Delayed Recall Memory Research Articles

Relationship Between Cognitive Performance, Physical Activity, and Socio-Demographic/Individual Characteristics Among Aging Americans.

Physical activity (PA) has emerged as a promising approach to delay Alzheimer's disease and related dementias, but the optimal intensity of PA to improve cognitive health remains unknown. To evaluate the association between duration and intensity of PA and cognitive domains (executive function, processing speed, and memory) in aging Americans. Linear regressions in hierarchical blocks for variable adjustment and the size of effect (η2) were analyzed by using the data of 2,377 adults (age = 69.3±6.7 years) from the NHANES 2011-2014. Participants with 3-6 h/week of vigorous- and > 1 h/week of moderate-intensity PA scored significantly higher in executive function and processing speed domains of cognition compared to inactive peers (η2 = 0.005 & 0.007 respectively, p < 0.05). After adjustment, the beneficial effects of 1-3 h /week of vigorous-intensity PA became trivial for delayed recall memory domain test scores (β= 0.33; 95% CI: -0.01,0.67; η2 = 0.002; p = 0.56). There was no linear dose-response relationship between the cognitive test scores and weekly moderate-intensity of PA. Interestingly, higher handgrip strength and higher late-life body mass index were associated with a higher performance across all cognitive domains. Our study supports habitual PA with superior cognition health in some but not all domains among older adults. Furthermore, increased muscle strength and higher late-life adiposity may also impact cognition.

Evaluating depressive symptoms, BDNF Val66Met, and APOE-ε4 as moderators of response to computerized cognitive training in heart failure

BackgroundDepressive symptoms, brain-derived neurotrophic factor (BDNF) Val66Met, and apolipoprotein (APOE)-ε4 may moderate response to computerized cognitive training (CCT) interventions among patients with heart failure (HF). ObjectivesThe purpose of this study was to examine moderators of intervention response to CCT over 8 months among patients with HF enrolled in a 3-arm randomized controlled trial. Outcomes were memory, serum BDNF, working memory, instrumental activities of daily living (IADLs), and health-related quality of life (HRQL). Methods256 patients with HF were randomized to CCT, computerized crossword puzzles active control, and usual care control groups for 8 weeks. Data were collected at enrollment, baseline, 10 weeks, and 4 and 8 months. Mixed effects models were computed to evaluate moderators. ResultsAs previously reported, there were no statistically significant group by time effects in outcomes among the 3 groups over 8 months. Tests of moderation indicated that depressive symptoms and presence of BDNF Val66Met and APOE-ε4 were not statistically significant moderators of intervention response in outcomes of delayed recall memory, serum BDNF, working memory, IADLs, and HRQL. In post hoc analysis evaluating baseline global cognitive function, gender, age, and HF severity as moderators, no significant effects were found. HF severity was imbalanced among groups (P = .049) which may have influenced results. ConclusionsStudies are needed to elucidate biological mechanisms of cognitive dysfunction in HF and test novel interventions to improve memory, serum BDNF, working memory, IADLs and HRQL. Patients may need to be stratified or randomized by HF severity within intervention trials.

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

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. 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). 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 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. 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.

Subtle Differences in Cognition in 70-Year-Olds with Elevated Cerebrospinal Fluid Neurofilament Light and Neurogranin: A H70 Cross-Sectional Study.

Most research on cerebrospinal fluid (CSF) neurofilament light protein (NfL) as a marker for neurodegeneration and neurogranin (Ng) for synaptic dysfunction has largely focused on clinical cohorts rather than population-based samples. We hypothesized that increased CSF levels of NfL and Ng are associated with subtle cognitive deficits in cognitively unimpaired (CU) older adults. The sample was derived from the Gothenburg H70 Birth Cohort Studies and comprised 258 CU 70-year-olds, with a Clinical Dementia Rating score of zero. All participants underwent extensive cognitive testing. CSF levels of NfL and Ng, as well as amyloid β1-42, total tau, and phosphorylated tau, were measured. Participants with high CSF NfL performed worse in one memory-based test (Immediate recall, p = 0.013) and a language test (FAS, p = 0.016). Individuals with high CSF Ng performed worse on the memory-based test Supra Span (p = 0.035). When stratified according to CSF tau and Aβ42 concentrations, participants with high NfL and increased tau performed worse on a memory test than participants normal tau concentrations (Delayed recall, p = 0.003). In participants with high NfL, those with pathologic Aβ42 concentrations performed worse on the Delayed recall memory (p = 0.044). In the high Ng group, participants with pathological Aβ42 concentrations had lower MMSE scores (p = 0.027). However, in regression analysis we found no linear correlations between CSF NfL or CSF Ng in relation to cognitive tests when controlled for important co-variates. Markers of neurodegeneration and synaptic pathology might be associated with subtle signs of cognitive decline in a population-based sample of 70-year-olds.

Floor and ceiling effects on the Montreal Cognitive Assessment in patients with Parkinson's disease in Brazil.

To explore the floor and ceiling effects on the MoCA in patients with PD in Brazil. Cross-sectional study with data from patients with PD from five Brazilian Movement Disorders Clinics, excluding individuals with a possible diagnosis of dementia. We analyzed the total score of the MoCA, as well as its seven cognitive domains. The floor and ceiling effects were evaluated for the total MoCA score and domains. Multivariate analyses were performed to detect factors associated with floor and ceiling effects. We evaluated data from 366 patients with PD and approximately 19% of individuals had less than five years of education. For the total MoCA score, there was no floor or ceiling effect. There was a floor effect in the abstraction and delayed memory recall domains in 20% of our sample. The ceiling effect was demonstrated in all domains (80.8% more common in naming and 89% orientation), except delayed recall. Education was the main factor associated with the floor and ceiling effects, independent of region, sex, age at evaluation, and disease duration. The floor and ceiling effects are present in specific domains of the MoCA in Brazil, with a strong impact on education. Further adaptations of the MoCA structure for underrepresented populations may reduce these negative effects.

Positive Affect and Cognitive Functioning in Older African American Adults

AbstractBackgroundPrevious research has demonstrated a link between affect and cognitive functioning, particularly showing that negative affect is related to lower cognitive performance across several cognitive domains. However, the relationship between positive affect (PA) and cognitive functioning is not as thoroughly characterized, though some previous work suggests that PA may be related to improved memory consolidation and greater cognitive flexibility. There is little research, if any, on the relation between PA and cognition in older adults from diverse racial backgrounds, who are also at greater risk for Alzheimer’s disease. PA may be a modifiable factor and target for intervention to deter cognitive decline. Therefore, we investigated whether PA was related to cognitive functioning in a sample of community‐dwelling, older African American adults. We predicted that greater PA would be associated with greater global cognitive functioning, immediate memory recall, and delayed memory recall while controlling for age.MethodTelephone screenings were administered to 194 older African Americans (aged 64‐94 years). Global cognitive functioning, immediate recall, and delayed recall were measured via the Telephone Interview for Cognitive Status‐Modified (TICSm). Immediate and delayed recall scores were excluded from global cognitive functioning scores to reduce conceptual overlap. PA was measured with a questionnaire of emotional functioning. We used hierarchical linear regression to determine whether PA was positively associated with cognitive functioning while controlling for age.ResultHigher PA was predictive of greater global cognitive functioning, after accounting for the effect of age (F(2,191) = 15.70, p&lt;.001; ΔR2 = .05, b = 0.68, SE = 0.21, p = .002). Similarly, higher PA was predictive of greater immediate recall (F(2,191) = 14.10, p&lt;.001; ΔR2 = .03, b = 0.45, SE = 0.19, p = .019) and delayed recall (F(2,191) = 7.44, p&lt;.001; ΔR2 = .02, b = 0.48, SE = 0.23, p = .035).ConclusionIn support of our hypothesis, we have demonstrated that greater PA is associated with greater global cognitive functioning, immediate memory recall, and delayed memory recall among older African American adults. Past studies report some relationships between PA and cognition, though little, if any, work has been done with aging adults from diverse racial backgrounds. Understanding how PA relates to cognition in late life is crucial because it may be a modifiable protective factor and a target for intervention.

Night blood pressure variability, brain atrophy, and cognitive decline.

BackgroundAlthough blood pressure variability (BPV) has emerged as a novel risk factor for Alzheimer's disease, few studies have examined the effects of night BPV on brain structure and function. This study investigated the association of night BPV with brain atrophy and cognitive function changes.MethodsThe analysis included 1,398 participants with valid ambulatory blood pressure (BP) monitoring at baseline and both baseline and 4-year follow-up brain magnetic resonance images who were recruited from the Korean Genome and Epidemiology Study. Participants underwent a comprehensive neuropsychological test battery. BPV was derived from ambulatory BP monitoring and calculated as a standard deviation (SD) of 24-h and daytime and nighttime BP.ResultsDuring the median follow-up of 4.3 years, increased SD of night systolic or diastolic BP was an indicator of total brain volume reduction, while daytime BPV or night average BP was not associated with total brain volume changes. High SD of night systolic BP was associated with reduced gray matter (GM) volume, independent of average night BP, and use of antihypertensive drugs. It also was associated with a reduction of temporal GM volume, mostly driven by atrophy in the left entorhinal cortex and the right fusiform gyrus. In cognitive performance, high variability of night systolic BP was associated with a decrease in visual delayed recall memory and verbal fluency for the category.ConclusionIncreased night BPV, rather than night mean BP, was associated with reduced brain volume and cognitive decline. High night BPV could be an independent predictor for rapid brain aging in a middle-aged population.

Widespread ripples synchronize human cortical activity during sleep, waking, and memory recall

Declarative memory encoding, consolidation, and retrieval require the integration of elements encoded in widespread cortical locations. The mechanism whereby such "binding" of different components of mental events into unified representations occurs is unknown. The "binding-by-synchrony" theory proposes that distributed encoding areas are bound by synchronous oscillations enabling enhanced communication. However, evidence for such oscillations is sparse. Brief high-frequency oscillations ("ripples") occur in the hippocampus and cortex and help organize memory recall and consolidation. Here, using intracranial recordings in humans, we report that these ∼70-ms-duration, 90-Hz ripples often couple (within ±500 ms), co-occur (≥ 25-ms overlap), and, crucially, phase-lock (have consistent phase lags) between widely distributed focal cortical locations during both sleep and waking, even between hemispheres. Cortical ripple co-occurrence is facilitated through activation across multiple sites, and phase locking increases with more cortical sites corippling. Ripples in all cortical areas co-occur with hippocampal ripples but do not phase-lock with them, further suggesting that cortico-cortical synchrony is mediated by cortico-cortical connections. Ripple phase lags vary across sleep nights, consistent with participation in different networks. During waking, we show that hippocampo-cortical and cortico-cortical coripples increase preceding successful delayed memory recall, when binding between the cue and response is essential. Ripples increase and phase-modulate unit firing, and coripples increase high-frequency correlations between areas, suggesting synchronized unit spiking facilitating information exchange. co-occurrence, phase synchrony, and high-frequency correlation are maintained with little decrement over very long distances (25 cm). Hippocampo-cortico-cortical coripples appear to possess the essential properties necessary to support binding by synchrony during memory retrieval and perhaps generally in cognition.

Cogniphobia and neuropsychological functioning in migraine.

Cogniphobia refers to the fear and avoidance of cognitive exertion, believed to cause or exacerbate headache. The objective of the present study was to demonstrate associations between cogniphobia and key fear-avoidance constructs. In this cross-sectional study, 72 adults with migraine were recruited from a tertiary headache center. Patients completed the Cogniphobia Scale for Headache Disorders (CS-HD) and a series of self-reported surveys and neuropsychological measures that assessed patient demographics, migraine diagnosis and headache characteristics, current pain severity, emotional state (i.e., anxiety, pain-related fear, and depression), cognitive exertion, and functioning (self-reported disability, self-reported cognitive symptoms, and neuropsychological measures). The CS-HD was associated with greater anxiety (Patient-Reported Outcomes Measurement Information System; PROMIS Anxiety; r = 0.39, p = .001), pain-related fear (PASS-20; ρ = 0.37, p = .002), self-reported cognitive symptoms (ABS; ρ = 0.38, p = .001), self-reported headache disability (HDI; r = 0.28, p = .022), and depression (PROMIS Depression; r = 0.25, p = .039). The CS-HD was also associated with lower scores on neuropsychological measures of semantic fluency (Animal Naming; r = -0.29, p = .015), visual immediate recall memory (RCFT Immediate Recall; r = -0.27, p = .027), visual delayed recall memory (RCFT Delayed Recall; r = -0.36, p = .002), and visual recognition memory (RCFT Recognition; r = -0.42, p < .001), with comparable findings when adjusting for depression and anxiety. This study demonstrated associations between cogniphobia and key fear-avoidance constructs. Fear-avoidance constructs, such as cogniphobia, are important constructs to consider when evaluating migraine and neuropsychological functioning. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Distinct Effects of the Apolipoprotein E ε4 Genotype on Associations Between Delayed Recall Performance and Resting-State Electroencephalography Theta Power in Elderly People Without Dementia.

BackgroundAbnormal electroencephalography (EEG) activity has been demonstrated in mild cognitive impairment (MCI), and theta rhythm might be inversely related to memory. The apolipoprotein E (ApoE) epsilon 4 (ε4) allele, as a genetic vulnerability factor for pathologic and normal age-related cognitive decline, may influence different patterns of cognitive dysfunction. Therefore, the present study primarily aimed to verify the role of resting theta rhythm in delayed recall deficits, and further explore the effects of the ApoE genotype on the associations between the resting theta power and delayed recall performance in the elderly individuals without dementia.MethodsA total of 47 individuals without dementia, including 23 MCI and 24 healthy subjects (HCs), participated in the study. All subjects were administered the Hopkins Verbal Learning Test–Revised (HVLT-R) to measure delayed recall performance. Power spectra based on resting-state EEG data were used to examine brain oscillations. Linear regression was used to examine the relationships between EEG power and delayed recall performance in each subgroup.ResultsThe increased theta power in the bilateral central and temporal areas (Ps = 0.02–0.044, uncorrected) was found in the patients with MCI, and were negatively correlated with delayed recall performance (rs = −0.358 to −0.306, Ps = 0.014–0.036, FDR corrected) in the elderly individuals without dementia. The worse delayed recall performance was associated with higher theta power in the left central and temporal areas, especially in ApoE ε4 non-carriers and not in carriers (rs = −0.404 to −0.369, Ps = 0.02–0.035, uncorrected).ConclusionOur study suggests that theta disturbances might contribute to delayed recall memory decline. The ApoE genotype may have distinct effects on EEG-based neural correlates of episodic memory performance.

Vitamin B6, B9, and B12 Intakes and Cognitive Performance in Elders: National Health and Nutrition Examination Survey, 2011-2014.

PurposeThis research intended to investigate vitamin B6, B9, and B12 consumption in relation to the risk of low cognitive performance (LCP) among elderly adults.Patients and MethodsWe analyzed data of 2421 participants retrieved from the National Health and Nutrition Examination Survey (NHANES) 2011–2014 database in this cross-sectional study. Cognitive performance was evaluated by the Consortium to Establish a Registry for Alzheimer’s disease (CERAD) word learning and recall modules, the animal fluency test (AF), and the digit symbol substitution test (DSST). Participants who scored the lowest 25th percentile were categorized in the LCP group. The Dietary Interview-Total Nutrient Intakes dataset was used to determine the dietary intake of B vitamins in the participants. The low intake group and adequate intake group were differentiated based on the recommended dietary allowance. Subgroup analyses were conducted to assess the relations between 3 B vitamins and cognitive performance among different sex, race, and age groups.ResultsCompared with low vitamin B6 intake (<1.7 mg/day), adequate vitamin B6 intake (≥1.7 mg/day) corresponded to a 31.7% decrease in LCP odds in the DSST tests. Participants who consumed adequate B9 (≥400 mcg/day) were associated with 31.2%, 33.8%, and 46.5% declines in the risk of LCP in the CERAD, AF, and DSST tests in contrast to those having low B9 intake (<400 mcg/day). Adequate vitamin B12 intake (≥2.4 mcg/day) correlated with a lower LCP occurrence in the CERAD, AF, and DSST tests, with 30.5%, 21.5%, and 33.3% reductions, respectively. Further, the relations between 3 B vitamins and cognitive performance varied across different sex, race, and age groups of people.ConclusionAdequate dietary vitamin B9 and B12 intakes are significantly associated with a better cognitive performance in immediate and delayed memory recall, categorical verbal fluency, processing speed, sustained attention, and working memory among elders assessed in the CERAD, AF, and DSST tests.

Subtypes of social support availability are not differentially associated with memory: a cross-sectional analysis of the Comprehensive Cohort of the Canadian Longitudinal Study on Aging

ABSTRACT This study investigated the association between subtypes of social support availability (SSA) and memory in persons aged 45 to85 years (n = 24,719). We examined two memory outcomes using a modified Rey AuditoryVerbal Learning Test (RAVLT)–immediate recall (RAVLT I) and delayed recall(RAVLT II)–and five subtypes of SSA: affectionate, emotional/informational,positive interactions, tangible, overall. We found statistically significant andadjusted positive associations between all SSA subtypes and memory, except forpositive interactions and delayed recall memory. For RAVLT I, the regression coefficients (s) ranged from 0.03 to 0.07; the s for RAVLT II ranged from 0.02 to 0.05. The differences in s for each SSA subtype ( RAVLT I – RAVLT II) ranged from 0.00 to 0.02 (mean difference = 0.01; 95% confidence interval = −0.01 to 0.03). All effect sizes, regardless of SSA subtype or memory outcome, were small and clinically unimportant.

Gestures analysis during a picture description task: Capacity to discriminate between healthy controls, mild cognitive impairment, and Alzheimer's disease

The main objective of this study is to compare the gesticulation of the five study groups that conform the evolution from healthy ageing to a moderate stage of Alzheimer's disease (AD). As a secondary aim we intend to assess the capacity of co-speech gestures to discriminate between the two main groups of amnestic Mild Cognitive Impairment (MCI), executive MCI (ex-MCI) and temporo-medial MCI (tm-MCI), since this last group is the one with the highest rate of progression to AD. 52 participants were divided into five groups, according to their global cognition state (healthy controls, ex-MCI, tm-MCI, mild AD, and moderate AD). They were videotaped during a picture description task and their verbal (speech fluency and lexical diversity measures) and non-verbal communication (gestural production) performances were analysed. Statistical analysis confirmed that the global cognition performance was worse in patients with greater cognitive impairment, and MCI groups differ from each other in delayed recall memory. Concerning verbal communication, time of speech was lower in the healthy control group when compared with the rest of the groups. In the non-verbal communication aspect, a trend toward statistical significance was found in iconic gestures per minute, iconic gestures per word and iconic gestures for word substitution. Pairwise comparison highlighted these variables as potential differentiating factor between ex-MCI, tm-MCI and mild AD groups. As for the first objective, our study results demonstrated there was not a linear progression in gestural production among groups. In relation to the second objective, outcomes pointed to a great value, since iconic gestures variables have been identified as a potential marker for the specific identification of tm-MCI individuals, who are a subgroup of amnestic MCI with a greater predisposition to progress to Alzheimer's disease.

Brain Perfusion Abnormalities after Radiotherapy Measured by 3-Dimensional Arterial Spin Labeling MRI and Correlations with Cognitive Impairment.

The purpose of this study was to use a 3-dimensional arterial spin labeling (3D ASL) magnetic resonance (MR) method to measure cerebral blood flow (CBF) before and after radiotherapy, and correlate changes with time after receiving radiotherapy and cognitive function. Patients with nasopharyngeal carcinoma receiving radiotherapy at our institution were recruited for the study. Participants were divided into three groups: Pre-radiotherapy control (PC) group, acute reaction period (ARP) group, and delayed reaction period (DRP)group. Thirty-four patients were included in the study. Compared with the PC group, the ARP group exhibited significantly decreased perfusion in the left anterior cingulate cortex (ACC) and right putamen, and increased perfusion in the right cerebellum (Crus 1), right inferior occipital gyrus, left lingual gyrus, left precuneus, and left calcarine gyrus. in the DRP group, increased perfusion was noted in the right cerebellum (Crus 1) and decreased perfusion in the left superior frontal gyrus. CBF differences were observed in several brain areas in the DRP group as compared to the ARP group (P < 0.001). Total Montreal Cognitive Assessment score, and subdomain language and delayed memory recall scores were significantly lower in the ARP and DRP groups than in the PC group (P < 0.05). Data suggest that ASL allows for non-invasive detection of radiation-induced whole-brain CBF changes, which is transient, dynamic and complicated and may be a factor contributing to cognitive impairment induced by radiotherapy for nasopharyngeal carcinoma.

Physical Activity and Memory Function among Older Adults in Lebanon: Differences by Sex and Rural-Urban Living

Introduction: The increase in the population of 60 years and above has led to an increase in dementia. Middle East and North Africa region (MENA) has one of the highest prevalence of dementia. One of the factors revealing promising results in reducing the burden of dementia, yet not researched in MENA and in other parts of the world, is physical activity. Objective: We aimed to assess the association between subjective and objective physical activity, and memory recall of older adults with no dementia in Lebanon. We also investigated the moderating effect of sex and place of residence on this association. Methods: This is a secondary data analysis of a cross-sectional study conducted in 2013 on a community of 502 older adults 65 years of age and above, selected randomly from two areas, Lebanon’s capital, Beirut, and Mount Lebanon. After excluding those who had dementia diagnoses and who did not have data on physical activity, the eligible sample was 459 persons. Physical activity was assessed by three indicators: physical activity perception, walking half a kilometer, and 2-minute step test (2MST). Memory recall, defined as episodic memory, was measured using a 10-word list-learning test with two outcomes: immediate and delayed. Regression models were performed adjusting for cluster effect. Additionally, associations between main exposures and memory recall were stratified by sex and rural/urban residence at the univariate and multivariate levels. Results: The findings of this study revealed that the three measures of physical activity were significantly associated with higher memory function, at a significance level of 0.05. The data demonstrated that sex and place of residence did not modify the association between physical activity measures and immediate and delayed memory recall. Conclusion: Physical activity of older adults should be promoted for a variety of health reasons including improvement of memory recall. Further research is needed to determine the long-term impact on the relationship between physical activity and episodic memory.

Memory and executive function are associated with distinct patterns of regional cerebral perfusion in dementia‐free APOE‐ε4 carriers and non‐carriers

AbstractBackgroundThe primary genetic risk factor for Alzheimer’s disease is the apolipoprotein ε4 (APOE‐ε4) allele, which confers significant risk for early symptom onset and future dementia. Prior studies have examined links between memory function and medial temporal perfusion in APOE‐ε4 carriers and non‐carriers, but findings have been mixed regarding the direction of relationships. Additionally, prior work has not examined whether other cognitive domains, such as executive function, are similarly associated with functionally relevant regional perfusion (i.e., in frontal regions). The present study aimed to 1) clarify the relationship between medial temporal perfusion and memory performance and 2) examine novel links between executive function and frontal perfusion in APOE‐ε4 carriers and non‐carriers.MethodDementia‐free older adults recruited from the community were classified as APOE‐ε4 carriers (n=18) or non‐carriers (n=30) via genotype analysis. We used pseudocontinuous arterial spin labeling MRI to quantify cerebral perfusion in regions involved in memory (medial temporal) and executive function (medial frontal). Comprehensive neuropsychological testing assessed memory (Logical Memory I &amp; II; Visual Reproduction I &amp; II) and executive function (Stroop color‐word interference; Trail making tests A &amp; B, category fluency). Multiple linear regression, modeled separately within carriers and non‐carriers, examined associations between perfusion and cognition, with age, sex, and education as covariates.ResultWithin APOE‐ε4 carriers, medial temporal hypoperfusion was associated with worse immediate and delayed recall memory in verbal and visual paradigms. Similarly, frontal hypoperfusion was associated with worse verbal category fluency. In non‐carriers, relationships between medial temporal perfusion and memory were absent. Relationships between frontal perfusion and executive function were in the opposite direction as those observed in APOE‐ε4 carriers, with frontal hyperperfusion predicting worse Stroop color‐word, Trails A, and Trails B performance.ConclusionWe observed positive associations between regional perfusion and corresponding cognitive domains in APOE‐ε4 carriers, while relationships were absent or negative within non‐carriers. Our findings highlight the importance of examining preclinical cerebrovascular dysfunction in relation to cognition in individuals at risk for progression to dementia. Future longitudinal studies will be needed to further examine the value of perfusion, cognition, and APOE‐ε4 carrier status in predicting future decline.

Associations between the use of histamine‐2 receptor antagonists vs. proton pump inhibitors and cognitive decline: A stratified longitudinal study in people with and without cognitive impairment

AbstractBackgroundStudies suggest associations between proton pump inhibitors (PPI) and higher dementia risk compared with no use; however, several studies did not consider histamine‐2 receptor antagonists (H2RAs), the other common acid suppressant for similar indications. Comparisons between them are clinically relevant, both in older people with and without cognitive impairment due to Alzheimer’s disease (AD).MethodParticipants using a PPI or H2RA were selected from the National Alzheimer's Coordinating Center database from September 2005 to February 2021. Cox regressions were used to compare 5‐year conversion from normal cognition to mild cognitive impairment (MCI) or dementia, and 5‐year conversion from MCI to dementia, between PPI and H2RA users. In a propensity score matched sample of clinically diagnosed mild‐moderate AD, a linear mixed‐effects regression was used to assess PPI vs. H2RA use in rates of decline in global cognition (Clinical Dementia Rating [CDR®] Sum of Boxes; CDR‐SOB) up to 5 years. Delayed memory recall (Wechsler Memory Scale–Logical Memory test) was explored using a mixed‐effects negative binomial regression. Demographics, smoking, alcohol abuse, baseline CDR‐SOB, comorbidities, concurrent medications used, and apolipoprotein E genotype were included as covariates in Cox regressions or in propensity score.ResultCognitively normal H2RA (n=547, events=62) vs. PPI users (n=2237, events=312) did not differ in their risk for MCI or AD (Hazard Ratio; HR [95% Confidence Interval; CI] = 1.067 [0.807‐1.410]). In MCI, H2RA use (n=288, events=75) was associated with faster 5‐year dementia conversion (HR [95% CI] = 1.402 [1.085‐1.811]), compared with PPI use (n=1413, events=355). In AD, H2RA (n=212) vs. PPI (n=636) use was not associated with differential rates of decline in global cognition (B [95% CI] = ‐0.023 [‐0.324, 0.277] CDR‐SOB per year). However, H2RA use was associated with faster memory decline (Rate Ratio [95% CI] = 0.783 [0.671‐0.915]) in AD, but no associations with memory decline were found in MCI or normal cognition.ConclusionDifferential associations with cognitive decline were not observed in cognitively normal older people. Among people with MCI or AD, H2RA use was associated with faster rates of conversion to dementia, or memory decline, respectively. Anti‐cholinergic burden might explain the associations.

Plasma and cerebrospinal fluid neurofilament light protein concentrations are differentially associated with biomarker evidence of neurodegeneration in a community‐based population of 70‐year‐olds

AbstractBackgroundNeurofilament light protein (NfL) is the best‐established fluid biomarker for general neurodegeneration, predicting poor outcome in cognitive function across neurodegenerative dementias. Currently, there are few studies examining the correlation of plasma and cerebrospinal fluid (CSF) NfL with other fluid and imaging biomarkers for neurodegeneration.MethodThe sample (n= 287) was derived from the Gothenburg H70 Birth cohort 1944 study, conducted in 2014‐2016. CSF NfL, total‐Tau (t‐Tau), phospho‐Tau (p‐Tau), neurogranin, CSF/serum albumin ratio and plasma NfL were measured and brain magnetic resonance imaging (MRI) was conducted. Participants were examined with comprehensive neuropsychiatric and somatic examinations, and dementia was diagnosed according to DSM III criteria. In linear models adjusted for age and sex, NfL was examined in relation to other demographics, cognitive tests, CSF biomarkers and MRI measurements. Sub analysis were also performed on participants with or without β‐Amyloid pathology, defined as a CSF β‐Amyloid 42 ≤ 530 pg/mL.ResultNfL in plasma and CSF presented a moderate correlation (Spearman’s R=0.41, p&lt;0.001). P‐NfL was associated with worse delayed memory recall (p=0.019), smaller hippocampus volume (p=0.001), larger white matter lesion volume (p=0.004), as well as CSF levels of β‐amyloid 42 (p=0.043), β‐amyloid 42/40 (p=0.049), β‐amyloid 42/t‐Tau (p=0.007), CSF NfL (p&lt;0.001) and BMI (p&lt;0.001). CSF NfL was associated with t‐Tau (p=0.001), p‐Tau (p&lt;0.001), neurogranin (p=0.014), albumin ratio (Qalb) (p=0.001), P‐NfL (p&lt;0.001), and BMI (p=0.033). In participants with prevalent β‐amyloid 42 pathology, P‐NfL was associated with β‐amyloid 42 (p=0.009), β‐amyloid 42/40 (p=0.043), β‐amyloid 42/t‐Tau (p=0.010) and CSF NfL (p&lt;0.001). In participants without β‐amyloid 42 pathology, P‐NfL associated with BMI (p&lt;0.001), smaller hippocampus volume (p=0.007) and CSF NfL (p&lt;0.001).ConclusionAlthough CSF NfL and P‐NfL concentrations are correlated, the biomarker measured in the two sample types presents distinct associations with biomarker evidence of AD pathology and neurodegeneration. P‐NfL was associated with several markers that are characteristic of AD, whereas CSF NfL demonstrated more associations with synaptic and neurodegeneration.

Tau deposition and structural connectivity demonstrate differential association patterns with neurocognitive tests

Tau neurofibrillary tangles have a central role in the pathogenesis of Alzheimer’s Disease (AD). Mounting evidence indicates that the propagation of tau is assisted by brain connectivity with weakened white-matter integrity along the propagation pathways. Recent advances in tau positron emission tomography tracers and diffusion magnetic resonance imaging allow the visualization of tau pathology and white-matter connectivity of the brain in vivo. The current study aims to investigate how tau deposition and structural connectivity are associated with memory function in prodromal AD. In this study, tau accumulation and structural connectivity data from 83 individuals (57 cognitively normal participants and 26 participants with mild cognitive impairment) were associated with neurocognitive test scores. Statistical analyses were performed in 70 cortical/subcortical brain regions to determine: 1. the level of association between tau and network metrics extracted from structural connectivity and 2. the association patterns of brain memory function with tau accumulation and network metrics. The results showed that tau accumulation and network metrics were correlated in early tau deposition regions. Furthermore, tau accumulation was associated with worse performance in almost all neurocognitive tests performance evaluated in the study. In comparison, decreased network connectivity was associated with declines in the delayed memory recall in Craft Stories and Benson Figure Copy. Interaction analysis indicates that tau deposition and dysconnectivity have a synergistic effect on the delayed Benson Figure Recall. Overall, our findings indicate that both tau deposition and structural dysconnectivity are associated with neurocognitive dysfunction. They also suggest that tau-PET may have better sensitivity to neurocognitive performance than diffusion MRI-derived measures of white-matter connectivity.

Brazilian Version of Addenbrooke's Cognitive Examination-Revised in the Differential Diagnosis of Alzheimer'S Disease and Behavioral Variant Frontotemporal Dementia.

Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) are frequent causes of dementia and, therefore, instruments for differential diagnosis between these two conditions are of great relevance. To investigate the diagnostic accuracy of Addenbrooke's Cognitive Examination-Revised (ACE-R) for differentiating AD from bvFTD in a Brazilian sample. The ACE-R was administered to 102 patients who had been diagnosed with mild dementia due to probable AD, 37 with mild bvFTD and 161 cognitively healthy controls, matched according to age and education. Additionally, all subjects were assessed using the Mattis Dementia Rating Scale and the Neuropsychiatric Inventory. The performance of patients and controls was compared by using univariate analysis, and ROC curves were calculated to investigate the accuracy of ACE-R for differentiating AD from bvFTD and for differentiating AD and bvFTD from controls. The verbal fluency plus language to orientation plus name and address delayed recall memory (VLOM) ratio was also calculated. The optimum cutoff scores for ACE-R were <80 for AD, <79 for bvFTD, and <80 for dementia (AD + bvFTD), with area under the receiver operating characteristic curves (ROC) (AUC) >0.85. For the differential diagnosis between AD and bvFTD, a VLOM ratio of 3.05 showed an AUC of 0.816 (Cohen's d = 1.151; p < .001), with 86.5% sensitivity, 71.4% specificity, 72.7% positive predictive value, and 85.7% negative predictive value. The Brazilian ACE-R achieved a good diagnostic accuracy for differentiating AD from bvFTD patients and for differentiating AD and bvFTD from the controls in the present sample.