Latent trajectories of recent and delayed memory and their predictors: evidence from SHARE.

OBJECTIVES: Cognitive decline is common in the old age, but some evidence suggests it may already occur during adulthood. Previous studies have linked age, gender, educational attainment, depression, physical activity, and social engagement to better cognitive performance over time. However, most studies have used global measures of cognition, which could mask subtle changes in specific cognitive domains. The aim of this study is to examine trajectories of recent and delayed memory recall from a variable-centered perspective, in order to elucidate the impact of age, gender, educational attainment, depression, physical activity, and social engagement on recent and delayed memory both at initial time and across a 10-year period. DESIGN AND PARTICIPANTS: The sample was formed by 56,616 adults and older adults that participated in waves 4 to 8 of the Survey of Health, Aging and Retirement in Europe (SHARE). ANALYSES: We used latent growth modeling to establish latent recent and delayed memory trajectories, and then tested the effects of the aforementioned covariates on the latent intercept and slopes. RESULTS: Results showed that both recent and delayed recall display a quadratic trajectory of decline. All covariates significantly explained initial levels of immediate and delayed recall, but only a few had statistically significant effects on the slope terms. CONCLUSIONS: We discuss differences between present results and those previously reported in studies using a person-centered approach. This study provides evidence of memory decline during adulthood and old adulthood. Further, results provide support for the neural compensation reserve theory.

Excessive daytime sleepiness in young and middle-aged Chinese adults with obstructive sleep apnea: implications for cognitive dysfunction.

OBJECTIVE: The objective of this study was to investigate the effects of excessive daytime sleepiness (EDS) on cognitive function among Chinese young and middle-aged Chinese patients with obstructive sleep apnea (OSA). METHODS: Chinese adults struggling from moderate to severe OSA with apnea-hypopnea index (AHI) ≥ 15 events per hour and adults with primary snoring and mild OSA (AHI < 15 events per hour) were included in the study. The Epworth Sleepiness Scale measured hypersomnia, and cognitive function was assessed using the Mini-mental State Examination (MMSE) and Montreal Cognitive Assessment (MOCA). RESULTS: In comparison to the primary snoring and mild OSA group (n=635), the moderate to severe OSA group (n=1423) tended to be older men with higher scores on the Epworth Sleepiness Scale (ESS), as well as higher levels of oxygen desaturation (ODI) and a higher body mass index (BMI). Patients with moderate to severe OSA had fewer years of education, lower minimum arterial oxygen saturation (min-SaO2), and more severe sleep disturbances, such as decreased slow wave sleep (SWS) and rapid eye movement (REM) and increased non-REM stages (N1 and N2). Comorbid conditions such as hypertension and diabetes mellitus were more common in these patients (P < 0.01 and P < 0.05, accordingly). Only the delayed recall scores were statistically lower in the moderate to severe OSA group than the primary snoring and mild OSA group (P < 0.05). The main factor associated with delayed recall was the ESS score rather than age or years of education among moderate-severe OSA patients ≤ 40 years of age (P < 0.05). After controlling for potential confounding factors such as age, gender, BMI, education, hypertension, diabetes, sleep stages (SWS and REM), minimum arterial oxygen saturation (min-SaO2), oxygen ODI, and AHI, there was a negative correlation between the Epworth Sleepiness Scale (ESS) score and the delayed recall scores. CONCLUSION: Patients with moderate to severe OSA had cognitive dysfunction, particularly impairment of delayed recall. Excessive daytime sleepiness (EDS) was significantly associated with cognitive dysfunction in young and middle-aged patients with OSA.

Childhood adversities and memory function in later life: the mediating role of activity participation.

BACKGROUND: Childhood adversities may lead to decreased activity participation in later life, impacting memory health in ageing adults. Childhood adversities related to deprivation and threat, as conceptualized by the Dimensional Model of Adversity, can exhibit distinct impacts on cognitive and emotional outcomes in children and younger adults. This study examined the potential influence of childhood deprivation and threat on memory function in later life and the mediating role of activity participation in these relationships. METHODS: This study used data from the first wave of Panel Study of Active Ageing and Society (PAAS), a representative survey of Hong Kong residents aged 50 or above (N = 1,005). Key variables included late-life memory function measured by delayed recall test, deprivation- and threat-related childhood adversities, and the frequency of participation in informal and formal types of activities. Mediation tests were used for analysis. RESULTS: Childhood deprivation was associated with a lower late-life memory function, whereas threat was not. The negative effects of childhood deprivation and its subdomain, economic hardship, on memory function were mediated by activity participation. Total participation scores presented the strongest mediating effect (17.3-20.6%), with formal activities playing a more substantial mediating role than informal activities in mitigating the effect of childhood deprivation. CONCLUSIONS: These findings expand the applicability of the Dimensional Model of Adversity to ageing populations, highlighting the influence of deprivation on life-long cognitive development. Furthermore, this study revealed an indirect mechanism by which childhood deprivation affects memory health in old age through diverse activity participation.

Cognitive performance trends among European older adults: exploring variations across cohorts, gender, and educational levels (2007-2017).

BACKGROUND: This study explores recent cohort trends in cognitive performance among older Europeans from 2007 to 2017, addressing three key questions: (1) Did cognitive performance improve universally and across the performance distribution during this period? (2) Did these improvements occur across educational levels and for both men and women? (3) Can established risk factors explain these performance gains? METHODS: Using data from the Survey of Health, Ageing and Retirement in Europe (SHARE) across 12 European countries, we assessed immediate recall, delayed recall, and verbal fluency in individuals aged 60 to 94 in both 2007 and 2017 (n = 32 773). Differences between the two time points were estimated with linear mixed effects regression models and quantile regression. RESULTS: Cognitive performance improved in all age groups, across educational levels, and for both men and women between 2007 and 2017. Notably, improvements were more pronounced at the upper end of the performance distribution for delayed recall and verbal fluency. Education explained approximately 20% of the observed improvements. Risk factors did not explain the observed improvements. CONCLUSIONS: European cohorts of both younger-old and older adults continue to exhibit improvements in cognitive performance. Variation in the size of the cohort improvements across the performance distributions in delayed recall and in verbal fluency may contribute to growing inequalities in cognitive outcomes. Future research should further investigate the potential heterogeneity in cognitive performance gains. TRIAL REGISTRATION: Not applicable.

Visuoconstructional Abilities of Patients With Subjective Cognitive Decline, Mild Cognitive Impairment and Alzheimer's Disease.

BACKGROUND: Via the Vienna Visuoconstructional Test 3.0 (VVT 3.0) delayed recall we combined the assessment of visuoconstructive abilities and memory and investigated the test's potential to support diagnostic processes, including staging and the elaboration of a cognitive profile. METHODS: We retrospectively analysed the data of 368 patients of the Department of Neurology, Medical University of Vienna, between 04/2014 and 10/2020 that had performed the VVT 3.0. Our sample involved 70 healthy controls (HC), 29 patients with subjective cognitive decline (SCD), 154 patients with mild cognitive impairment (MCI) and 115 patients with Alzheimer's disease (AD). We investigated the differences in the VVT 3.0 scores, as well as the VVT's ability to differentiate between AD and nonAD by calculating receiver-operating-characteristic (ROC) curves, ideal cut-offs and a logistic regression model. RESULTS: Results stated that the VVT 3.0 delayed recall scores were able to differentiate between all diagnostic groups, respectively, except HC-SCD and SCD-MCI. The ROC analyses determined an AUC of 0.890, 95% CI [0.855; 0.925], P < .001, and the ideal cut-off at 29.5 points that maximised sensitivity at 0.896 and specificity at 0.81. The logistic regression model classified 83.4% of AD patients correctly and delivered a significant Cohen's Kappa of 0.619 (P < .001). CONCLUSION: As the VVT 3.0 revealed satisfactory values of diagnostic accuracy in our sample, it could enrich clinical diagnosing. However, for more clarity about its informative value in other populations, there remains a need for future studies with other samples.

Recurrent radiation recall dermatitis 40 years after radiation therapy for breast cancer.

Radiation recall dermatitis is an inflammatory reaction of the skin, which occurs at previously irradiated areas, usually following a subsequent exposure to an aggravating factor. Recall dermatitis can occur weeks to months after radiation, and the longest duration between radiation and dermatitis has been reported to be about 25 years. Here, we report a case of recurrent radiation recall dermatitis that developed spontaneously after 40 years following radiation for breast cancer. This case suggests that radiation recall dermatitis can occur much later than previously reported. In spite of this late presentation, topical anti-inflammatory agents managed the condition well.

Contrastive intonation effects on word recall for information-structural alternatives across the sexes.

Focus highlights the fact that contextual alternatives are relevant for the interpretation of an utterance. For example, if someone says: "The meeting is on TUESDAY," with focus marked by a pitch accent on "Tuesday," the speaker might want to correct the assumption that the meeting is on Monday (an alternative date). Intonation as one way to signal focus was manipulated in a delayed-recall paradigm. Recall of contextual alternatives was tested in a condition where a set of alternatives was evoked by contrastive intonation. A control condition used intonation contours reported for broad focus in German. It was hypothesized that contrastive intonation improves recall, just as focus-sensitive particles (e.g., 'only') do, compared to sentences without such particles. Participants listened to short texts introducing a list of three elements from taxonomic categories. One of the three elements was re-mentioned in a subsequent critical sentence, realized with either a broad (H+!H*) or with a contrastive intonation contour (L+H*). Cued recall of the list elements was tested block-wise. Results show that contrastive intonation enhances recall for focus alternatives. In addition, it was found that the observed recall benefit is predominantly driven by females. The results support the assumption that contextual alternatives are better encoded in memory irrespective of whether focus is expressed prosodically or by a focus-sensitive particle. The results further show that females are more sensitive to pragmatic information conveyed through prosody than males.

Differential effects of unipolar versus bipolar depression on episodic memory updating.

Episodic memories, when reactivated, can be modified or updated by new learning. Since such dynamic memory processes remain largely unexplored in psychiatric disorders, we examined the impact of depression on episodic memory updating. Unipolar and bipolar depression patients, and age/education matched controls, first learned a set of objects (List-1). Two days later, participants in all three groups were either reminded of the first learning session or not followed by the learning of a new set of objects (List-2). Forty-eight hours later, List-1 recall was impaired in unipolar and bipolar patients compared to control participants. Further, as expected, control participants who received a reminder spontaneously recalled items from List-2 during recall of List-1, indicative of an updated List-1 memory. Such spontaneous intrusions were also seen in the unipolar and bipolar patients that received the reminder, suggesting that memory updating was unaffected in these two patient groups despite impaired recall of List 1. Unexpectedly, we observed a trend towards higher intrusions, albeit statistically insignificant, not only in the reminder but also in the no-reminder subgroups of bipolar patients. We probed this further in a second cohort by testing recall of List-2, which was also impaired in both depression groups. Again bipolar patients showed intrusions, but this time in the reverse order from List-1 into List-2, independent of a reminder. Taken together, despite impaired recall, updating of episodic memories was intact and unidirectional in unipolar depression. In contrast, indiscriminate updating, as evidenced by bidirectional interference between episodic memories, was seen in bipolar depression. These findings reveal a novel distinction between unipolar versus bipolar depression using a reactivation-dependent memory updating paradigm.

Association between delayed recall and T2* relaxation time of the subiculum in adolescents: Implications for ultra-high-field magnetic resonance imaging.

AIM: The aim of this study was to assess neuropsychological correlations with the T2* relaxation time (T2*-RT) of hippocampal subregions in adolescents using ultra-high-field (UHF) 7.0-T magnetic resonance imaging (MRI). METHODS: We assessed the T2*-RT of hippocampal subregions in 31 healthy 11th- or 12th-grade high school students using an UHF 7.0-T MRI system. T2*-RT of the cornu ammonis (CA) 1, CA2, CA3, and CA4 subregions and the subiculum were calculated for both the left and right hippocampus. Seven subtests of the Cambridge Neuropsychological Test Automated Battery were administered to the subjects to assess visuospatial memory. RESULTS: Poor performances in delayed recall in the pattern-recognition test were significantly correlated with longer T2*-RT in the bilateral subiculum (right, r = -0.480, P = 0.006; left, r = -0.648, P < 0.001) and the left CA2 (r = -0.480, P = 0.006). CONCLUSION: This study showed that longer T2*-RT in the subiculum were associated with poorer performances in delayed recall in the visual memory tasks. This finding suggests that the subiculum might play a predominant role in delayed recall in adolescents.

Comparing the neuropsychological profiles of mild dementia with Lewy bodies and mild Alzheimer's disease.

BACKGROUND: The present study was conducted to detect neuropsychological differences and to identify discriminators between mild dementia with L ewy bodies (DLB ) and mild A lzheimer's disease (AD ). METHODS: The present study included 37 mild DLB patients, 48 mild AD patients, and 80 healthy elderly individuals. A comprehensive battery of neuropsychological tests was administrated to assess their cognitive function. Linear stepwise discriminant analysis was used to identify the neuropsychological measures with values that could differentiate between mild DLB and mild AD . RESULTS: The mild DLB group had greater impairments in attention, executive function, and visuospatial ability, while mild AD patients performed significantly worse on memory tests. Linear stepwise discriminant analysis indicated that the M emory and E xecutive S creening's 5-min delayed recall test was the best neuropsychological discriminator between mild DLB and mild AD . CONCLUSIONS: Different patterns of cognitive impairment facilitate the differentiation of mild DLB from mild AD . For patients with mild dementia, better performance on the M emory and E xecutive S creening's 5-min delayed recall test suggests that the diagnosis is more likely DLB than AD .

[The Amsterdam Dementia Screening Test in cognitively healthy and clinical samples. An update of normative data]. / De Amsterdamse Dementie-Screeningstest (ADS) bij ouderen zonder neurocognitieve stoornis. Implicaties voor de klinische praktijk.

The six tests in the Amsterdam Dementia Screening Test (ADST) examine the cognitive domains of episodic memory (delayed picture recognition, word learning), orientation, category fluency (animals and occupations), constructional ability (figure copying) and executive function (alternating sequences). New normative data were collected in a sample of 102 elderly volunteers (aged 65-94), including subjects with medical or other health conditions, except dementia or frank cognitive impairment (MMSE > 24). Included subjects were independent in complex instrumental activities of daily living.Fluency, not the other tests, needed adjustment for age and education. A deficit score (0-1) was computed for each test. Summation (range 0-6) proved useful in differentiating patients with dementia (N = 741) from normal elderly (N = 102).Positive and negative predictive power across a range of summed deficit scores and base rates are displayed in Bayesian probability tables.In the normal elderly, delayed recall for eight words was tested and adjusted for initial recall. A recognition test mixed the target words with eight distractors. Delayed recognition was adjusted for immediate and delayed recall.The ADST and the normative data in this paper help the clinical neuropsychologist to make decisions concerning the presence or absence of neurocognitive disorder in individual elderly examinees.

Subject-specific functional parcellation via prior based eigenanatomy.

We present a new framework for prior-constrained sparse decomposition of matrices derived from the neuroimaging data and apply this method to functional network analysis of a clinically relevant population. Matrix decomposition methods are powerful dimensionality reduction tools that have found widespread use in neuroimaging. However, the unconstrained nature of these totally data-driven techniques makes it difficult to interpret the results in a domain where network-specific hypotheses may exist. We propose a novel approach, Prior Based Eigenanatomy (p-Eigen), which seeks to identify a data-driven matrix decomposition but at the same time constrains the individual components by spatial anatomical priors (probabilistic ROIs). We formulate our novel solution in terms of prior-constrained ℓ1 penalized (sparse) principal component analysis. p-Eigen starts with a common functional parcellation for all the subjects and refines it with subject-specific information. This enables modeling of the inter-subject variability in the functional parcel boundaries and allows us to construct subject-specific networks with reduced sensitivity to ROI placement. We show that while still maintaining correspondence across subjects, p-Eigen extracts biologically-relevant and patient-specific functional parcels that facilitate hypothesis-driven network analysis. We construct default mode network (DMN) connectivity graphs using p-Eigen refined ROIs and use them in a classification paradigm. Our results show that the functional connectivity graphs derived from p-Eigen significantly aid classification of mild cognitive impairment (MCI) as well as the prediction of scores in a Delayed Recall memory task when compared to graph metrics derived from 1) standard registration-based seed ROI definitions, 2) totally data-driven ROIs, 3) a model based on standard demographics plus hippocampal volume as covariates, and 4) Ward Clustering based data-driven ROIs. In summary, p-Eigen incarnates a new class of prior-constrained dimensionality reduction tools that may improve our understanding of the relationship between MCI and functional connectivity.

Learning sung lyrics aids retention in normal ageing and Alzheimer's disease.

Previous studies have suggested that presenting to-be-memorised lyrics in a singing mode, instead of a speaking mode, may facilitate learning and retention in normal adults. In this study, seven healthy older adults and eight participants with mild Alzheimer's disease (AD) learned and memorised lyrics that were either sung or spoken. We measured the percentage of words recalled from these lyrics immediately and after 10 minutes. Moreover, in AD participants, we tested the effect of successive learning episodes for one spoken and one sung excerpt, as well as long-term retention after a four week delay. Sung conditions did not influence lyrics recall in immediate recall but increased delayed recall for both groups. In AD, learning slopes for sung and spoken lyrics did not show a significant difference across successive learning episodes. However, sung lyrics showed a slight advantage over spoken ones after a four week delay. These results suggest that singing may increase the load of initial learning but improve long-term retention of newly acquired verbal information. We further propose some recommendations on how to maximise these effects and make them relevant for therapeutic applications.

The amyloid beta 42/38 ratio as a plasma biomarker of early memory deficits in cognitively unimpaired older adults.

The amyloid beta (Aß) 42/40 ratio has been widely studied as a biomarker in Alzheimer's disease (AD); however, other Aß peptides could also represent relevant biomarkers. We measured levels of Aß38/40/42 in plasma samples from cognitively-unimpaired older adults and determined the relationships between Aß levels and amyloid positron-emission-tomography (PET) and performance on a learning and memory task. We found that all Aß peptides individually and the Aß42/40 ratio, but not the Aß42/38 ratio, were significantly correlated with brain amyloid (Aß-PET). Multiple linear modeling, adjusting for age, sex, education, APOE4 and Aß-PET showed significant associations between the Aß42/38 ratio and memory. Further, associations between the Aß42/38 ratio and learning scores were stronger in males and in Aß-PET-negative individuals. In contrast, no significant associations were detected between the Aß42/40 ratio and any learning measure. These studies implicate the Aß42/38 ratio as a biomarker to assess early memory deficits and underscore the utility of the Aß38 fragment as an important biomarker in the AD field.

Multi-omics and pathway analyses of genome-wide associations implicate regulation and immunity in verbal declarative memory performance.

BACKGROUND: Uncovering the functional relevance underlying verbal declarative memory (VDM) genome-wide association study (GWAS) results may facilitate the development of interventions to reduce age-related memory decline and dementia. METHODS: We performed multi-omics and pathway enrichment analyses of paragraph (PAR-dr) and word list (WL-dr) delayed recall GWAS from 29,076 older non-demented individuals of European descent. We assessed the relationship between single-variant associations and expression quantitative trait loci (eQTLs) in 44 tissues and methylation quantitative trait loci (meQTLs) in the hippocampus. We determined the relationship between gene associations and transcript levels in 53 tissues, annotation as immune genes, and regulation by transcription factors (TFs) and microRNAs. To identify significant pathways, gene set enrichment was tested in each cohort and meta-analyzed across cohorts. Analyses of differential expression in brain tissues were conducted for pathway component genes. RESULTS: The single-variant associations of VDM showed significant linkage disequilibrium (LD) with eQTLs across all tissues and meQTLs within the hippocampus. Stronger WL-dr gene associations correlated with reduced expression in four brain tissues, including the hippocampus. More robust PAR-dr and/or WL-dr gene associations were intricately linked with immunity and were influenced by 31 TFs and 2 microRNAs. Six pathways, including type I diabetes, exhibited significant associations with both PAR-dr and WL-dr. These pathways included fifteen MHC genes intricately linked to VDM performance, showing diverse expression patterns based on cognitive status in brain tissues. CONCLUSIONS: VDM genetic associations influence expression regulation via eQTLs and meQTLs. The involvement of TFs, microRNAs, MHC genes, and immune-related pathways contributes to VDM performance in older individuals.

Association between plasma long-chain polyunsaturated n-3 fatty acids concentrations and cognitive function: findings from NHANES III.

Background: With increased life expectancy, cognitive decline has emerged as a prevalent neurodegenerative disorder. Objective: This study aimed to examine the correlation between concentrations of Plasma long-chain n-3 polyunsaturated fatty acids (LCPUFAs) and cognitive performance in elderly Americans. Methods: Data were analyzed from older adults enrolled in two NHANES cycles. Participants completed four cognitive assessments, including the Immediate Recall Test (IRT), Delayed Recall Test (DRT), Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST). Linear regression and restricted cubic spline modeling examined associations between plasma LCPUFAs levels and cognitive test outcomes. Results: The cohort included 610 adults aged 69 years on average, 300 (49.2%) males and 310 (50.8%) females. The median LCPUFAs concentration was 309.4 µmol/L, with an interquartile range of 244.7-418.9 µmol/L. In unadjusted and adjusted generalized linear regression model analyses, circulating LCPUFAs exhibited significant positive correlations with DRT performance. No relationships were detected among those with chronic conditions (chronic heart failure, stroke, diabetes). A significant association between LCPUFAs levels and DRT scores was evident in males but not females. Conclusion: Plasma LCPUFAs concentrations were significantly associated with DRT performance in males free of chronic illnesses, including heart failure, stroke, and diabetes.

Exploring the relationship between marital quality and cognitive function: A systematic review.

Cognitive function is an important indicator of healthy aging as it is central to maintaining functional independence, performing job-related tasks, decision-making, and improving quality of life. Therefore, researchers seek to identify biopsychosocial factors that can help preserve cognitive function in aging individuals. One such factor is the maintenance of good quality marital relationships. Research has consistently shown that married individuals fare better in terms of both physical and psychological health compared to their unmarried counterparts. However, being married is not universally beneficial - the quality of a marriage is also important to consider. To explore the issue further, we conducted a systematic review to examine the association between marital quality and cognitive function. PubMed, PsycINFO, and Scopus were searched for eligible articles examining any measure of marital quality and any cognitive outcome from the inception of each database to January 9th, 2024. Following two levels of citation screening by two independent reviewers, we included 15 articles representing 11 unique studies. Data were synthesized narratively following the Synthesis without Meta-Analysis guidelines and a risk of bias assessment was conducted using the Joanna Briggs Institute checklist. Most articles had a low risk of bias. Although some findings suggested more positive marital quality was associated with improved cognitive function, the results were not uniformly positive; some results were inverse or null, depending upon factors such as differences in study designs and measures of marital quality or cognition. This review is the first attempt to synthesize the literature on this topic. Our findings highlight that any examination of marital status and cognition should also consider contextual factors such as marital quality.

Episodic memory dysfunction and hypersynchrony in brain functional networks in cognitively intact subjects and MCI: a study of 379 individuals.

Delayed recall (DR) impairment is one of the most significant predictive factors in defining the progression to Alzheimer's disease (AD). Changes in brain functional connectivity (FC) could accompany this decline in the DR performance even in a resting state condition from the preclinical stages to the diagnosis of AD itself, so the characterization of the relationship between the two phenomena has attracted increasing interest. Another aspect to contemplate is the potential moderator role of the APOE genotype in this association, considering the evidence about their implication for the disease. 379 subjects (118 mild cognitive impairment (MCI) and 261 cognitively intact (CI) individuals) underwent an extensive evaluation, including MEG recording. Applying cluster-based permutation test, we identified a cluster of differences in FC and studied which connections drove such an effect in DR. The moderation effect of APOE genotype between FC results and delayed recall was evaluated too. Higher FC in beta band in the right occipital region is associated with lower DR scores in both groups. A significant anteroposterior link emerged in the seed-based analysis with higher values in MCI. Moreover, APOE genotype appeared as a moderator between beta FC and DR performance only in the CI group. An increased beta FC in the anteroposterior brain region appears to be associated with lower memory performance in MCI. This finding could help discriminate the pattern of the progression of healthy aging to MCI and the relation between resting state and memory performance.

Verbal memory formation across PET-based Braak stages of tau accumulation in Alzheimer's disease.

A classical early sign of typical Alzheimer's disease is memory decline, which has been linked to the aggregation of tau in the medial temporal lobe. Verbal delayed free recall and recognition tests have consistently probed useful to detect early memory decline, and there is substantial debate on how performance, particularly in recognition tests, is differentially affected through health and disease in older adults. Using in vivo PET-Braak staging, we investigated delayed recall and recognition memory dysfunction across the Alzheimer's disease spectrum. Our cross-sectional study included 144 cognitively unimpaired elderly, 39 amyloid-ß+ individuals with mild cognitive impairment and 29 amyloid-ß+ Alzheimer's disease patients from the Translational Biomarkers in Aging and Dementia cohort, who underwent [18F]MK6240 tau and [18F]AZD4694 amyloid PET imaging, structural MRI and memory assessments. We applied non-parametric comparisons, correlation analyses, regression models and voxel-wise analyses. In comparison with PET-Braak Stage 0, we found that reduced, but not clinically significant, delayed recall starts at PET-Braak Stage II (adjusted P < 0.0015), and that recognition (adjusted P = 0.011) displayed a significant decline starting at PET-Braak Stage IV. While performance in both delayed recall and recognition related to tau in nearly the same cortical areas, further analyses showed that delayed recall rendered stronger associations in areas of early tau accumulation, whereas recognition displayed stronger correlations in mostly posterior neocortical regions. Our results support the notion that delayed recall and recognition deficits are predominantly associated with tau load in allocortical and neocortical areas, respectively. Overall, delayed recall seems to be more dependent on the integrity of anterior medial temporal lobe structures, while recognition appears to be more affected by tau accumulation in cortices beyond medial temporal regions.

Mapping the long-term delayed recall-based cortex-hippocampus network constrained by the structural and functional connectome: a case-control multimodal MRI study.

BACKGROUND: Connectome mapping may reveal new treatment targets for patients with neurological and psychiatric diseases. However, the long-term delayed recall based-network with structural and functional connectome is still largely unknown. Our objectives were to (1) identify the long-term delayed recall-based cortex-hippocampus network with structural and functional connectome and (2) investigate its relationships with various cognitive functions, age, and activities of daily living. METHODS: This case-control study enrolled 131 subjects (73 amnestic mild cognitive impairment [aMCI] patients and 58 age- and education-matched healthy controls [HCs]). All subjects completed a neuropsychological battery, activities of daily living assessment, and multimodal magnetic resonance imaging. Nodes of the cortical-hippocampal network related to long-term delayed recall were identified by probabilistic fiber tracking and functional connectivity (FC) analysis. Then, the main and interaction effects of the network on cognitive functions were assessed by a generalized linear model. Finally, the moderating effects of the network on the relationships between long-term delayed recall and clinical features were analyzed by multiple regression and Hayes' bootstrap method. All the effects of cortex-hippocampus network were analyzed at the connectivity and network levels. RESULTS: The result of a generalized linear model showed that the bilateral hippocampus, left dorsolateral superior frontal gyrus, right supplementary motor area, left lingual gyrus, left superior occipital gyrus, left superior parietal gyrus, left precuneus, and right temporal pole (superior temporal gyrus) are the left and right cortex-hippocampus network nodes related to long-term delayed recall (P < 0.05). Significant interaction effects were found between the Auditory Verbal Learning Test Part 5 (AVLT 5) scores and global properties of the left cortex-hippocampus network [hierarchy, clustering coefficient, characteristic path length, global efficiency, local efficiency, Sigma and synchronization (P < 0.05 Bonferroni corrected)]. Significant interaction effects were found between the general cognitive function/executive function/language and global properties of the left cortex-hippocampus network [Sigma and synchronization (P < 0.05 Bonferroni corrected)]. CONCLUSION: This study introduces a novel symptom-based network and describes relationships among cognitive functions, brain function, and age. The cortex-hippocampus network constrained by the structural and functional connectome is closely related to long-term delayed recall.