Selective Reminding Test Research Articles

Cognitive Decline Associated with Longitudinal Changes in 24‐h Ambulatory Blood Pressure Variability

AbstractBackgroundCognitive decline has been associated with variability in blood pressure (BP). However, whether the increment of the BP variability during follow‐up precedes cognitive decline remains undocumented. We aimed this study to investigate cognitive decline in relation to longitudinal changes in 24‐h reading‐to‐reading BP variability.MethodsWe conducted an observational longitudinal study that included 717 dementia‐free participants from the Maracaibo Aging Study who underwent follow‐up assessment in both 24‐h ambulatory BP monitoring and cognitive tests between 1998 and 2015. Cognitive domains consisted of selective reminding tests (total, long‐term, short‐term, and recognition memory) and the Mini‐Mental State Examination (MMSE). Cognitive decline was a longitudinal decrease in cognitive scores. Participants underwent 24‐h ambulatory BP monitoring between 2‐4 times – with at least one‐year interval. Systolic and diastolic BP variability was studied during 24‐h and divided into daytime (from 06h00 to 23h00), and nighttime (23h00 to 06h00) periods. To account for BP level, we used variability independent of the mean (VIM) to compute systolic and diastolic BP variability. Other measures of BP variability included the nocturnal BP drop in comparison to the daytime BP level, which was estimated as the night‐to‐day ratio. Statistics included multivariate linear regression mixed models.ResultsOverall, the mean age was 65.6±7.36 years old and 66.5% (n = 447) of the participants were women. In mixed models, a decline in all memory domains was associated with greater variability in the 24‐h, daytime, and nighttime systolic BP during follow‐up, with an estimated decline in cognitive scores ranging from ‐0.2 to ‐0.04 points per unit increase in VIM systolic BP during follow‐up (P values ranged from 0.022 to 0.003). Decline in total, short‐term, and MMSE memory domains was associated with greater 24‐h and daytime diastolic BP variability (P≤0.015). A lower night‐to‐day dipping ratio during follow‐up increased the risk of cognitive decline, with a ‐5.8 to ‐1.6 decline in long‐term memory and MMSE scores; respectively (P≤0.037).ConclusionsCognitive decline associates with greater reading‐to‐reading 24‐h BP variability and lower falls in nocturnal BP over time. These findings might be indicative of deteriorated regulatory mechanisms to maintain steady BP levels as individuals age.

Relationships between excessive daytime sleepiness and arterial stiffness with cognitive function in a racially diverse high‐risk cohort

AbstractBackgroundAs pathologic processes leading to Alzheimer’s disease (AD) begin many years before clinical diagnosis, assessment of pre‐clinical AD risk factors in high‐risk individuals is needed. Excessive daytime sleepiness (EDS) is associated with increased cardiovascular dysfunction, neuroinflammation, and neurodegeneration, leading to cognitive impairment. We tested the hypothesis that EDS and increased arterial stiffness are related to worse cognitive function in a cohort of Black or African American (B/AA) and non‐Hispanic White (NHW) participants.MethodA community‐based racially diverse sample of cognitively unimpaired adults (47‐83 years), most (87%) with a family history of AD, were enrolled. Cognitive testing took one hour and included domains of executive function, working memory, and verbal and visuospatial ability and language. Daytime sleepiness was measured with Epworth Sleepiness Scale (ESS); EDS was defined as ESS≥10. Arterial stiffness was measured using pulse wave velocity (PWV).ResultParticipants (N = 85) were 64±8 years of age, 75% female, 48% B/AA, and highly educated (81% ≥college). Mean central blood pressures were 126±18 mmHg (systolic) and 80±10 mmHg (diastolic), with no differences by race or sex. Scores were lower among B/AA versus NHW participants for Judgement of Line of Orientation (17.71±6.0 versus 23.53±6.0, p<.001, Cohen’s d = .083) and Multilingual Naming Test (28.25±2.7 versus 30.57±2.0, p = .005, d = .950). EDS was present among 15% of participants and associated with lower scores on Digit Symbol (p = .004, d = .917), and Multilingual Naming Test (p = .006, d = 1.455). Total time on Trails A was higher among those with EDS (36s versus 30s, p = .040, d = .575). Higher PWV values were associated with lower scores on Digit Symbol Substitution (r = ‐.259, p = .029), Buschke Selective Reminding Test (‐.298, p = .012), CERAD Word List (‐.306, p = .009), F‐A‐S (r = ‐.253, p = .033), and Animal Fluency (r = ‐.326, p = .006).ConclusionIn a racially diverse cohort at risk for AD, we found that excessive self‐reported daytime sleepiness and increased arterial stiffness were associated with worse scores across multiple cognitive domains. Poor sleep and vascular dysfunction are known contributors to AD pathology, providing potential modifiable targets of intervention to reduce or delay the development of AD in cognitively normal, but high‐risk individuals. Further work is needed for a better understanding of modifiable AD risk factors in diverse populations

Validation of the free and cued selective reminding test in Moroccan patients with mild cognitive impairment or Alzheimer's disease

Validation of the free and cued selective reminding test in Moroccan patients with mild cognitive impairment or Alzheimer's disease

Tracking the progression of Alzheimer's disease: Insights from metabolic patterns of SOMI stages

BackgroundSOMI (Stages of Objective Memory Impairment) is a novel classification that identifies six stages of memory decline in Alzheimer's Disease (AD) using the Free and Cued Selective Reminding Test (FCSRT). However, the relationship between SOMI stages and brain metabolism remains unexplored. This study aims to investigate the metabolic correlates of SOMI stages using FDG-PET in Mild Cognitive Impairment due to AD (MCI-AD) and early AD patients. MethodsOne hundred twenty-nine-patients (99 aMCI-AD and 30 AD), and 42 healthy controls (HCs) (MMSE = 29.2 ± .8; age:69.1 ± 8.6 years; education:10.7 ± 3.8 years) who underwent an extensive neuropsychological battery including FCSRT and brain FDG-PET were enrolled. According to their clinical relevance and available sample sizes, SOMI-4 (N = 24 subjects; MMSE score:26.6 ± 2.6: age:75.4 ± 3.2; education:9.9 ± 4.5) and SOMI-5 groups (N = 97; MMSE:25.3 ± 2.6; age:73.9 ± 5.8; education:9.4 ± 4.1) were investigated. ResultsCompared to HCs, SOMI-4 showed hypometabolism in the precuneus, medial temporal gyrus bilaterally, right pecuneus and angular gyrus. SOMI-5 exhibited broader hypometabolism, extending to the left posterior cingulate and medial frontal gyrus bilaterally. The conjunction analysis revealed overlapping areas in the precuneus, medial temporal gyrus bilaterally, and in the right angular gyrus and cuneus. The disjunction analysis identified SOMI-5 specific hypometabolism encompassing left inferior temporal gyrus, uncus and parahippocampal gyrus, and medial frontal gyrus bilaterally (p < .001, p-value (FWE) < .05). DiscussionSOMI-4 relates to posterior hypometabolism, while SOMI-5 to more extensive hypometabolism further encompassing frontal cortices, suggesting SOMI as a biologically relevant classification system of memory decline. ConclusionMemory decline staged with SOMI is associated with hypometabolism spreading in amnesic MCI-AD/AD, suggesting its usefulness as a clinical marker of increasing neurodegeneration.

38 Language and memory outcome after frontal or temporal resection for epilepsy

Objective:The purpose of this investigation was to examine neuropsychological functioning after frontal (FL) or temporal lobectomy (ATL) in patients with localization related epilepsy. Few studies have compared cognitive changes following FL and ATL. Past research found improvement on measures of verbal and visual memory along with confrontation naming after FL (Busch et al., 2017). In contrast, a number of studies have reported verbal memory and naming decline in those undergoing left ATL. The current study examined post-operative cognitive changes in epilepsy patients who underwent either a left or right FL or ATL.Participants and Methods:Subjects include 430 patients (204 men, 225 women, 1 gender not specified), who underwent surgical resection; Right FL = 25, Left FL = 26, Right ATL = 211, Left ATL = 168. Patients had a mean FSIQ = 90, ages ranging from 18 to 71 (mean age = 37 years), right (n=359), left (n=50), or mixed (n=18) handedness, and education ranging from 3 to 22 years (mean = 12.9 years of education). Change from pre- to post FL and ATL was examined in the following domains: learning and memory [Long Term Storage for Selective Reminding Tests (SRT), Wechsler’s Memory Scale (WMS): Logical Memory Delayed Recall (LM) and Visual Reproduction Delayed Recall (VR)], and language [Boston Naming Test (BNT)].Results:A one-way ANOVA was used to examine changes in language and memory. Our findings revealed statistically significant differences between resection groups for LM, SRT, and BNT. There were significant declines (p&lt;.001) for left ATL when compared to right ATL for LM, SRT, and BNT. There were significant declines for left ATL, when compared to the gains in both left (p&lt;.001; p=.002) and right (p=.018; p=.008) FL for LM and BNT. Left ATL also had significant declines when compared to gains in SRT (p&lt;.001) for right FL. There were significant declines for left FL when compared to right ATL for SRT (p=.007). Lastly, there were significant gains for right FL when compared to left FL for SRT (p=.020).Conclusions:The pre- to post-surgical neuropsychological change in learning, memory, and language is understudied in frontal lobe epilepsy (FLE); although several investigators reported some learning and memory impairments in FLE at either pre- or post-surgical time points (Johnson-Markve et al., 2011; Incisa Della Rocchetta et al., 1993). The current study suggests that resections of the frontal lobes are associated with better outcomes for naming and verbal memory (LM) when compared to left ATLs. Interestingly, verbal list learning declined more in left than right FL and right ATL patients suggesting a possible language based executive functioning component to this memory measure. As expected, our study further supports that left ATLs are associated with material specific memory declines. This pattern was not seen for those undergoing a right ATL (i.e., nonverbal memory did not decline in patients with right ATL).

79 Brief Subjective Memory Screener Predicts Memory Dysfunction

Objective:Alzheimer’s disease (AD) is expected to affect over 7 million older Americans by 2025. Development of fast and inexpensive screening measures for routine screening is critical for identifying those suffering from the earliest stages of AD including Mild Cognitive Impairment (MCI) and Subjective Cognitive Decline (SCD). Here we assess the validity and utility of a brief, 5-item SCD screener and its associations with neuropsychological performance as compared to an existing objective cognitive screener, the Mini Mental Status Exam (MMSE).Participants and Methods:Development: A brief, 5-item SCD questionnaire was developed based on a more extensive 20-item version previously validated (Chapman et al. 2021). Participants: 27 cognitively diverse (MCI and cognitively normal) community dwelling older adults were recruited for this study. Mean age: 71.9 ± 7. Inclusion criteria include memory concerns. Exclusion criteria include no previous diagnoses of neurodegenerative diseases and/or major stroke. Administration: Participants completed a brief, 5-item SCD screener along with cognitive testing including the MMSE and a clinically validated list-learning test, the Selective Reminding Test (SRT). Statistical Methods: Spearman 2-tailed correlations were conducted to assess the relationship between the two screening measures, and their relationships to the SRT. Outcome measures on the SRT included total recall (max: 72) and delayed recall (max: 12). All cognitive measures were demographically adjusted with normative data.Results:The mean total for the SCD screener was 2.1 ±1.1, and the mean MMSE score was 29.2 ± 1.2. The SCD screener was associated with MMSE scores (r= -.39, p= .043), SRT Total Recall (r= -.43, p= .024) and Delayed Recall (r=-.42, p=.031) measures. MMSE scores did not associate with either SRT outcome (p&gt;.05).Conclusions:Results support the utility and validity of a brief subjective cognitive decline screener for identifying those who may be experiencing memory dysfunction. The brief SCD screener outperformed the MMSE, an existing and widely used objective screening measure. Associations between the SCD screener and SRT outcomes support the validity and utility of the brief screener and recapitulate previous findings with the more extensive version of the SCD questionnaire (Chapman et al. 2021). Ongoing research is focusing on the utility of the screener in frontline clinical settings and translation of the screener into Spanish.

91 Remote Smartphone-Based Assessment Predicts Standard Neuropsychological Test Performance and Cerebral Amyloid Status in Cognitively Normal Older Adults

Objective:Routine cognitive screening in the elderly may facilitate earlier diagnosis of neurodegenerative diseases and access to care and resources for patients and families. However, despite growing rates of Alzheimer's and related disorders (ADRD), the availability and implementation of cognitive screening for older adults in the US remains quite limited. Remote cognitive assessment via smartphone app may reduce several barriers to more widespread screening. We examined the validity of a remote app-based cognitive screening protocol in healthy older adults by examining remote task convergence with standard-person assessments and cerebral amyloid (Aß) status as an AD biomarker.Participants and Methods:Participants (N =117) were cognitively unimpaired adults aged 60-80 years (67.5% female, 88% White, 75% education &gt; 16 years). A portion had Aß PET imaging results available from prior research participation [(Aß positive (Aß+) n =26, and Aß negative (Aß-) n = 44]. A modified Telephone Interview for Cognitive Status (TICSm) cutoff score of &gt;34 was used to establish unimpaired cognition. Participants completed 8 consecutive assessment days using Mobile Monitoring of Cognitive Change (M2C2), a smartphone app-based testing platform developed as part of the National Institute of Aging's Mobile Toolbox initiative. Brief (i.e., 3-4 minute) M2C2 sessions were assigned daily within morning, afternoon, and evening time windows. Tasks included measures of visual working memory (WM), processing speed (PS), and episodic memory (EM) (see Thompson et al., 2022). Participants then completed a battery of standard neuropsychological assessments in-person at a follow-up visit.Results:Participants completed 22.6 (SD = 2.6) out of 24 assigned sessions (3 sessions x 8 days) on average. Performance on all M2C2 tasks decreased significantly with age. Women performed significantly better on WM and EM tasks relative to men. There were no detectable significant differences in performance by race or education. Shorter mean reaction time on M2C2 PS trials predicted faster Trails A and B completion (ß = .26, p &lt; .01, 95% CI [3.8, 23.3] and ß = .20, p &lt; .05, 95% CI [.23, 6.8], respectively). Greater mean M2C2 WM accuracy predicted longer maximum backward digital span (ß = .24, p = .01, 95% CI [.02, .16]). Greater mean M2C2 EM accuracy predicted stronger Logical Memory delayed recall (ß = .33, p &lt; .001, 95% CI [.004, .012]) and total immediate recall on the Free and Cued Selective Reminding Test (ß = .19, p &lt; .05, 95% CI [.000, .006]). Moreover, EM significantly distinguished Aß- and Aß+ individuals (t (68) = 3.0, p &lt; .01) with fair accuracy (AUC = .72).Conclusions:Mean performance across 8-days on each M2C2 task predicted same-domain cognitive task performance on a standard assessment battery, with medium effect sizes. Performance on the EM task was also sensitive to cerebral Aß status, consistent with subtle memory changes implicated in the preclinical stage of AD. These findings support the validity of this remote testing protocol in healthy older adults, with implications for future efforts to facilitate accessible and sensitive cognitive screening for early detection of ADRD. Limitations include the restricted generalizability of this primarily white and college educated sample.

2 Vigilant Coping Moderates the Relationship between Discrimination and Memory among Black and Latinx Adults

Objective:In the U.S, Black and Latinx individuals disproportionately experience daily acts of discrimination. To counteract the psychological distress, many individuals develop coping mechanisms, like vigilant coping, where behaviors are modified to attempt to prevent discriminatory experiences. Researchers have investigated how coping mechanisms moderate the relationship between discrimination and psychological stress, but not their role in the relationship between discrimination and cognitive function. Prior research has shown a link between discrimination and poor episodic memory. The current study examined vigilant coping as a potential moderator in the relationship between discrimination and memory among Black and Latinx people.Participants and Methods:We partnered with 1317 non-Latinx Black (n= 291) and Latinx (n= 1026) individuals who participated in the Offspring Study of Racial and Ethnic Disparities in Alzheimer's Disease. Participants were assessed in English or Spanish, according to their preference. Experiences of discrimination were measured on two scales: Major (civil rights violations) and Everyday (daily hassles), and were coded according to yearly chronicity. Vigilance was measured among people with at least one reported experience of discrimination on either scale, using a 5-item survey which was dichotomized as low and high vigilant coping. The Selective Reminding Test, a 12-item word list task with 6 learning trials and a delayed recall trial, yielded scores for total immediate recall and delayed memory. Linear regression models were used to assess if vigilance moderated the relationship between discrimination and memory, with years of education and age as covariates.Results:Participants ranged in age from 27 to 91, with a mean age of 56.5 (SD=11.0) years, a mean education of 12.7 (SD=3.7) years, and were 67% women. High vigilant coping was associated with more experiences of major (b = 1.7, 95% CI = 0.9,2.5) and everyday (b = 90.3, 95% CI=66.2,114.3) discrimination. Memory was not associated with reported everyday discrimination, but lower delayed recall was observed among people who reported more experiences of major discrimination (b= -0.04, 95% CI = -0.07,-0.01). This relationship was moderated by vigilance, such that among people with low vigilant coping, major experiences of discrimination predicted lower memory (b= -0.06, 95% CI = -0.12,-0.01), but the association between discrimination and memory was weakened among people with high use of vigilant coping (b= -0.02, 95% CI = -0.05,0.01).Conclusions:This study builds on Black researchers' work that laid the foundations for examination of stress and coping in marginalized populations. Future studies on discrimination and cognitive health should consider coping mechanisms as key aspects of pathways linking structural racism and inequalities to cognitive health among Black and Latinx individuals.

36 Regional Amyloid and Memory in Amyloid Positive and Negative Older Adults

Objective:Alzheimer’s disease (AD) pathophysiology, including β-amyloid (Aβ), can be appreciated with molecular PET imaging. Among older adults, the distribution of Aβ standard uptake value ratios (SUVR) is typically bimodal and a diagnostic cut is applied to define those who are amyloid ‘positive’ and ‘negative’. However, it is unclear whether the dynamic range of SUVRs in amyloid positive and negative individuals is meaningful and associated with cognition. Previous work by Insel and colleagues (2020) used screening data from the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s (A4) trial to demonstrate subtle associations between a cortical summary SUVR and cognition, particularly on the Free and Cued Selective Reminding Test (FCSRT). We followed up this study to determine the extent to which regional SUVR is associated with performance on the FCSRT in amyloid positive and negative participants screened for participation in the A4 study.Participants and Methods:We accessed regional Aβ SUVR, including anterior cingulate, posterior cingulate, parietal, precuneus, temporal, and medial/orbital frontal regions, along with FCSRT15 and demographic data from 4492 A4 participants at screening. Participants were coded as amyloid positive (n=1329; 30%) or amyloid negative (n=3169; 70%) based on a summary SUVR of greater than or equal to 1.15. We used separate general linear models to examine the association of total or regional SUVR, amyloid positivity status, and the interaction of SUVR and amyloid status with FCSRT scores. We compared model fits across regions with the Akaike Information Criterion (AIC). We ran post hoc correlational analyses examining the relationship between SUVR and FCSRT scores stratified by amyloid status in the case of significant interactions. Results were similar with and without demographic adjustment.Results:There was a significant interaction of summary and all regional SUVR with FCSRT scores in addition to main effects of amyloid positivity. In all models, there were small negative associations between SUVR and memory in amyloid positive individuals. For amyloid negative individuals, there was a significant and very small negative association between SUVR and FCSRT scores only in the parietal lobes and precuneus regions. Model fits were generally similar across the different analyses.Conclusions:In this sample of individuals screened for a secondary prevention trial of AD, there were consistent associations between Aβ SUVR in all regions and memory for those considered amyloid positive. However, for individuals considered amyloid negative, there were only very small associations between SUVR and memory in parietal and precuneus regions. We conclude that the dynamic range of amyloid may be relevant among those with diagnostic evidence of amyloidosis, but that subtle Aβ accumulation in posterior regions may relate to declining memory in “subthreshold” states.

26 Religious Stress Coping, Memory, and Markers of Brain Pathology in Individuals with Autosomal Dominant Alzheimer’s Disease from the Colombia-Boston Biomarker Study

Objective:High levels of stress may increase risk for Alzheimer’s disease (AD) dementia. Religious coping practices to deal with stress (i.e., prayer, having faith, attending religious services) may reduce risk of dementia. Studying religious stress coping in cognitively unimpaired individuals with autosomal-dominant AD (ADAD), who will develop dementia later in life, may inform us about the role of religious coping in modifying the clinical trajectory from preclinical to clinical stages of the disease. We examined religious stress coping in cognitively unimpaired mutation carriers from the world’s largest ADAD kindred and its relation to markers of brain pathology and memory.Participants and Methods:16 cognitively unimpaired Presenilin-1 E280A mutation carriers and 19 age and education-matched noncarrier family members from the Colombia-Boston (COLBOS) Biomarker Study were included. A subsample (n=26; 13 cognitively unimpaired carriers) underwent amyloid and tau PET imaging. Participants completed the Coping Strategies Questionnaire (CAE) that includes a subscale used to assess religious stress coping, where a higher score indicates more coping, and underwent memory testing using the Free and Cued Selective Reminding Test (FCSRT). The Geriatric Depression Scale (GDS) was used to assess depression. Mann-Whitney U tests were used to examine group differences in religious stress coping, brain pathology (i.e., cortical amyloid-beta, entorhinal and precuneus tau), memory, and depression. Nonparametric correlations were used to examine associations among religious stress coping, age, education, depression, memory, and pathology.Results:Carriers had poorer FCSRT immediate free recall than noncarriers (U=84.5, p=.024). There was no difference between groups in CAE religious stress coping, other FCSRT memory scores, nor GDS score (all p&gt;.05). Compared to non-carriers, carriers had more cortical amyloid (U=152.0, p&lt;.001) and more precuneus tau (U=123.0, p=.05). In carriers, religious stress coping was positively associated with education (r=.57, p=.022), FCSRT immediate free recall (a=.75, p&lt;.001), FCSRT cued recall (a=.50, p=.047), and FCSRT delayed recall (r=.52, p=.038). After controlling for education, religious stress coping remained positively associated with FCSRT immediate free recall (r=.65, p=.009), but not other FCSRT memory scores (all p&gt;.05). Religious stress coping was not associated with age or GDS score regardless of controlling for education (all p&gt;.05). In carriers, religious stress coping was negatively associated with entorhinal tau (r=-.73, p=.005) and precuneus tau burden (r=-.58, p=.037). The association between religious stress coping and entorhinal tau remained significant after controlling for education (r=-.67, p=.016), but not precuneus tau (p&gt;.05). Religious stress coping was not associated with cortical amyloid regardless of controlling for education in carriers (all p&gt;.05). None of the associations with brain pathology or memory were significant in the non-carrier group.Conclusions:Religious stress coping was associated with better memory performance and a low AD pathology burden in individuals at genetic risk for developing AD dementia. Future studies with independent and larger samples should further examine religious stress coping strategies and their associations with other AD-related biomarkers, as well as with other risk and protective factors to better understand their role at the preclinical and prodromal stages of Alzheimer’s disease.

3 Does External Locus of Control Moderate the Intergenerational Transmission of Dementia Risk Among Non-Latinx Black and Non-Latinx White Middle-Aged Adults?

Objective:People whose parents had dementia or memory impairment are at higher risk for later-life cognitive impairment themselves. One goal of our research is to identify factors that either increase the risk of or protect against family history of dementia over the life course. External locus of control has been associated with lower cognitive function in middle-aged and older adults. Previous findings have shown that adults racialized as Black have relatively high levels of external locus of control due to inequity and racism. We hypothesized that lower parental memory would be associated with lower offspring memory among Non-Latinx Black and Non-Latinx White (hereafter Black and White, respectively) adults; and associations would be stronger among participants with higher levels of external locus of control.Participants and Methods:Participants comprised 594 adults racialized as Black or White (60.3% Black; 62% women; aged 56.1 ± 10.4; 15.3 ± 2.7 years of education) from the Offspring Study who are the adult children of participants in the Washington Heights Inwood Columbia Aging Project (WHICAP). Parental memory was residualized for age (74.3 ± 6.0) and education (13.7 ± 3.1). Self-reported external locus of control was assessed using 8 items from the the perceived control questionnaire. Memory was assessed with the Selective Reminding Test, and a composite of total and delayed recall scores were computed. Linear regression quantified the interaction between parental memory and external locus of control on memory in models stratified by race, and adjusted for age, sex/gender, and number of chronic health diseases.Results:Among Black participants (n=358), there were no main effects of parental memory or locus of control on offspring memory. However, lower parental memory was associated with lower offspring memory among Black participants with high levels of external locus of control (standardized estimate=0.36, p=0.02, 95%CI [0.05, 0.67]). Associations were attenuated and non-significant at lower levels of control. Among White participants (n=236), there was a main effect of parental memory on offspring memory, and this association did not vary by levels of external locus of control.Conclusions:Poor parental memory, which reflects risk for later-life cognitive impairment and dementia, was associated with lower memory performance among White middle-aged participants. Among Black participants, this association was observed among those with high levels of external locus of control only. Economic and social constraints shape levels of external locus of control and are disproportionately experienced by Black adults. In the face of greater external locus of control, a cascade of psychological and biological stress-related processes may be triggered and make Black adults’ memory function more vulnerable to the detrimental impact of parent-related dementia risk. Longitudinal analyses are needed to clarify temporal associations. Nonetheless, these findings suggest that reducing social and economic inequities disproportionately experienced by Black adults may dampen the effect of intergenerational transmission of dementia risk on cognition.

52 Memory Learning Curve and in vivo Brain Pathology in Non-Demented Individuals with Autosomal Dominant Alzheimer’s Disease: Findings from the Colombia-Boston Biomarker Study

Objective:Associative memory is impacted early in Alzheimer’s disease (AD). Poorer performance on associative memory tests has been related to greater amyloid and regional tau burden in preclinical AD. Our group previously examined the association of brain pathology and performance on the Free and Cued Selective Reminding Test (FCSRT) in Autosomal Dominant Alzheimer’s Disease (ADAD), finding that associative memory summary scores distinguished non-demented mutation carriers from non-carriers several years before clinical onset of cognitive impairment. In the current study, we examined whether FCSRT learning slopes were associated with brain pathology in a sample of ADAD carriers and non-carriers.Participants and Methods:There were 119 participants including 57 non-demented carriers of the Colombian kindred with the Presenilin1 E280A mutation and 62 non-carrier family members (mean age= 36.3, 60% female). Participants were administered the Mini-Mental State Examination (MMSE), a measure of global cognitive status, and the FCSRT, which consists of three trials in which participants are asked to freely recall the same list of 16 items. It is a well-established measure known to be sensitive to early changes in AD. A subsample of 69 participants (32 carriers and 37 non-carriers) underwent positron emission tomography (PET) to measure in vivo cortical amyloid-beta (Pittsburgh compound B, PiB), and regional tau (Flortaucipir, FTP) burden in entorhinal and precuneus regions, which are among the earliest sites of tau accumulation in this ADAD population. Mann Whitney U tests, Spearman correlations, and chi-square tests were used to examine group differences and relations among variables of interest. Learning slope was calculated by subtracting the number of items freely recalled in FCSRT Trial 1 from the number of items freely recalled in Trial 3.Results:Compared to non-carriers, carriers had greater cortical amyloid-ß and regional tau burden, lower MMSE scores (mean [SD]: carriers= 27.5 [2.7]; non-carriers= 28.8 [1.0]), and lower scores on total immediate/ delayed free/ cued recall scores on the FCSRT (all p&lt;.01). The groups did not differ on age, sex, or education level (all p&gt; 0.05). In the whole sample and in carriers only, we found that higher MMSE scores were associated with higher learning slope, meaning faster learning (whole group p= 0.25, p= 0.006; carriers p= 0.30, p=0.029). In the whole sample, we found that lower learning slope was associated with higher levels of amyloid (p=-.34, p=.006) and tau in the left, right, and bilateral precuneus region (p=-.43, p&lt;.001; p=-.46, p&lt;.001; p=-.45, p&lt;.001). In carriers only, lower learning slope was associated with higher tau burden in the left, right, and bilateral precuneus specifically (p=-.43, p=.017; p=-.48, p=.008; p=-.46, p=.010, respectively). No significant associations were found in non-carriers.Conclusions:These findings suggest that learning curves on an associative memory test may be sensitive to preclinical pathological changes in AD, specifically within the precuneus, a brain region known to be involved in cue reactivity, episodic memory retrieval, and mental imagery strategies. Future studies with larger samples are warranted to further examine associations between the FCSRT learning curves and regional tau accumulation in individuals with ADAD.

5 Longer Prospective Memory Delays Independently Predict Severity of Functional Decline in TBI

Objective:Prospective memory (PM) tasks are common in everyday life and have been implicated in optimal daily functioning. However, less is known about the parameters of PM tasks that most influence functional decline, as well as the domains of everyday functioning most sensitive to PM impairment. The present study sought to examine these questions in individuals with traumatic brain injury (TBI).Participants and Methods:Participants included 30 adults with chronic moderate-to-severe TBI who were at least one year removed from their injury (median [IQR] = 8.1 years [10.8]). Participants completed the Memory for Intentions Test (MIST), which is a 30-minute task that assesses time- and event-based PM with varying cue-intention delay length (2 versus 15 min) in the context of an ongoing task. Total scores were generated for each delay length and cue type. Additionally, participants completed a comprehensive neuropsychological battery, including assessments of processing speed, executive functions, attention, working memory, verbal fluency, and episodic learning and memory. Participants also completed questionnaires of self-reported cognitive and everyday functioning, including the Functional Behavior Profile (FBP), Prospective and Retrospective Memory Questionnaire (PRMQ) and a modified Lawton &amp; Brody Instrumental Activities of Daily Living (IADL) Scale, which separately assessed 11 domains of everyday functioning.Results:Pearson’s r correlations revealed that total number of domains showing decline on the modified Lawton &amp; Brody IADL scale was strongly correlated with MIST 15-min delay (MIST-15; r=-0.503, p=0.005), such that worse PM performance on long delay items was associated with more domains of IADL decline; this relationship was also reflected in the MIST Total Score (r=-0.389; p=0.033). No other MIST index was associated with IADL decline (ps&gt;0.10). MIST-15 did not significantly correlate with any other measure of self-reported functioning (PRMQ, FBP; all ps&gt;0.10), but was associated with specific declines in buying groceries (p=0.009), performing home repairs (p=0.021), shopping (p=0.033), and doing laundry (p=0.035). Relationships at a trend level included declines in housekeeping (p=0.05), managing finances (p=0.097), cooking (p=0.092), and taking medication (p=0.066). To determine specificity of the relationship between MIST-15 and everyday functioning, a linear regression was conducted using covariates that were significantly correlated with total number of domains of IADL decline (i.e., Selective Reminding Test total learning trials, CVLT-II Long Delay Free Recall, Symbol Digit Modalities Test total). This regression was statistically significant [F(4,24)=4.263; p=0.10; R2=0.415), and MIST-15 remained an independent predictor (p=0.047; R2 change=0.107).Conclusions:Results suggest that the ability to remember to carry out intended actions after longer delay periods may be uniquely related to severity of declines in everyday functioning. Longer PM delays place higher demands on both memory and executive processes, as the encoded intention must survive a longer decay wherein monitoring for the appropriate cue is extended, and likely better mimic PM tasks in daily life (e.g., remembering to pick up milk after the workday). In light of these findings, clinicians may seek to include brief trials of long delay PM tasks as part of a comprehensive battery to screen for functional decline.

Protein Plasma Levels of the IGF Signalling System Are Altered in Major Depressive Disorder.

The Insulin-like growth factor 2 (IGF-2) has been recently proven to alleviate depressive-like behaviors in both rats and mice models. However, its potential role as a peripheral biomarker has not been evaluated in depression. To do this, we measured plasma IGF-2 and other members of the IGF family such as Binding Proteins (IGFBP-1, IGFBP-3, IGFBP-5 and IGFBP-7) in a depressed group of patients (n = 51) and in a healthy control group (n = 48). In some of these patients (n = 15), we measured these proteins after a period (19 ± 6 days) of treatment with antidepressants. The Hamilton Depressive Rating Scale (HDRS) and the Self-Assessment Anhedonia Scale (SAAS) were used to measure depression severity and anhedonia, respectively. The general cognition state was assessed by the Mini-Mental State Examination (MMSE) test and memory with the Free and Cued Selective Reminding Test (FCSRT). The levels of both IGF-2 and IGFBP-7 were found to be significantly increased in the depressed group; however, only IGF-2 remained significantly elevated after correction by age and sex. On the other hand, the levels of IGF-2, IGFBP-3 and IGFBP-5 were significantly decreased after treatment, whereas only IGFBP-7 was significantly increased. Therefore, peripheral changes in the IGF family and their response to antidepressants might represent alterations at the brain level in depression.

The "when" matters: Evidence from memory markers in the clinical continuum of Alzheimer's disease.

Cognitive assessment able to detect impairments in the early neuropathological stages of Alzheimer's disease (AD) is urgently needed. The visual short-term memory binding task (VSTMBT) and the Free and Cued Selective Reminding Test (FCSRT) have been recommended by the neurodegenerative disease working group as promising tests to aid in the early detection of AD. In this study, we investigated their complementary value across the clinical stages of the AD continuum. One hundred and seventeen older adults with subjective cognitive complaint (SCC), 79 with mild cognitive impairment (MCI), 31 patients with AD dementia (ADD), and 37 cognitively unimpaired (CU) subjects, underwent assessment with the VSTMBT and the picture version of the Spanish FCSRT. After controlling for multiple comparisons, significant differences were found across groups. The VSTMBT was the only test that "marginally" differentiated between CU and SCC (d = 0.47, p = .052). Moreover, whereas the FCSRT showed a gradient (CU = SCC) > MCI > ADD, the VSTMBT gradient was CU > SCC > (MCI = ADD) suggesting that conjunctive binding deficits assessed by the latter may be sensitive to the very early stages of the disease. Our results suggest that the VSTMBT and the FCSRT are sensitive to the clinical continuum of AD. Whereas the former detects changes in the early prodromal stages, the latter is more sensitive to the advanced prodromal stages of AD. These novel tests can aid in the early detection, monitor disease progression and response to treatment, and thus support drug development programs. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Preliminary Findings on Cognitive Dysfunction in University-Educated Patients After Mild COVID-19 Disease

ObjectiveTo investigate cognitive functioning in patients with higher education having post COVID-19 condition. DesignProspective cohort study. SettingOutpatient rehabilitation clinic. ParticipantsPatients (N=38; mean age, 48.5y; 71% women) at the Cognitive Post COVID-19 Clinic at Danderyd University Hospital in Stockholm, Sweden, who sought health care because of self-experienced cognitive problems. All had at least 4 years of university education and an initially mild infection (ie, most were not hospital admitted, none were admitted to intensive care). InterventionsNot applicable. Main Outcome MeasuresCognitive test performance assessed with a comprehensive neuropsychological test battery including Information, Matrix Reasoning, Coding, and Digit Span from Wechsler's Adult Intelligence Scale-IV, Buschke Selective Reminding Test, Rey Complex Figure Test, Ruff 2&7, Color-Word Interference Test, Verbal Fluency, and Trail Making Test. The mean time between the infection and the assessment was 18 months. ResultsCognitive deficits were evident on tests of verbal learning and memory (Buschke Selective Reminding Test) and selective attention (Ruff 2&7). Approximately 50% of the participants had scores lower than 1 SD below the mean in the norm group on the measures of verbal learning and memory. When estimated premorbid cognitive functioning was accounted for, deficits were suggested in most cognitive domains. ConclusionsPost COVID-19 condition seems to be associated with cognitive deficits, even in patients with high education and an initially mild infection.

Normative Data for a Neuropsychological Test Battery in the French Aging Population: 20-Year Follow-Up From the "PROgnostic OF Cardiovascular and Cerebrovascular Events" Study.

The study aimed to present relevant norms for the evaluation of pathological aging in the French population over a 20-year period, utilizing the "PROgnostic OF cardiovascular and cerebrovascular events" test and questionnaire. Three neuropsychological evaluations were administered over 20years with 929 participants at the first cognitive evaluation (62-69years old), 631 at the second (71-78years old), and 293 at the third (81-88years old). The tests and questionnaires were administered in the following order: McNair's Cognitive Complaints Questionnaire, Depression Questionnaire of Pichot, Mini Mental State Examination, Free and Cued Selective Reminding test, Benton Visual Retention Test, Digit-Symbol Substitution Test of the WAIS-III, Trail Making Test, Stroop Test, Verbal Fluency, and the Similarities subtest of the WAIS-III. Normative data were presented at three time points of the repeated evaluation over 20years (62-69years, 71-78years, and 81-88years) and four educational levels (no diploma, primary school certificate, certificate of professional aptitude, and baccalaureate and above). The data showed a significant effect of educational level in all neuropsychological tests regardless of age. Gender primarily affected memory, Stroop scores, and Similarities scores. This study highlights the importance of educational level and gender in the evaluation of the memory and executive function of elderly persons. Furthermore, the presented norms consider the self-report cognitive complaints and depression symptoms over a long period of life.

A validation study for wide-range remote assessment of cognitive functions in the healthy older Japanese population: a pilot randomised crossover trial

BackgroundThe assessment of a wide range of cognitive functions using video teleconference (VTC) systems cannot be applied in practice yet. We aimed to determine the feasibility and reliability of previously unvalidated remote cognitive function tests in Japan using common information and communication technology (ICT) devices, software, and VTC systems compared with face-to-face (FTF) assessment.MethodsThe sample consisted of 26 participants from senior citizens clubs and an employment service centre in Sapporo Japan, including 11 females and 15 males (age averaged 78.6 ± 6.8 years). Tests included the RCPM, Story recall, 10/36 spatial recall, selective reminding test, SDMT, PASAT, FAB, TMT-A, TMT-B, visual cancellation task, digit span, tapping span. The experimental design was a counterbalanced crossover randomised controlled trial. Intraclass correlations (ICCs), paired-samples t-tests, Cohen’s Kappa (κ) coefficients, and Wilcoxon signed-rank test were calculated to compare the scores between VTC and FTF assessments.ResultsAll ICCs were significant and ranged from 0.47 (RCPM time) to 0.92 (RCPM score and PASAT), with a mean ICC of 0.75. Digit span using Cohen’s Kappa (κ) coefficient was significant, but the tapping span was not. Paired samples t-test showed statistically significant differences in SDMT, RCPM time, and cancellation time.ConclusionsThe results suggest that remote video conference-based neuropsychological tests even using familiar devices and software may be able to assess a wide range of cognitive functions in the Japanese older population. As for the processing speed tasks, we need to create our own standards for the remote condition. For the tapping span, we should consider increasing the number of trials.

Clinical and biochemical markers of neurodegenerative process in Alzheimer's disease

Recently, numerous studies have been devoted to describing the heterogeneity of Alzheimer's disease (AD). The aim of our work was to study the clinical, biochemical, and neuropsychological signs of AD depending on the form of the disease. The study involved 173 patients with AD, of whom 65 patients with early onset and 108 with late onset at the stage of moderate cognitive impairment. All study participants underwent the Montreal Cognitive Assessment Scale (MoCA test), the Free and Cued Selective Reminding Test with Immediate Recall (FCSRT-IR), and a lumbar puncture with the determination of the levels of Aβ42 and Aβ40 biomarkers in the cerebrospinal fluid by enzyme immunoassay. The mean age of the patients with early onset of AD was 65.1±0.3 years, and with late onset - 78.6±0.5 years. According to our data, it was found that the majority of the patients with late-onset AD had a longer education (p=0.000) and had coffee more often (p=0.000) than the study participants with early onset of AD. We did not reveal the effect of alcohol and smoking on the neurodegenerative process. The patients with early-onset AD scored lower on the MoCA test than those with late-onset AD (p=0.000). The results of free recall and cue index on the FCSRT-IR test in the patients with late AD were significantly lower than in the patients with early AD onset (p&lt;0.001). We found that the level of Aβ42 and the ratio of Aβ42/Aβ40 in the cerebrospinal fluid was significantly lower (p=0.000) in the patients with early AD onset. The results of our study prove the need for an integrated approach to diagnosing AD using clinical, neuropsychological,and biochemical research methods.

Brain structure and phenotypic profile of superagers compared with age-matched older adults: a longitudinal analysis from the Vallecas Project

Cognitive abilities, particularly memory, normally decline with age. However, some individuals, often designated as superagers, can reach late life with the memory function of individuals 30 years younger. We aimed to characterise the brain structure of superagers and identify demographic, lifestyle, and clinical factors associated with this phenotype. We selected cognitively healthy participants from the Vallecas Project longitudinal cohort recruited between Oct 10, 2011, and Jan 14, 2014, aged 79·5 years or older, on the basis of their delayed verbal episodic memory score. Participants were assessed with the Free and Cued Selective Reminding Test and with three non-memory tests (the 15-item version of the Boston Naming Test, the Digit Symbol Substitution Test, and the Animal Fluency Test). Participants were classified as superagers if they scored at or above the mean values for a 50-56-year-old in the Free and Cued Selective Reminding Test and within one standard deviation of the mean or above for their age and education level in the three non-memory tests, or as typical older adults if they scored within one standard deviation of the mean for their age and education level in the Free and Cued Selective Reminding Test. Data acquired as per protocol from up to six yearly follow-ups were used for longitudinal analyses. We included 64 superagers (mean age 81·9 years; 38 [59%] women and 26 [41%] men) and 55 typical older adults (82·4 years; 35 [64%] women and 20 [36%] men). The median number of follow-up visits was 5·0 (IQR 5·0-6·0) for superagers and 5·0 (4·5-6·0) for typical older adults. Superagers exhibited higher grey matter volume cross-sectionally in the medial temporal lobe, cholinergic forebrain, and motor thalamus. Longitudinally, superagers also showed slower total grey matter atrophy, particularly within the medial temporal lobe, than did typical older adults. A machine learning classification including 89 demographic, lifestyle, and clinical predictors showed that faster movement speed (despite no group differences in exercise frequency) and better mental health were the most differentiating factors for superagers. Similar concentrations of dementia blood biomarkers in superager and typical older adult groups suggest that group differences reflect inherent superager resistance to typical age-related memory loss. Factors associated with dementia prevention are also relevant for resistance to age-related memory decline and brain atrophy, and the association between superageing and movement speed could provide potential novel insights into how to preserve memory function into the ninth decade. Queen Sofia Foundation, CIEN Foundation, Spanish Ministry of Science and Innovation, Alzheimer's Association, European Research Council, MAPFRE Foundation, Carl Zeiss Foundation, and the EU Comission for Horizon 2020. For the Spanish translation of the abstract see Supplementary Materials section.