18 patients with SCD and 15 healthy individuals with no worries of cognitive decline (healthy controls [HC]) was compared on demanding tasks that investigated, respectively, associative memory, memory binding, spatial pattern separation processes and semantic memory. The diagnostic utility of these tests in capturing the subtle cognitive changes associated with SCD and possible relationships with SCD-related worries were investigated. No significance between-group difference was found on the standard neuropsychological tests. Conversely, the performance of patients with SCD and HC differed significantly on specific indexes derived from experimental tasks assessing face-name associative memory and spatial pattern separation. Moreover, these measures correctly classified group membership with good overall accuracy (between 79% and 82%) and were significantly associated with self-perceived memory functioning. Our preliminary findings suggest that specific measures derived from demanding cognitive paradigms could be sensitive neuropsychological indexes for detecting the subtle cognitive impairment associated with SCD. These observations could be useful for further refining cognitive assessment aimed at early detection of AD. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Intersubject similarity in neural representations underlies shared episodic memory content

Individuals generally form their unique memories from shared experiences, yet the neural representational mechanisms underlying this subjectiveness of memory are poorly understood. The current study addressed this important question from the cross-subject neural representational perspective, leveraging a large functional magnetic resonance imaging dataset (n = 415) of a face-name associative memory task. We found that individuals' memory abilities were predicted by their synchronization to the group-averaged, canonical trial-by-trial activation level and, to a lesser degree, by their similarity to the group-averaged representational patterns during encoding. More importantly, the memory content shared between pairs of participants could be predicted by their shared local neural activation pattern, particularly in the angular gyrus and ventromedial prefrontal cortex, even after controlling for differences in memory abilities. These results uncover neural representational mechanisms for individualized memory and underscore the constructive nature of episodic memory.

Women’s Brain Health: Midlife Ovarian Removal Affects Associative Memory

Women with early bilateral salpingo-oophorectomy (BSO; removal of ovaries and fallopian tubes) have greater Alzheimer’s disease (AD) risk than women in spontaneous/natural menopause (SM), but early biomarkers of this risk are not well-characterized. Considering associative memory deficits may presage preclinical AD, we wondered if one of the earliest changes might be in associative memory and whether younger women with BSO had changes similar to those observed in SM. Women with BSO (with and without 17β-estradiol replacement therapy (ERT)), their age-matched premenopausal controls (AMC), and older women in SM completed a functional magnetic resonance imaging face-name associative memory task shown to predict early AD. Brain activation during encoding was compared between groups: AMC (n=25), BSO no ERT (BSO; n=15), BSO+ERT (n=16), and SM without hormone therapy (n=16). Region-of-interest analyses revealed AMC did not contribute to functional group differences. BSO+ERT had higher hippocampal activation than BSO and SM. This hippocampal activation correlated positively with urinary metabolite levels of 17β-estradiol. Multivariate partial least squares analyses showed BSO+ERT had a different network-level activation pattern than BSO and SM. Thus, despite being approximately 10 years younger, women with BSO without ERT had similar brain function to those with SM, suggesting early 17β-estradiol loss may lead to an altered functional brain phenotype which could influence late-life AD risk, making face-name encoding a potential biomarker for midlife women with increased AD risk. Despite similarities in activation, BSO and SM groups showed opposite within-hippocampus connectivity, suggesting menopause type is an important consideration when assessing brain function.

Face Name Associative Memory Exam and biomarker status in the ARMADA study: Advancing reliable measurement in Alzheimer's disease and cognitive aging.

The Face Name Associative Memory Exam (FNAME) was introduced into the NIH Toolbox as part of the ARMADA study and establishes normative data for diverse participants, ages 64 to 85+, and proposes cutoff scores between biomarker positive versus negative (+/-) groups. The FNAME was administered to 257 participants across the clinical spectrum with 122 having amyloid biomarkers. Linear regression explored the association between demographics and FNAME and between amyloid (+/-) groups. Receiver operating characteristic curves (ROC) identified performance thresholds that best discriminated between biomarker (+/-) individuals. Lower FNAME scores occurred in males, older ages, Black/African Americans, Hispanics, and biomarker-positive participants. ROC analyses demonstrated acceptable accuracy (0.73 to 0.77) but only when combined with clinical status. The diagnostic discrimination of amyloid positivity was acceptable but not excellent, suggesting the FNAME may be a better screening indicator of clinical status rather than amyloid deposition in cognitively normal individuals. Normative data are provided.

Evidence for the role of affective theory of mind in face-name associative memory

ABSTRACT Poor face-name recall has been associated with age-related impairments in cognitive functioning, namely declines in episodic memory and executive control. However, the role of social cognitive function – the ability to remember, process, and store information about others – has been largely overlooked in this work. Extensive work has shown that social and nonsocial cognitive processes rely on unique, albeit overlapping, mechanisms. In the current study, we explored whether social cognitive functioning – specifically the ability to infer other people’s mental states (i.e., theory of mind) – facilitates better face-name learning. To do this, a sample of 289 older and young adults completed a face-name learning paradigm along with standard assessments of episodic memory and executive control alongside two theory of mind measures, one static and one dynamic. In addition to expected age differences, several key effects emerged. Age-related differences in recognition were explained by episodic memory, not social cognition. However, age effects in recall were explained by both episodic memory and social cognition, specifically affective theory of mind in the dynamic task. Altogether, we contend that face-name recall can be supported by social cognitive functioning, namely understanding emotions. While acknowledging the influence of task characteristics (i.e., lures, target ages), we interpret these findings in light of existing accounts of age differences in face-name associative memory.

A comprehensive assessment of age at menopause with well-characterized cognition at 70 years: A population-based British birth cohort

ObjectivesAssociations between age at menopause and cognition post-menopause are examined to determine whether relationships are stronger for certain cognitive domains. Study designWomen from the Medical Research Council National Survey of Health and Development and its neuroscience sub-study, Insight 46, were included if they had known age at menopause (self-reported via questionnaire) and complete cognitive outcome data at age 69 (n = 746) or at Insight 46 wave I (n = 197). Multivariable linear regression analyses adjusting for life course confounders were run; interactions with menopause type (natural/surgical) and APOE-ε4 status were examined; and the potential contribution of hormone therapy was assessed. Main outcome measuresCognitive measures were standardized Addenbrooke's Cognitive Examination - third edition total and sub-domain scores at age 69 (whole cohort) and Preclinical Alzheimer's Cognitive Composite total and sub-test scores at age ~70 (Insight 46). ResultsOlder age at menopause was associated with better performance across all outcomes, most strongly for the Addenbrooke's Cognitive Examination memory and visuospatial function sub-domains, and the Preclinical Alzheimer's Cognitive Composite digit-symbol substitution test and face-name associative memory examination sub-tests. Adjusting for early-life factors attenuated all effect estimates, driven by childhood cognition, and accounting for menopause type revealed negative confounding for some outcomes. No significant interactions with menopause type or APOE-ε4 status were detected. Further adjustment for hormone therapy did not meaningfully alter the estimated effects. ConclusionsOlder age at menopause is associated with better later-life cognitive performance, particularly for visual processing and associative learning and memory domains. Childhood cognition was an important contributor.

Short‐term cognitive practice effects and their relation to amyloid and tau in preclinical Alzheimer’s disease

AbstractBackgroundIdentification of cognitive paradigms that relate to biomarker evidence of Alzheimer’s disease (AD), such as tau, can greatly enhance patient selection for clinical trials. Computerized cognitive assessments that can be frequently administered may yield multiple unique variables that can improve detection of subtle cognitive decline in preclinical AD. Indeed, practice effects (i.e., improved performance on repeated testing) are diminished in clinically unimpaired older adults with abnormal amyloid, but their relations with tau are unknown. Here, we determine whether baseline performance and practice effects at 3 months re‐testing on the Computerized Cognitive Composite (C3) relate to medial temporal lobe (MTL) tau.MethodWe examined 390 clinically unimpaired older adults from the A4 study with tau PET (flortaucipir) imaging who completed two C3 assessments pre‐study randomization. C3 assessments were completed approximately 90 days apart and included pattern separation [Behavioral Pattern Separation Test – Object (BPS‐O)], associative memory [Face Name Associative Memory Exam (FNAME)], and visual memory [One‐Card Learning (OCL)]. C3 baseline performance and practice effects (change in performance from Assessment 1 to 2) were examined in relation to continuous amyloid and MTL tau burden.ResultGreater amyloid burden was significantly associated with lower baseline C3 scores (B(SE) = ‐0.86 (0.24), p&lt;0.001) but not C3 practice effects (B(SE) = ‐0.09 (0.23), p = 0.702). In contrast, greater tau in the MTL was significantly associated with reduced C3 practice effects (B(SE) = ‐0.49 (0.21), p = 0.023) and marginally associated with baseline C3 performance (B(SE) = ‐0.37 (0.22), p = 0.099) while controlling for continuous amyloid and demographic variables. Further examination of C3 subtests revealed that pattern separation (BPS‐O; B(SE) = ‐0.70 (0.34), p = 0.039) and associative memory (FNAME; B(SE) = ‐1.13 (0.42), p = 0.007) were driving MTL tau associations with C3 practice effects.ConclusionDiminished practice effects on memory‐based measures are associated with elevated MTL tau burden in preclinical AD. Furthermore, diminished practice effects offer a unique signal above and beyond cross‐sectional performance. For clinical trials, examination of practice effects on computerized assessments over a short timescale may be a cost‐effective method to facilitate identification of those with biomarker evidence of AD.

Face name matching and memory complaints in Parkinson's disease.

Memory impairment is a hallmark cognitive deficit in Parkinson's disease (PD). However, it remains unclear which processes underlie this deficit in PD. Also, little is known on these patients' subjective experiences of memory difficulties and their relationship with objective measures. We aim to portray memory deficits in PD by combining objective and subjective memory measures. Fifteen PD patients and 15 controls were assessed with an extended version of the Face-Name Associative Memory Exam (FNAME) and the Memory Failures of Everyday Questionnaire (MFE-28). We also explored the relationship among clinical and cognitive variables. Participants with PD presented with more memory complaints. On the FNAME, these patients exhibited lower performance in free recall, as well as in name recognition and matching. Importantly, when controlling for initial learning, group effects disappeared, except for matching. Associative memory therefore was significantly compromised in PD and correlated with subjective memory complaints (SMC). Our findings suggest that associative memory may constitute a sensitive measure to detect subtle memory deficits in PD. Moreover, the current study further clarifies the source of memory impairment in PD. Thus, our study highlights the clinical value of including associative memory tests such as the FNAME in PD neuropsychological assessment.

Higher-dimensional neural representations predict better episodic memory.

Episodic memory enables humans to encode and later vividly retrieve information about our rich experiences, yet the neural representations that support this mental capacity are poorly understood. Using a large fMRI dataset (n = 468) of face-name associative memory tasks and principal component analysis to examine neural representational dimensionality (RD), we found that the human brain maintained a high-dimensional representation of faces through hierarchical representation within and beyond the face-selective regions. Critically, greater RD was associated with better subsequent memory performance both within and across participants, and this association was specific to episodic memory but not general cognitive abilities. Furthermore, the frontoparietal activities could suppress the shared low-dimensional fluctuations and reduce the correlations of local neural responses, resulting in greater RD. RD was not associated with the degree of item-specific pattern similarity, and it made complementary contributions to episodic memory. These results provide a mechanistic understanding of the role of RD in supporting accurate episodic memory.

Metabolic syndrome impact on cognitive composites domain scores and on white matter hyperintensities in subjective cognitive decline: The FACEHBI Cohort

AbstractBackgroundTo explore the impact of Metabolic Syndrome (MetS) and its components on Cognitive Composites (CCs) domain scores and on White Matter Hyperintensities (WMHs) in individuals experiencing Subjective Cognitive Decline (SCD).MethodTwo hundred participants from the FACEHBI cohort underwent structural Magnetic Resonance Imaging (MRI), 18F‐Florbetaben Positron Emission Tomography (FBB‐PET), and a comprehensive neuropsychological assessment. MetS was defined using the Joint Interim Statement of the International Diabetes Federation Task Force on Epidemiology and Prevention criteria (elevated fasting glucose, elevated blood pressure, reduced HDL‐C, elevated triglycerides and elevated waist circumference). WMHs were addressed through the Fazekas scale, the Age‐related white matter changes (ARWMC) scale, and the FreeSurfer pipeline. Ten CCs domain scores were created using principal components analysis (PCA): (1) executive function fluency, (2) executive function processing speed, (3) executive function attention, (4) verbal memory, (5) visual memory, (6) face–name associative memory, (7) face–occupation associative memory, (8) language, (9) visuoperception, and (10) praxis. Age, sex, education, and Apolipoprotein E (APOE) were used as adjusting variables. Several analyses were performed to explore a sex effect.ResultForty‐seven individuals matched the MetS criteria. This syndrome behaves differently based on sex. Only women with MetS showed better performance in language (p = .002; OR = 2.12) than those without MetS. The only differentiating component between both groups (presence/absence MetS) was that women in the MetS subgroup presented greater abdominal obesity (Mann‐Whitney p = .001). From Mets group, antihypertensive drug treatment was significantly associated with better praxis scores (p = .012; OR = 1.84) and HDL‐C drug treatment with better language scores but worse episodic memory performance (p = .028; OR = 1.60; and p = .007; OR = .57, respectively). Drug treatment for elevated glucose was associated with low WMH load in the ARWMC scale (β= ‐.144; p = .045).ConclusionThis study demonstrated a protective effect of MetS in cognitive performance among SCD women with greater abdominal obesity and a lack of association between MetS and WMH load, although further investigation is needed to explore the long term impact of its entity.

Tractography-guided hippocampal theta burst stimulation to improve memory performance and increase hippocampal connectivity in mild cognitive impairment

Abstract A personalized, image-guided theta-burst stimulation (TBS) protocol was developed for individuals with mild cognitive impairment (MCI). MCI is a transitional stage between normal aging and Alzheimer's disease (AD). There is a need for interventions to alleviate the deterioration of memory. Targeting the hippocampus, which still exhibits plasticity at the stage of MCI, may be an effective strategy to enhance memory functions. By using white matter tractography maps as a guide, we were able to effectively relay the modulation effects of the superficial TBS to the hippocampus. Nine right-handed older adults (aged 65 to 74 years old) classified as MCI based on the Uniform Data Set version 3 (UDS3) neuropsychological battery participated in our study. Diffusion-weighted images were acquired for each participant at baseline to determine the optimal superficial stimulation site. White matter tractography of the left hippocampus was generated using MRtrix. In this cross-over design, participants were exposed to each of these conditions twice: excitatory intermittent TBS (iTBS), inhibitory continuous TBS (cTBS), and sham stimulation. A minimum of 5 days separates each TBS session to avoid potential carry-over effects. Outcome measures including resting-state fMRI and the Face-Name associative memory test (FNAME) were acquired immediately before and after each TBS session. Excitatory iTBS significantly improved associative memory and increased resting-state functional connectivity along the inferior longitudinal fasciculus (ILF) to the hippocampus compared to the sham TBS. Individuals who had a greater increase in functional connectivity between subfields of the hippocampus (i.e., CA1 and hippocampal fissures) and the superficial stimulation site following active TBS had greater memory enhancement (p < 0.05). New insights are provided about TBS propagation along the ILF from the surface stimulation site to the hippocampus. This tractography-guided TBS may be a useful strategy to guide the design of future TBS protocols to treat MCI. Keywords: Transcranial magnetic stimulation, Tractography, Mild Cognitive Impairment, Memory

Combination of white matter hyperintensities and A\u03b2 burden is related to cognitive composites domain scores in subjective cognitive decline: the FACEHBI cohort

BackgroundTo explore whether the combination of white matter hyperintensities (WMHs) and amyloid-beta (Aβ) deposition is associated with worse cognitive performance on cognitive composites (CCs) domain scores in individuals with subjective cognitive decline (SCD).MethodsTwo hundred participants from the FACEHBI cohort underwent structural magnetic resonance imaging (MRI), 18F-florbetaben positron emission tomography (FBB-PET), and neuropsychological assessment. WMHs were addressed through the Fazekas scale, the Age-Related White Matter Changes (ARWMC) scale, and the FreeSurfer pipeline. Eight CCs domain scores were created using the principal component analysis (PCA). Age, sex, education, and apolipoprotein E (APOE) were used as adjusting variables.ResultsAdjusted multiple linear regression models showed that FreeSurfer (B − .245; 95% CI − .1.676, − .393, p = .016) and β burden (SUVR) (B − .180; 95% CI − 2.140, − .292; p = .070) were associated with face–name associative memory CCs domain score, although the latest one was not statistically significant after correction for multiple testing (p = .070). There was non-significant interaction of these two factors on this same CCs domain score (p = .54). However, its cumulative effects on face–name associative performance indicated that those individuals with either higher WMH load or higher Aβ burden showed the worst performance on the face–name associative memory CCs domain score.ConclusionsOur results suggest that increased WMH load and increased Aβ are independently associated with poorer episodic memory performance in SCD individuals, indicating a cumulative effect of the combination of these two pathological conditions in promoting lower cognitive performance, an aspect that could help in terms of treatment and prevention.

Worse associative memory recall in healthy older adults compared to young ones, a face-name study in Spain and Mexico

ABSTRACT Introduction The Face Name Associative Memory Exam (FNAME) is sensitive to associative memory changes early in the Alzheimer’s disease spectrum, but little is known about how healthy aging affects FNAME performance. We aimed to assess aging effects on an extended version of the test, which captures further associative memory abilities beyond the recall and recognition domains measured in the original version. Method We adapted FNAME versions in Spain and Mexico, adding new subtests (Spontaneous Name Recall, Face-Name Matching). We compared the performance of 21 young adults (YA) and 27 older adults (OA) in Spain, and 34 YA and 36 OA in Mexico. Recall was analyzed using a mixed-model ANOVA including subtest scores as dependent variables, age group as a fixed-factor independent variable, and recall subtest as a three-level repeated-measure independent variable. The rest of the associative memory domains were analyzed through t-tests comparing the performance of YA and OA. Results In Spain, we found significant effects for age group and recall subtest, with large effect sizes. The recognition subtests (Face Recognition, Name Recognition) displayed ceiling effects in both groups. The new subtests displayed medium-to-large effect sizes when comparing age groups. In Mexico, these results were replicated, additionally controlling for education. In both studies, recall performance improved after repeated exposures and it was sustained after 30 minutes in YA and OA. Conclusions We document, in two different countries, a clear aging pattern on the extended FNAME: regardless of education, OA remember fewer stimuli than YA through recall subtests. The new subtests provide evidence on associative memory changes in aging beyond recall.