Changes In Episodic Memory Research Articles

The Impact of Episodic Memory on Decision-Making in Aging: Scenarios from Everyday Life Situations.

Background: Decision-making is a highly complex process that depends on numerous cognitive functions, such as episodic memory. It is also influenced by aging. However, how changes in episodic memory with age contribute to changes in decision-making is not clear yet. Objective: This work aimed to examine the role of two memory processes, recollection and familiarity, in decision-making in ageing. Method: Thirty young adults and 30 older adults performed two episodic memory tasks: recognition, which allowed for the measurement of recollection and familiarity, and recall, which allowed for the measurement of recollection. In both tasks, they first viewed a series of pictures and then were asked to recognise or recall them respectively. They also performed an original scenario task based on situations inspired by everyday life, evaluating decision-making under conditions of either risk or ambiguity. In this task, participants were presented with short descriptions of situations requiring a decision and had to choose between two given options. Results: Lower performances was observed in recall and recognition tasks in older than in young adults. In the scenarios task, young adults sought significantly more risk and ambiguity than older adults. In both young and older adults, recollection and familiarity processes were involved differently in decision-making. The former is more involved in decision-making under ambiguity, and the latter in decision-making under risk. Conclusions: The results suggest that decision-making changes with age, but that the involvement of the episodic memory, familiarity and recollection processes, does not appear to vary with age.

The Relationship Between 10-Year Changes in Cognitive Control Beliefs and Cognitive Performance in Middle and Later Adulthood.

The present study used a cross-lagged panel design with longitudinal data to test if there is a reciprocal relationship between cognitive control beliefs and cognition (e.g., executive functioning and episodic memory) over 10-years, whether frequency of engaging in stimulating cognitive activities mediated this relationship, and if these relationships varied by age. Data were collected as part of the second (M2, 2004-05) and third (M3, 2013-14) waves of the Midlife in the United States Study (MIDUS). The analysis sample included 2,532 participants with all variables at M2 and M3. Participants' ages ranged from 33 to 83 (M=54.92, SD=11.13) at M2. There was a reciprocal relationship between cognitive control beliefs and executive functioning. Higher executive functioning was related to greater maintenance of cognitive control beliefs for older, not younger, adults. Higher cognitive control beliefs were related to less decline in executive functioning. Though cognitive control beliefs predicted 10-year changes in episodic memory, the inverse relationship was not supported. Frequency of engaging in stimulating cognitive activities mediated the relationship between executive functioning and 10-year changes in cognitive control beliefs, but not cognitive control beliefs and 10-year changes in cognition. Cognitive control beliefs are a promising mechanism to help protect against age-related declines in both executive functioning and episodic memory. Moreover, executive functioning also impacts cognitive control beliefs. Specifically, those with higher executive functioning engage more frequently in stimulating cognitive activities, which helps maintain higher cognitive control beliefs.

Reducing age differences in the retrieval of verbatim and gist representations: Encoding manipulations.

Aging causes changes in episodic memory. While the ability to remember the general idea or gist of past episodes is relatively preserved from the effects of aging, the ability to remember the verbatim details of these episodes declines. The aim of the present study was to examine whether age-related differences in the quality of episodic representations could be reduced by manipulations of information encoding. Two experiments were conducted with younger adults (NExp.1 = 32, NExp.2 = 31, 18-27 years old) and older adults (NExp.1 = 31, NExp.2 = 30, 54-81 years old) in which either the retrieval of gist representations of studied items was facilitated by presenting items that could be grouped within the same category (Exp. 1) or the retrieval of verbatim details of studied items was facilitated by presenting the same items repeatedly (Exp. 2). Both manipulations proved effective in increasing retrieval of either gist or verbatim representations in a recognition task in younger and older adults. Increasing gist retrieval improved correct recognition performance for both younger and older adults but also led the latter to make more recognition errors. Increasing verbatim retrieval improved correct recognition performance for both younger and older adults, and the gain was greater for older adults. These findings support the notion that age-related changes in episodic memory can be explained by changes in the specificity of representations and suggest that simple encoding manipulations could improve episodic memory in older adults.

Examining the bidirectional longitudinal associations between body mass index and episodic memory following bariatric surgery

BackgroundThe relationship between obesity and episodic memory (i.e., conscious memory for specific events) is hypothesized to be bidirectional. Indeed, studies have shown that metabolic and bariatric surgery (MBS) is associated with episodic memory improvement, and better memory is associated with better postsurgical weight-loss outcomes. However, direct tests of the hypothesized bidirectional association between episodic memory and body mass index (BMI) in MBS are lacking, as few studies have employed repeated, prospective assessments of memory in conjunction with bidirectional modeling techniques. ObjectivesThe present study used latent change score analysis to examine the bidirectional longitudinal associations between episodic memory and BMI in the 2 years following MBS. SettingUniversity hospital; public practice. MethodsEpisodic memory function and BMI were assessed in adults prior to MBS, and at 1, 6, 12, 18, and 24-months postsurgery. ResultsA total of 124 participants (41% lost at 2-year follow-up) showed, on average, favorable weight-loss and episodic memory outcomes following MBS. Crucially, presurgery episodic memory predicted initial change in BMI at 1-month postsurgery, and postsurgery episodic memory at 1- and 6-months predicted change in BMI at 6- and 12-months postsurgery. No evidence was found for pre- and postsurgery BMI predicting changes in episodic memory. ConclusionsResults supported a unidirectional prospective relationship between episodic memory and weight change following MBS, such that better memory pre- and postsurgery predicted improved weight-loss outcomes. These findings highlight the likely importance of episodic memory function for weight change and support the potential benefit of targeting memory processes to improve weight-loss outcomes.

Correlates of Theta and Gamma Activity during Visuospatial Incidental/Intentional Encoding and Retrieval Indicate Differences in Processing in Young and Elderly Healthy Participants.

Incidental visuospatial learning acquired under incidental conditions is more vulnerable to aging than in the intentional case. The theta and gamma correlates of the coding and retrieval of episodic memory change during aging. Based on the vulnerability of incidental coding to aging, different theta and gamma correlates could occur under the incidental versus intentional coding and retrieval of visuospatial information. Theta and gamma EEG was recorded from the frontotemporal regions, and incidental/intentional visuospatial learning was evaluated in young (25-60 years old) and elderly (60-85 years old) participants. The EEG recorded during encoding and retrieval was compared between incidental low-demand, incidental high-demand, and intentional conditions through an ANCOVA considering the patient's gender, IQ, and years of schooling as covariates. Older adults exhibited worse performances, especially in place-object associations. After the intentional study, older participants showed a further increase in false-positive errors. Higher power at the theta and gamma bands was observed for frontotemporal derivations in older participants for both encoding and retrieval. Under retrieval, only young participants had lower power in terms of errors compared with correct responses. In conclusion, the different patterns of power and coherence support incidental and intentional visuospatial encoding and retrieval in young and elderly individuals. The correlates of power with behavior are sensitive to age and performance.

Identifying the nature of episodic memory deficits in Major Depressive Disorder using a Real-World What-Where-When task

ABSTRACT Deficits in episodic memory have been reported in various psychiatric conditions, including Major Depressive Disorder (MDD). Many widely used episodic memory tests do not have the ability to distinguish between impaired memory of separate components of a real-life event (e.g., what happened, where it happened and when), and impaired binding of such real-life features. To address this issue, a naturalistic, real-world What-Where-When memory task was employed to assess the nature of episodic memory impairments in MDD. A validation study established that the task is sensitive to age-related episodic memory changes, and that intentional encoding does not invalidate the task. The main study then compared the performance of patients with depression and control participants on the intentionally encoded WWW task. Patients with MDD presented an overall episodic memory impairment arising from deficits in object memory and the ability to bind objects to temporal context. Taken together, our study confirms the episodic memory impairment in MDD, by providing evidence of deficient object memory and reduced ability to bind temporal context to objects in patients. Our naturalistic WWW task presents a promising approach for thorough identification of the nature of episodic memory impairments, under a real-world environment, in various conditions, including MDD.

Association of estimated pulse wave velocity with cognitive function in a multiethnic diverse population: The Northern Manhattan Study.

Arterial stiffness is linked to age-related cognitive dysfunction. Estimated pulse wave velocity (ePWV) is associated with cerebrovascular disease. We sought to determine whether ePWV was associated with cognition in a multiethnic population. We included 1257 participants enrolled in a Northern Manhattan Study magnetic resonance imaging MRI-cognitive study (mean age 64±8 years, 61% women, 67% Hispanic, 18% non-Hispanic Black, 15% non-Hispanic white) and analyzed cognitive performance at two time points, at enrollment and on an average 5.0±0.6 years later. ePWV was calculated using baseline age and blood pressure. Cognition and cognitive change scores were regressed on ePWV in multivariable linear regression models. In adjusted models, ePWV (mean 11±2m/s) was significantly associated with cognition (b=-0.100, 95% CI, -0.120, -0.080) and cognitive change over time (b=-0.063, 95% CI, -0.082, -0.045). Effect modification by race and sex was found. In this multiethnic population, the associations of ePWV with cognitive performance underline the role of vascular stiffness in age-related cognitive decline. ePWV is a modest but independent predictor of cognitive function and cognitive decline among older individuals. After adjustment, the ePWV measure was inversely associated with performance and decline in global cognition, processing speed, episodic memory, executive function, and semantic memory. After adjustment, modification of the association between ePWV and change in episodic memory and executive function by race and ethnicity was suggested by a significant interaction term. The association between ePWV and episodic memory decline was stronger in females.

BDNF Val66Met moderates episodic memory decline and tau biomarker increases in early sporadic Alzheimer's disease.

Allelic variation in the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism has been shown to moderate rates of cognitive decline in preclinical sporadic Alzheimer's disease (AD; i.e., Aβ + older adults), and pre-symptomatic autosomal dominant Alzheimer's disease (ADAD). In ADAD, Met66 was also associated with greater increases in CSF levels of total-tau (t-tau) and phosphorylated tau (p-tau181). This study sought to determine the extent to which BDNF Val66Met is associated with changes in episodic memory and CSF t-tau and p-tau181 in Aβ + older adults in early-stage sporadic AD. Aβ + Met66 carriers (n = 94) and Val66 homozygotes (n = 192) enrolled in the Alzheimer's Disease Neuroimaging Initiative who did not meet criteria for AD dementia, and with at least one follow-up neuropsychological and CSF assessment, were included. A series of linear mixed models were conducted to investigate changes in each outcome over an average of 2.8years, covarying for CSF Aβ42, APOE ε4 status, sex, age, baseline diagnosis, and years of education. Aβ + Met66 carriers demonstrated significantly faster memory decline (d = 0.33) and significantly greater increases in CSF t-tau (d = 0.30) and p-tau181 (d = 0.29) compared to Val66 homozygotes, despite showing equivalent changes in CSF Aβ42. These findings suggest that reduced neurotrophic support, which is associated with Met66 carriage, may increase vulnerability to Aβ-related tau hyperphosphorylation, neuronal dysfunction, and cognitive decline even prior to the emergence of dementia. Additionally, these findings highlight the need for neuropsychological and clinicopathological models of AD to account for neurotrophic factors and the genes which moderate their expression.

Increased frequency of light physical activity during midlife and old age buffers against cognitive declines

Although it is well established that moderate-to-vigorous physical activity (MVPA) buffers against declines in cognitive health, less is known about the benefits of light physical activity (LPA). Research on the role of LPA is crucial to advancing behavioral interventions to improve late life health outcomes, including cognitive functioning, because this form of physical activity remains more feasible and amenable to change in old age. Our study examined the extent to which increases in LPA frequency protected against longitudinal declines in cognitive functioning and whether such a relationship becomes pronounced in old age when opportunities for MVPA are typically reduced. We analyzed 9-year data from the national Midlife in the United States Study (n = 2,229; Mage = 56 years, range = 33–83; 56% female) using autoregressive models that assessed whether change in LPA frequency predicted corresponding changes in episodic memory and executive functioning in middle and later adulthood. Increases in LPA frequency predicted less decline in episodic memory (β = 0.06, p = .004) and executive functioning (β = 0.14, p < .001) over the 9-year follow-up period, even when controlling for moderate and vigorous physical activity. Effect sizes for moderate and vigorous physical activity were less than half that observed for LPA. Moderation models showed that, for episodic memory, the benefits of increases in LPA frequency were more pronounced at older ages. Findings suggest that increases in LPA over extended periods of time may help slow age-related cognitive declines, particularly in later life when opportunities for MVPA are often diminished.

Bilingualism reduces associations between cognition and the brain at baseline, but does not show evidence of cognitive reserve over time

Abstract Studies suggest that bilingualism may be associated with better cognition, but the role of active bilingualism, the daily use of two languages, on cognitive trajectories remains unclear. One hypothesis is that frequent language switching may protect cognitive trajectories against effects of brain atrophy. Here, we examined interaction effects between language and brain variables on cognition among Hispanic participants at baseline (N = 153) and longitudinally (N = 84). Linguistic measures included self-reported active Spanish–English bilingualism or Spanish monolingualism. Brain measures included, at baseline, regions of gray matter (GM) thickness strongly correlated with cross-sectional episodic memory and executive function and longitudinally, tissue atrophy rates correlated with episodic memory and executive function change. Active Spanish–English bilinguals showed reduced association strength between cognition and gray matter thickness cross-sectionally, β=0.303, p &lt; .01 but not longitudinally, β=0.024, p = 0.105. Thus, active bilingualism may support episodic memory and executive function despite GM atrophy cross-sectionally, but not longitudinally.

Prediction of cognitive impairment using higher order item response theory and machine learning models.

Timely detection of cognitive impairment (CI) is critical for the wellbeing of elderly individuals. The MyCog assessment employs two validated iPad-based measures from the NIH Toolbox® for Assessment of Neurological and Behavioral Function (NIH Toolbox). These measures assess pivotal cognitive domains: Picture Sequence Memory (PSM) for episodic memory and Dimensional Change Card Sort Test (DCCS) for cognitive flexibility. The study involved 86 patients and explored diverse machine learning models to enhance CI prediction. This encompassed traditional classifiers and neural-network-based methods. After 100 bootstrap replications, the Random Forest model stood out, delivering compelling results: precision at 0.803, recall at 0.758, accuracy at 0.902, F1 at 0.742, and specificity at 0.951. Notably, the model incorporated a composite score derived from a 2-parameter higher order item response theory (HOIRT) model that integrated DCCS and PSM assessments. The study's pivotal finding underscores the inadequacy of relying solely on a fixed composite score cutoff point. Instead, it advocates for machine learning models that incorporate HOIRT-derived scores and encompass relevant features such as age. Such an approach promises more effective predictive models for CI, thus advancing early detection and intervention among the elderly.

Does the Impact of Episodic Memory Declines on Future Changes in Perceived Control Vary Based on Individuals' Experience With Cognitively Demanding Jobs?

This study proposes and evaluates a scenario wherein cognitive demands experienced at work can amplify the positive cross-lagged association of a shift in control beliefs following changes in episodic memory. From the Health and Retirement Study (2006-2018) for 9,998 participants aged 50 or above, we used repeated observations of memory and control beliefs, assessed with the Telephone Interview for Cognitive Status-modified (TICS-m) and self-mastery and perceived constraints questionnaires. A dual-Latent Change Score Model estimated the cross-lagged effects between memory and control beliefs, separately for individuals with prior high cognitive job demands and those without. A decline in memory led to decreased control beliefs in terms of perceived constraints, only among those with experiences in cognitively demanding jobs. High cognitive job demands may lead to a more cognitively oriented awareness of aging, thus amplifying the impact of memory decline on control constraints.

Effect of multivitamin-mineral supplementation versus placebo on cognitive function: results from the clinic subcohort of the COcoa Supplement and Multivitamin Outcomes Study (COSMOS) randomized clinical trial and meta-analysis of 3 cognitive studies within COSMOS

BackgroundLonger effects of multivitamin-mineral (MVM) supplementation on late-life cognitive function remain untested using in-person, detailed neuropsychological assessments. Furthermore, insufficient evidence exists for healthcare providers to recommend daily MVM supplements to prevent cognitive decline. ObjectivesThis study aimed to test MVM effects on cognitive change using in-person, detailed neuropsychological assessments and conduct a meta-analysis within COSMOS (COcoa Supplement and Multivitamin Outcomes Study) cognitive substudies for a robust evaluation of MVM effects on cognition. MethodsCOSMOS is a 2 × 2 factorial trial of cocoa extract (500 mg flavanols/d) and/or a daily MVM supplement for cardiovascular disease and cancer prevention among 21,442 United States adults aged ≥60 y. There were 573 participants in the clinic subcohort of COSMOS (that is, COSMOS-Clinic) who completed all cognitive tests administered at baseline. For the meta-analysis, we included nonoverlapping participants across 3 COSMOS cognitive substudies: COSMOS-Clinic (n = 573); COSMOS-Mind (n = 2158); COSMOS-Web (n = 2472). ResultsIn COSMOS-Clinic, we observed a modest benefit of MVM compared with placebo on global cognition over 2 y {mean difference [95% confidence interval (CI)] = 0.06 SD units (SU) (−0.003, 0.13)}, with a significantly more favorable change in episodic memory [mean difference (95% CI) = 0.12 SU (0.002, 0.23)] but not in executive function or attention [mean difference (95% CI) = 0.04 SU (−0.04, 0.11)]. The meta-analysis of COSMOS substudies showed clear evidence of MVM benefits on global cognition [mean difference (95% CI) = 0.07 SU (0.03, 0.11); P = 0.0009] and episodic memory [mean difference (95% CI) = 0.06 SU (0.03, 0.10); P = 0.0007]; the magnitude of effect on global cognition was equivalent to reducing cognitive aging by 2 y. ConclusionsIn COSMOS-Clinic, daily MVM supplementation leads to a significantly more favorable 2-y change in episodic memory. The meta-analysis within COSMOS cognitive substudies indicates that daily MVM significantly benefits both global cognition and episodic memory. These findings within the COSMOS trial support the benefits of a daily MVM in preventing cognitive decline among older adults.This trial was registered at COSMOS—clinicaltrials.gov as NCT02422745, at COSMOS-Mind—clinicaltrials.gov as NCT03035201, and at COSMOS-Web—clinicaltrials.gov as NCT04582617.

DOES INCREASING LIGHT PHYSICAL ACTIVITY IN MIDLIFE AND OLD AGE BUFFER AGAINST COGNITIVE DECLINES?

Abstract Although it is well established that moderate-to-vigorous physical activity (MVPA) buffers against cognitive declines, less is known about the benefits of lower intensity physical activities that are more feasible, inclusive, and amenable to change in old age. Our study examined the extent to which increases in light physical activity protected against longitudinal declines in cognitive functioning and whether such a relationship become pronounced in old age when opportunities for MVPA are often reduced. We analyzed 9-year data from the national Midlife in the United States Study (n=2,229; age=56±11.13 years) using regression models that assessed whether change in light physical activity predicted corresponding changes in episodic memory and executive functioning for adults across the lifespan. All models controlled for age, sex, socioeconomic status, functional status, and moderate and vigorous physical activity. Beyond more vigorous forms of physical activity, increasing light physical activity predicted less decline in episodic memory (β=.06, p=.010) and executive functioning (β=.15, p&amp;lt;.001) over the 9-year follow-up period. Effect sizes for moderate and vigorous physical activity on episodic memory (βs=.01-.02) and executive functioning (βs=.03) were less than half that observed for light physical activity. Moderation models showed that, for episodic memory, the benefits of increasing light physical activity were pronounced at older ages. Findings provide initial evidence that increasing light physical activity may help slow age-related declines in episodic memory and executive functioning and that its protective influence may become paramount in later life when individuals commonly encounter constraints that can limit their capacity to engage in MVPA.

MEDITERRANEAN DIET ADHERENCE PROSPECTIVELY PREDICTS NINE-YEAR CHANGES IN EPISODIC MEMORY

Abstract Mediterranean diet (MD) adherence has been shown to foster cognitive function during aging. Methods for measuring adherence to the MD typically provide or withhold points for foods consumed. Few investigations have examined how adherence to a Western adaptation of the MD may influence cognitive function over time in the United States. A modified MD that includes dairy products, whole grains, and plant-based proteins with limited consumption of sugar-sweetened beverages may be more attainable for many Americans than the traditional MD. This secondary analysis examined whether adherence to a modified MD was predictive of episodic memory and executive function over a 9-year study period. The second wave of the Midlife in the United States Study assessed general diet qualities with a food frequency questionnaire, and cognitive function was measured at both waves 2 and 3 (N = 816; age: 46 +/- 12 years; 56% female). Regression analyses were conducted to determine whether MD adherence predicted 9-year regressed change in cognitive function while controlling for age, sex, race, socioeconomic status (SES), and biomarkers of glucose homeostasis (hemoglobin a1c, insulin, and blood glucose). MD predicted changes in episodic memory (β = 0.075, p = 0.013) but not executive functioning (β = -0.028, p = 0.210). Exploratory moderator analyses suggested that MD associations with episodic memory were observed for only younger and middle-aged adults, females, White individuals, and persons with lower SES. Increased MD adherence may serve as a modifiable factor that supports cognitive function and preserved episodic memory during aging.

Effect of cocoa extract supplementation on cognitive function: results from the clinic subcohort of the COSMOS trial

BackgroundSome prior randomized clinical trials (RCTs) that tested the effects of cocoa extract (CE), a source of flavanols, on late-life cognition have yielded promising findings. A long-term RCT using in-person neuropsychological tests covering multiple cognitive domains may clarify the cognitive effects of CE. ObjectivesTo test whether daily supplementation with CE, compared with placebo, produces better cognitive change over 2 y. MethodsThe COcoa Supplement and Multivitamin Outcomes Study (COSMOS) is a 2 × 2 factorial RCT of CE [500 mg flavanols/d, including 80 mg (–)-epicatechin] and/or a daily multivitamin-mineral supplement for cardiovascular disease and cancer prevention among 21,442 United States adults aged ≥60 y. There were 573 participants in the clinic subcohort of COSMOS (that is, COSMOS-Clinic) who completed all cognitive tests at baseline; of these, 492 completed 2-y follow-up assessments. The primary outcome was global cognition (averaging z-scores across 11 tests). Secondary outcomes were episodic memory and executive function/attention. Repeated measures models were used to compare randomized groups. ResultsParticipants' mean age (standard deviation) was 69.6 (5.3); 49.2% were females. Daily supplementation with CE, compared with placebo, had no significant effect on 2-y change in global cognition {mean difference [95% confidence interval (CI)]: −0.01 (−0.08, 0.05) standard deviation units (SU)}. CE, compared with placebo, had no significant effects on 2-y change in episodic memory [mean difference (95% CI): −0.01 (−0.13, 0.10) SU] or executive function/attention [mean difference (95% CI): 0.003 (−0.07, 0.08) SU]. Subgroup analyses uncorrected for multiple-testing suggested cognitive benefits of CE supplementation, compared with placebo among those with poorer baseline diet quality. ConclusionsAmong 573 older adults who underwent repeat in-person, detailed neuropsychological assessments over 2 y, daily CE supplementation, compared with placebo, showed no overall benefits for global or domain-specific cognitive function. Possible cognitive benefits of CE among those with poorer diet quality warrant further study. Trial registrationThis trial was registered at clinicaltrials.gov with identifier – NCT02422745.

The effect of BDNF Val66Met on memory, CSF total‐tau, CSF ptau181 and CSF Aβ42 in early sporadic Alzheimer’s disease

AbstractBackgroundAllelic variation in the brain‐derived neurotrophic factor (BDNF) Val66Met polymorphism has been shown to moderate rates of cognitive decline in preclinical sporadic Alzheimer’s disease (i.e., Aβ+ older adults), and pre‐symptomatic dominantly inherited Alzheimer’s disease (DIAD). In DIAD, Met66 was also associated with greater increases in CSF levels of total‐tau and phosphorylated tau (p‐tau181). This study sought to determine the extent to which BDNF Val66Met is also associated with changes in episodic memory and CSF total‐tau and p‐tau181 in Aβ+ older adults in early‐stage sporadic AD.MethodAβ+ Met66 carriers (n = 94) and Val66 homozygotes (n = 192) enrolled in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) who did not meet criteria for AD dementia were included. Only participants with at least one follow‐up neuropsychological and CSF assessment were included. Episodic memory was measured by the ADNI Memory Composite and CSF samples were collected via lumbar puncture to determine levels of total‐tau, p‐tau181 and Aβ42. A series of linear mixed models were conducted to investigate changes in each outcome variable over 10 years, covarying for CSF Aβ42 (except when examining changes in CSF Aβ42), APOE ε4 status, sex, age, baseline diagnosis and years of education.ResultWhen followed over 10 years, Aβ+ Met66 carriers demonstrated significantly faster memory decline (d = 0.33) and significantly greater increases in CSF total‐tau (d = 0.30) and p‐tau181 (d = 0.29) compared to Val66 homozygotes, despite showing equivalent rates of change in CSF Aβ42 (Table 1; Figure 1).ConclusionIn non‐demented Aβ+ older adults, Met66 carriers showed greater memory decline and greater increases in both CSF total‐tau and CSF p‐tau181 over 10 years compared to Val66 homozygotes, despite showing equivalent changes in CSF Aβ42. This suggests that Met66 carriage, which is associated with lower BDNF availability and lower neurotrophic support, may confer greater vulnerability to Aβ‐related increases in tau compared to Val66 homozygosity in the early stages of sporadic AD.

Clinical Manifestations.

Alzheimer's disease (AD) is characterised biologically by beta-amyloid (Aβ) plaques and tau tangles, but autopsy studies reveal that most older adults also present with cerebrovascular disease (CVD) markers. Effects of biological AD on cognition in the context of concurrent CVD remain unclear. In older adults with CVD pathology, this study sought to determine ante-mortem cognitive trajectories associated with Aβ/tau positivity or negativity (+/-) at autopsy. Participants aged 65-95 classified as cognitively unimpaired at baseline from the National Alzheimer's Coordinating Center database, with ≥1 follow-up between 2005-2015, and available autopsy/APOE data were included (N = 924). Autopsy indicated that all participants had at least one of six CVD pathology markers. Participants were classified into four groups (A-T-, A+T-, A-T+, A+T+) based on semiquantitative Consortium to Establish a Registry for Alzheimer's Disease neuritic plaque staging and Braak staging. Linear mixed models including group × time interactions assessed rate of change in Preclinical Alzheimer's Cognitive Composite scores, episodic memory, and executive function. Interactions between age, sex, APOE ε4 × time and the interval between death/the final study visit were included as covariates. A+T+ adults demonstrated significantly faster cognitive decline on all outcomes in the ∼10 years preceding death compared to A-T-, A+T-, and A-T+ adults (Table 1, Figure 1, d = 0.15 - 0.39). At final visit prior to death, a greater proportion of A+T+ adults (36%) received a dementia diagnosis compared to A-T+ (14%) or A+T- (15%) (p <.001). When analyses were restricted to exclude dementia diagnoses, significantly faster decline on all outcomes (p's <.001, d = 0.06 - 0.36) was similarly observed in A+T+ adults compared to A-T-, A+T- and A-T+ adults (Figure 2). Cognitive trajectories were equivalent between A-T- and A+T- for all outcomes (p's >.55). ln older adults with CVD pathology, A+T+ at autopsy was associated with greater cognitive decline over 10 years preceding death compared to A+T-, A-T+, and A-T- older adults. Faster cognitive decline in this group in the context of low final visit dementia diagnoses may suggest that post-mortem A+T+ is associated with a steep trajectory of cognitive decline ante-mortem, but that dementia progression is not inevitable.

Moderation effects of APOE‐ε4 on marine omega‐3 fatty acids and its relation to change in cognitive function among community‐dwelling older adults

AbstractBackgroundIn a recent trial, we observed no effect of omega‐3 fatty acids (omega‐3s) supplementation on cognitive decline. However, brain concentrations and metabolism of lipid molecules in response to omega‐3s may be regulated by apolipoprotein E (APOE)‐ε4 allele status. Further, while APOE‐ε4 is an established risk factor for Alzheimer disease, its association with cognitive decline is uncertain, especially in more diverse samples. The few randomized clinical trials (RCTs) addressing the moderation of effects of omega‐3s on cognitive decline by APOE‐ε4 have yielded inconsistent findings. Thus, we examined moderation by APOE‐ε4 on effects of omega‐3s vs. placebo for global and domain‐specific cognitive change over 2 years in a well‐characterized, diverse sample of older adults.MethodsVITamin D and OmegA‐3 TriaL (VITAL) is a 2×2 factorial RCT of vitamin D3 (2000 IU/day) and/or omega‐3s (1 g/day including 460 mg of eicosapentaenoic acid and 380 mg of docosahexaenoic acid) for cardiovascular disease and cancer prevention. We included 743 VITAL in‐clinic sub‐cohort participants who completed all cognitive tests at baseline and had APOE genotype data. The primary outcome was change in global cognition (averaging z‐scores of 9 tests) over 2 years; episodic memory and executive function/attention were examined separately. We used multiplicative interaction terms in general linear models of response profiles to examine moderation by APOE‐ε4 carrier status on effects of omega‐3s vs. placebo for cognitive change outcomes over 2 years.ResultsThe mean age (standard deviation) of participants was 67.1 (5.3) years; 50.6% were females; 13.5% were from racial and/or ethnic minority backgrounds; and 24.9% were APOE‐ε4 allele carriers. Over 2 years, compared with APOE‐ε4 non‐carriers, APOE‐ε4 carriers had faster declines in global cognition and episodic memory but not in executive function/attention; e.g., the mean difference in change (95% confidence interval) for episodic memory comparing APOE‐ε4 carriers vs. non‐carriers was ‐0.18 (‐0.33 to ‐0.03). There were no significant interactions between APOE‐ε4 carrier status and randomization status (omega‐3s vs. placebo) on change in global, episodic memory, or executive function/attention scores.ConclusionAPOE‐ε4 significantly predicted cognitive decline but did not modify the effect of omega‐3s on global and domain‐specific cognitive change over 2 years.

“How Do You Know Who You Are?”: Marjorie Prime on Envisioning Humanity Through the Faculty of AI-Powered Memory as Reconstructive Tissue

In reference to the theme of the issue devoted to literary extremities, Jordan Harrison’s play Marjorie Prime raises thought-provoking questions about the potential benefits and drawbacks of advanced AI technology by exploring the nature of memory, identity, and mortality, as well as the ethical implications of creating artificial intelligence that can mimic human behavior and emotions. This article argues that the play positions its AI character—a computerized hologram of Marjorie’s late husband Walter—at the intersection of two divergent perspectives on memory reactivation enhanced by AI-powered technology. While, on the one hand, the humanoid is seen as a potent tool which helps to reduce the cognitive impairment caused by dementia, on the other hand, there is a concern that technological interventions may trigger episodic memory change, testifying to the plastic, and thus reconstructive, character of this foundational human faculty. The article seeks to negotiate the interplay of benefits and dangers of technology-assisted memory reactivation by exploring two divergent ideas represented by Marjorie’s daughter Tess and her son-in-law Jon regarding what would comfort their mother, and, ultimately, their differing ways of comforting each other and themselves individually as the carers of an elderly person. In analyzing how creative and destructive forces exhibited by AI-powered digital tools cross-inhabit the declining memory inflicted by dementia, the article unpacks both the vast potential and the limits of technology while attempting to answer uncomfortable questions about the essence of human existence posed by aging and dementia.