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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
- Defne Yucebas, Paula Aduen, Ana Baena, Francisco Lopera, Alice Cronin-Golomb, Yakeel T Quiroz
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 564-565
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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<.01). The groups did not differ on age, sex, or education level (all p> 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<.001; p=-.46, p<.001; p=-.45, p<.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.
69 Evaluation of Ethnoracial Differences in Self- and Study-Partner Reported Subjective Cognitive Decline
- Talia L Robinson, Hannah M Klinger, Rachel F Buckley, Kacie D Deters, Yakeel T Quiroz, Dorene M Rentz, Reisa A Sperling, Rebecca E Amariglio
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 374-375
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Objective:
1) Evaluate the association of self- and study-partner report of subjective cognitive decline (SCD) to objective cognitive performance across ethnoracial groups. 2) Evaluate the concordance of self- and study partner report of SCD across ethnoracial groups.
Participants and Methods:Participants were 5241 non-Hispanic White (NHW), 267 non-Hispanic Black (NHB), 225 Hispanic, and 228 Asian participants screened for the A4 study (N=5961). Participants completed the Preclinical Alzheimer Cognitive Composite (PACC), and self- and study partner-report of SCD using the Cognitive Function Index (CFI). Analysis of variance was used to assess difference in key variables by ethnoracial group. Regression analyses were conducted to evaluate the association of SCD and objective performance by ethnoracial group, and the association between self-and study partner report of SCD by ethnoracial group.
Results:Asian participants reported the highest mean CFI relative to all other groups, while NHW reported the lowest (F(3,5957)=41.93, p <.001). Asian and NHW participants had higher PACC scores relative to NHB and Hispanic participants (F(3,5957)=41.93, p <.001). Regression analyses revealed higher CFI was associated with lower PACC score across groups, and this association was strongest in the Asian sample relative to other groups (F(10, 5897)=40.49, p<.001,R2=.06). Evaluation of study partner characteristics suggested NBH participants had the highest proportion on non-spousal study partners relative to other groups. Regression analyses revealed no differences in the association of self- and study partner report of SCD across ethnoracial groups (F(10, 5859)=132.9, p<.001, R2=0.18).
Conclusions:Results suggest that that SCD is associated with objective cognitive performance across racial groups, although the strength of this association appears to vary in this sample. There is also consistent concordance between self- and study partner report of SCD across groups, despite differences in study partner relationships. SCD may be considered a valid predictor of subtle cognitive change across groups in the A4 sample. Limitations include small group sizes relative to the large NHW sample. Future work with larger, more representative samples are needed to further validate these findings.
12 Purpose in Life, Loneliness, and Subjective Cognitive Decline in an Ethnically Diverse US Sample
- Celina F. Pluim, Juliana A. U. Anzai, Jairo E. Martinez, Diana Munera, A. Paola Garza-Naveda, Clara Vila-Castelar, Edmarie Guzmán-Vélez, Liliana Ramirez-Gomez, Julian Bustin, Cecilia M. Serrano, Ganesh M. Babulal, Maira Okada de Oliveira, Yakeel T. Quiroz
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 326-327
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Objective:
Subjective cognitive decline (SCD), the self-reported experience of worsening cognitive abilities (Jessen et al., 2014), is associated with increased risk of developing Alzheimer’s disease and Mild Cognitive Impairment. Modifiable factors such as purpose in life (PiL), the experience of living a meaningful life where one’s life goals are attainable or being achieved (Boyle et al., 2009), and loneliness, an individual’s perceived social isolation (Luhmann & Hawkley, 2016), are known to be associated with SCD. These relationships are understudied among ethnically diverse groups. Using an online survey, we examined associations between PiL, loneliness and SCD in older ethnically diverse individuals living in the US.
Participants and Methods:870 older adults (126 Latino, 74 Black, 33 Asian, and 637 White; average age=67.0 [7.6]) completed an online survey including the Life Purpose Questionnaire, the Gierveld Loneliness Scale, and the Everyday Cognition scale (ECog), which measures subjective cognitive concerns in memory, language, executive function, and divided attention. Chi-square tests and analyses of variance were conducted to assess group differences in SCD and demographic/lifestyle predictors. Multiple regressions and correlations were conducted to assess the relationships between ethnicity and PiL with SCD, and the moderating effect of race/ethnicity. Multiple regressions and correlations were conducted to identify sociodemographic and lifestyle predictors of SCD in each study group.
Results:White participants were older (p<.001), and White and Asian groups had higher levels of education (p=.009) compared to Latinos. The White group had a higher proportion of female (p=.016) and middle-income (p=.019) respondents. Black participants had higher PiL (p=.035) and lower loneliness (p=.047) compared to White participants; there were no group differences in ECog ratings (p=.143). Regression results indicated that higher PiL associated with lower SCD in the whole sample (β=-.435, p<.001). The interaction between PiL and ethnic group was significant (β=.078, p=.025), suggesting the relationship between PiL and SCD was strongest in White participants, followed by Asian, then Latino, and finally Black participants. In Latinos, female sex (β=-.281, p=.004) and higher PiL (β=-.240, p=.034) predicted lower SCD ratings. In White participants, higher PiL (β = -.394, p < .001), and lower loneliness (β = .128, p = .003) predicted lower SCD ratings. Correlation analyses revealed no significant associations with SCD in the Black group, although the correlation between loneliness and SCD was trending (r=.222, p=.063). In the Asian group, greater PiL was associated with lower SCD ratings (r=-.439, p=.011).
Conclusions:Our findings suggest that PiL may be protective against SCD, particularly in Latino, Asian, and White adults. Differential predictive factors of SCD were also identified for our study groups, suggesting certain groups may benefit from specific targeted interventions. Overall, findings suggest that interventions geared toward increasing PiL and/or mitigating loneliness may help reduce SCD and the risk of cognitive decline in older adults in the US. As the current study was cross-sectional and faced sample size limitations in Asian and Black groups, future studies should include longitudinal assessment of these associations with larger and more representative samples to confirm our findings.
37 The MAPP Room Memory Task: Examining Contextual Memory Using a Novel Computerized Task in Cognitively-Unimpaired Individuals with Autosomal Dominant Alzheimer’s Disease from the Colombia-Boston Biomarker Study
- Lyda M Arevalo Gonzalez, Jairo E Martinez, Paula Aduen, Joshua Fox-Fuller, Ana Baena, Clara Vila-Castelar, Francisco Lopera, Yakeel T Quiroz
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 245-246
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Objective:
Contextual memory, which refers to the ability to remember spatial or temporal circumstances related to an event, is affected early in Alzheimer’s Disease (AD). Computerized cognitive tasks have been suggested to be an ecological way to assess memory, but there are few studies that utilize these tools. Studying contextual memory via a computerized task in a Colombian kindred with autosomal dominant AD due to the Presenilin-1 (PSEN1) E280A mutation and a well-characterized disease progression may help us understand contextual memory changes in the preclinical AD stage. In this study we investigated whether a novel computerized task examining contextual memory can help identify those at increased risk for dementia.
Participants and Methods:A group of 31 non-carriers (mean age=38.97±6.11; mean education=11.45±4.34) and 15 cognitively unimpaired PSEN1E280A mutation carriers from the Colombia-Boston (COLBOS) Biomarker Study (mean age=35.67±5.50), mean education=10.60±3.83) performed the “MAPP Room Memory Task” on a computer. As part of this task, participants are asked to remember ten rooms and the specific location of a few objects for later recall. During the immediate recall phase, participants are asked to recognize the objects presented in each room (Immediate Object Recognition) and their location (Immediate Object Placement). During the subsequent delay phase of the task, participants are asked to select the correct room in which an object was first presented (Delayed Room Recognition) and place the objects previously seen in each room (Delayed Object Placement). We conducted Mann Whitney U tests to analyze differences between groups and Spearman Rho correlations to examine associations among the Room Memory Task performance, age, education, and Mini Mental State Examination (MMSE).
Results:There were no differences in age or education between carriers and non-carriers (p>0.05, for both). Carriers had worse Delayed Room Recognition than non-carriers (Carriers mean score=0.893±0.18, non-carriers mean score=0.987±0.05; U=168.0, p=0.02), while there were no differences in the other task conditions (all p>0.05). In carriers, education was positively associated with Immediate Object Placement (rs=0.61, p=0.02), Delayed Object Placement (rs=0.76, p=0.001), and Delayed Room Recognition (rs=0.68, p=0.006). There were no significant associations between Room Memory Task conditions and age or MMSE scores in carriers. Further, no significant associations were observed between Room Memory Task performance, and age, education or MMSE scores in non-carriers.
Conclusions:Our preliminary findings show that the MAPP Room Memory Task, in particular the Delayed Room Recognition condition, may be helpful to discriminate those at increased risk of dementia. Future studies with larger samples using the Room Memory Task and AD-related biomarkers are needed to examine whether this task can be sensitive to early preclinical changes associated with AD and can potentially help track disease progression in those at risk.
26 Religious Stress Coping, Memory, and Markers of Brain Pathology in Individuals with Autosomal Dominant Alzheimer’s Disease from the Colombia-Boston Biomarker Study
- Jairo E Martinez, Yamile Bocanegra, Ana Baena, Paula Aduen, Alice Cronin-Golomb, Francisco Lopera, Yakeel T Quiroz
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 236-237
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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>.05). Compared to non-carriers, carriers had more cortical amyloid (U=152.0, p<.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<.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>.05). Religious stress coping was not associated with age or GDS score regardless of controlling for education (all p>.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>.05). Religious stress coping was not associated with cortical amyloid regardless of controlling for education in carriers (all p>.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.
22 Semantic Processing and its Relation to Brain Pathology in Individuals with Autosomal Dominant Alzheimer's Disease: Preliminary Findings from the Colombia-Boston Biomarker Study
- Gladiliz Rivera-Delpin, Clara Vila-Castelar, Ana Baena, Crystal Castillo, Jairo E Martinez, Claudia Penaloza, Francisco Lopera, Yakeel T Quiroz
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, p. 232
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Objective:
Semantic processing dysfunction has been shown to be an early indicator of cognitive decline in Alzheimer's disease (AD) and has been linked to early accumulation of AD-pathology. We examined semantic processing and its relation to AD pathology in non-demented individuals from a Colombian kindred with autosomal dominant AD due to the Presenilin1 E280A mutation (PSEN1).
Participants and Methods:A total of 13 cognitively unimpaired PSEN1 mutation carriers (mean age: 36.92± 4.94), 7 carriers with mild cognitive impairment (MCI; mean age: 45±2.65), and 17 family non-carriers (mean age: 36±6.38) from the Colombia-Boston (COLBOS) longitudinal biomarker study were included. We used the Bateria IV Woodcock-Munoz verbal analogies and text comprehension subtests to examine semantic processing, the Mini-Mental State Examination (MMSE) to assess global cognition and the CERAD word list delayed recall task to measure verbal memory. Participants also underwent PiB and flortaucipir-PET to measure mean cortical amyloid and regional tau burden (entorhinal cortex and precuneus), respectively. Mann-Whitney U tests and Spearman's Rho correlations compared group differences in semantic processing, and its associations with age and pathological markers. Post-hoc analyses excluded carriers with MCI and controlled for education.
Results:Carriers (including cognitively unimpaired and symptomatic individuals) performed significantly worse on the MMSE (carriers: 14.55, non-carriers: 24.24; U=81.00, p=.006), CERAD word list delayed recall (carriers: 13.63, non-carriers: 25.32; U=48.00, p=.001), and text comprehension (carriers: 16.36, non-carriers: 23.81; l/=107.00, p=.042,) than non-carriers, and showed a trend towards worse performance on verbal analogies (carriers: 17.16, non-carriers: 23.68; U=124.50, p=.077). There were no differences in text comprehension or verbal analogies performance between cognitively-unimpaired carriers and non-carriers.Across the whole sample, age was negatively associated with performance on verbal analogies (r=-.341, p=.039), but not text comprehension (r=-.136, p=.428). Among carriers only, better MMSE and CERAD delayed recall performance was associated with higher verbal analogies (r=.561, p=<.001; r=.662, p=<.001, respectively) and text comprehension scores (r=.468, p=.004; r=.480, p=.003, respectively). Greater amyloid burden was associated with worse verbal analogies performance (r=-.432, p=.007) and text comprehension (r=-.430, p=.008). Greater entorhinal cortex (r=-.384, p=.016) and precuneus tau burden (r=-.318, p=.049) was associated with worse performance on verbal analogies, but not text comprehension. These associations did not survive when excluding carriers with MCI or controlling for education.
Conclusions:Preliminary results show that non-demented mutation carriers had worse performance in semantic processing than non-carriers and performance was associated with markers of AD pathology. These findings suggest that changes in semantic processing may be early indicators of disease progression in individuals at increased risk for Alzheimer's disease dementia. Future studies with larger samples need to examine the role of education and the longitudinal trajectory of semantic processing dysfunction in AD.
97 Looking in the Webcam Reflection: A Scoping Review of Videoconferencing-Based Teleneuropsychological Assessment Since the Start of the COVID-19 Pandemic
- Joshua T Fox-Fuller, Preeti Sunderaraman, C. Munro Cullum, Yakeel T. Quiroz
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 770-771
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Objective:
Following the start of the SARS-COV-2 (COVID-19) pandemic there was a rapid uptake in teleneuropsychology (TeleNP). Many clinicians and researchers used videoconferencing technologies (e.g., Zoom®) to conduct remote neuropsychological assessments. Prior reviews (e.g., Marra et al., 2020) have indicated promise for the use of videoconference-based approaches to cognitive assessment under certain circumstances, though arguably nobody foresaw the widespread use of teleNP during the pandemic. Given the rapid expansion in the teleNP literature in the past couple of years, in this scoping review we specifically discuss research updates made during the COVID-19 pandemic pertaining to teleNP assessment of adults conducted via videoconferencing and their potential clinical applications.
Participants and Methods:GoogleScholar and PubMed were used to search for peer-reviewed original research articles published between January 1, 2020 (i.e., the approximate beginning of the COVID-19 pandemic) and August 1, 2022. Broad search terms were used pertaining to teleNP, remote cognitive assessment, videoconferencing, and neuropsychological assessment, resulting in 16 articles.
Results:Though most of the included studies were based in the United States (n=5), there was international representation across studies (Chile=1; United Kingdom=1; Australia=2; New Zealand=1; France=2; Greece=1; Japan=2, Singapore=1). All of the identified articles examined TeleNP-related research questions using cognitive tests administered via videoconferencing that have been previously studied in-person to varying degrees. Several of the studies focused on psychometric characterization (i.e., reliability and validity) of the examined tests when delivered via videoconferencing, whereas others focused on demonstrating the relative equivalence of neuropsychological scores obtained via videoconferencing versus in-person evaluations.
Conclusions:Formal psychometric studies of traditional in-person neuropsychological tests delivered via videoconferencing since the start of the COVID-19 pandemic suggest that this remote modality of assessment is generally reliable and valid. Moreover, multiple recent studies have demonstrated relative equivalence of neuropsychological scores obtained via videoconferencing versus neuropsychological test scores obtained in-person. When considered alongside teleNP research conducted prior to the COVID-19 pandemic (e.g. Cullum et al., 2014), recent studies on videoconference-based neuropsychological assessment indicate that videoconferencing may not necessarily be a complete substitute for an in-person comprehensive evaluation given the inherent limitations of the procedure. However, teleNP via videoconferencing may be a promising tool in the neuropsychologist’s toolbox because it can help reduce common barriers to in-person neuropsychological assessment (e.g., travel time to clinics). Additional research on videoconferencing-based cognitive assessment is needed, especially in low-and-middle income countries (LMIC) and diverse populations where there may be more economic barriers to remote neuropsychological assessment relative to more economically-developed countries. Notably it is possible that research from LMIC may have been missed through the screening processes used in this review (e.g., inclusion of articles written in English).
33 Associations Between Long-Term Forgetting and Slow Wave Activity in Autosomal-Dominant Alzheimer’s Disease: Findings from the Colombia-Boston (COLBOS) Biomarker Study
- Daisy T Noriega, Ana Baena, Diana Munera, Enmanuelle Pardilla-Delgado, Paula Aduen, Clara Vila-Castelar, Stephanie Langella, Liliana Ramirez-Gomez, Celina Pluim, Eric M Reiman, Francisco Lopera, Alice D Lam, Yakeel T Quiroz
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 908-909
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Sleep contributes to memory retention and recall. Alzheimer’s disease (AD) patients experience decreased slow wave activity (SWA) during sleep. This decrease in SWA is associated with impaired memory consolidation (Lee et al., 2020). Long-term forgetting (LTF) over days or weeks has been linked to memory consolidation deficits and has been suggested as an early marker of AD that could be useful for identifying at-risk individuals for preclinical AD trials (Weston et al., 2018). Here, we examined associations between LTF and SWA in a sample of Presenilin-1 (PSEN1) E280A mutation carriers with autosomal dominant Alzheimer’s disease and non-carrier family members. Carriers of this mutation usually develop dementia in their forties (Fuller et al., 2019).
Participants and Methods:Fourteen cognitively unimpaired PSEN1-E280A mutation carriers and sixteen age-matched non-carriers (mean age: 34.2 years) from the Colombia-Boston (COLBOS) biomarker study were included. Participants completed an overnight polysomnogram (PSG) and memory testing (NEUROPSI Word List) at 3-time points: 1) the night before PSG: immediate recall (Day1-ImmRecall) and a 20-minute delayed recall (Day1-DelayedRecall), 2) recall the following day (Day2-recall), and 3) recall one week later (Day7-recall). SWA was measured as the ratio 0. 6-1Hz/0.6-4Hz in frontopolar and frontotemporal regions and was calculated for sleep stages N2+N3 (slow wave sleep) based on an automated staging algorithm. Each participant’s LTF was calculated as the percent retention between Day 1 immediate recall and Day 7 recall (Butler, 2009). Mann-Whitney U tests were used to compare differences in recall, SWA, and LTF between groups. Spearman’s correlation was used to examine the associations between memory recall at different time points and SWA, as well as between LTF and SWA.
Results:On Day 1, carriers had lower performance in immediate recall (p=0.02), compared to non-carriers, but there were no group differences in the 20-minute delayed recall. Carriers also recalled fewer words on Day 2 (p=0.03) and Day 7 (p=0.009) and had greater LTF (p=0.03). There were no group differences in SWA. In our overall sample, worse performance on word list delayed recall on Day 1, Day 2, and Day 7 was associated with less SWA across both frontotemporal (Day1: p=0.04, Day2: p=0.02, Day7: p=0.02) and frontopolar (all Ps<0.01) regions. In carriers, only worse performance on Day 1 delayed recall was associated with lower SWA in the frontopolar region (r= 0.535; p=0.049). Memory recall on other days was not associated with SWA in any brain regions. Additionally, greater LTF was associated with less SWA across both frontopolar (r= 0.507; p=0.005) and frontotemporal regions (r= 0.463 p= 0.01).
Conclusions:Preliminary findings suggest that long-term forgetting is associated with less slow- wave activity in preclinical autosomal dominant Alzheimer’s disease. These results also suggest that SWA may be related to pre-sleep learning and subsequent overnight memory consolidation processes. LTF testing may be useful in selecting individuals for preclinical AD trials. Future research on the impact of slow wave activity on LTF may be useful in identifying ways to enhance short- and long-term memory consolidation in individuals at greater risk for dementia.
94 Physical Activity, Emotional Functioning, and Cognitive Concerns During the COVID-19 Pandemic Among Older Adults in the US
- Perla K. Ortiz-Acosta, Edmarie Guzmán-Vélez, Valeria Torres, Jairo E. Martínez, Ana Baena, Diana Munera, Enmanuelle Pardilla-Delgado, Celina Pluim, Ganesh Babulal, Liliana Ramírez-Gómez, Clara Vila-Castelar, Joshua Fox Fuller, Yakeel T. Quiroz
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 394-395
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Objective:
Physical inactivity is associated with a greater risk of frailty, neuropsychiatric symptoms, worse quality of life, and increased risk for Alzheimer’s disease. Little is known about how physical activity engagement of older adults during the COVID-19 pandemic relates to subjective cognitive concerns and management of emotional distress. This study aimed to examine whether there were changes in physical activity during the pandemic in older adults at baseline and 3 months compared to before the pandemic and whether these changes varied based on age, sex, income level, and employment status. Further, we examined whether individuals who reported engaging in less physical activity experienced greater subjective cognitive difficulties and symptoms of depression and anxiety than those who maintained or increased their physical activity levels.
Participants and Methods:301 participants (73% non-Hispanic whites) completed an online survey in either English or Spanish between May and October 2020 and 3 months later. The Everyday Cognition Scale was used to measure subjective cognitive decline, the CES-D-R-10 scale to measure depressive symptoms, and the GAD-7 scale to measure anxiety symptoms. Changes in physical activity were measured with the question “Since the coronavirus disease pandemic began, what has changed for you or your family in regard to physical activity or exercise levels?” with options “less physical activity,” “increase in physical activity,” or “same activity level.” Income was self-reported as high, middle, or low. Analyses of chi-squared tests were used to examine differences in physical activity maintenance by age, income level, sex, and employment status.
Results:Most individuals (60%) reported having decreased their physical activity levels during the pandemic, at baseline and 3-month followup. There were differences in physical activity levels based on income and age: participants with a high income reported engaging in more physical activity than those with low income (X^2=4.78, p =.029). At the 3-month follow-up, middle-income participants reported being less active than the high-income earners (X^2=8.92, p=.003), and younger participants (55-65 years, approximately) reported being less active than older participants (X^2=5.28, p =.022). Those who reported an increase in their physical activity levels had fewer cognitive concerns compared to those who were less active at baseline, but this difference was not seen in the 3-month follow-up. Participants of all ages who reported having maintained or increased their physical activity levels had fewer depressive symptoms than those who were less active (p < 0.0001). Those who reported maintaining their physical activity levels exhibited fewer anxiety symptoms than those who were less active (p < 0.01).
Conclusions:Older adults reported changes in physical activity levels during the pandemic and some of these changes varied by sociodemographic factors. Further, maintaining physical activity levels was associated with lower symptoms of depression, anxiety, and cognitive concerns. Encouraging individuals and providing resources for increasing physical activity may be an effective way to mitigate some of the pandemic’s adverse effects on psychological wellbeing and may potentially help reduce the risk for cognitive decline. Alternately, it is possible that improving emotional distress could lead to an increase in physical activity levels and cognitive health.
4 Association Between Plasma Neurofilament Light Chain (NfL) and Non-Verbal Abstract Reasoning in a Colombian Cohort with Autosomal Dominant Alzheimer’s Disease
- Alex Leonardo Badillo Cabrera, Paula A Aduen, Jairo E. Martinez, Ana Baena Pineda, Victoria Tirado, Paula Ospina, Francisco Lopera, Yakeel T Quiroz
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 216-217
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Objective:
Neurofilament light chain (NfL), a plasma-based biomarker for neurodegeneration, is a promising marker for early Alzheimer disease (AD) detection in individuals at increased risk. We previously reported that Presenilin1 (PSEN1) E280A carriers have increased levels of plasma NfL relative to non-carrier family members twenty years before the onset of clinical symptoms. Abstract reasoning is one of the first cognitive abilities to deteriorate in AD. Here, we examined whether levels of plasma NfL were associated with non-verbal abstract reasoning performance in non-demented PSEN1-E280A carriers and non-carriers.
Participants and Methods:A total of 798 members of the Colombian kindred with the PSEN1 E280A mutation (462 cognitively-unimpaired and 336 non-carriers; mean age= 34.02 (10.53), mean education= 8.23(4.60), 57% females and 43% males) were included in the study. Participants completed the Raven’s Progressive Matrices (RPM), Mini Mental State Examination (MMSE), and underwent blood sampling. Plasma NfL concentrations were measured with a single molecule array (Simoa) method. Mann-Whitney U test and education-adjusted Spearman partial correlation were used to examine group differences and associations between abstract reasoning performance and NfL levels.
Results:Non-carriers were older (p<.001) and had higher levels of education than carriers (p=.025). Compared to non-carriers, carriers had higher levels of NfL (p=.014), lower performance on the MMSE (p<.001) and on the RPM (p=.001). In the whole sample, performance on the RPM was significantly associated with age (r= -.144, p<.001), and MMSE score (r=.198, p<.001). In carriers only, performance on the RPM was negatively associated with NfL levels (r=-.121, p=.009). This association was not significant in non-carriers.
Conclusions:Our findings support the hypothesis that plasma NfL levels may be indicators of disease progression and early cognitive dysfunction in autosomal dominant AD. Future work with NfL, abstract reasoning and memory with larger samples across the preclinical/prodromal spectrum will allow a more comprehensive examination of these associations.
Associations of category fluency clustering performance with in vivo brain pathology in autosomal dominant Alzheimer’s disease
- Defne Yucebas, Joshua T. Fox-Fuller, Alex Badillo Cabrera, Ana Baena, Celina Pluim McDowell, Paula Aduen, Clara Vila-Castelar, Yamile Bocanegra, Victoria Tirado, Justin S. Sanchez, Alice Cronin-Golomb, Francisco Lopera, Yakeel T. Quiroz
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- Journal:
- Journal of the International Neuropsychological Society / Volume 30 / Issue 1 / January 2024
- Published online by Cambridge University Press:
- 26 April 2023, pp. 77-83
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Objectives:
Alzheimer’s disease (AD) is known to impact semantic access, which is frequently evaluated using the Category Fluency (Animals) test. Recent studies have suggested that in addition to overall category fluency scores (total number of words produced over time), poor clustering could signal AD-related cognitive difficulties. In this study, we examined the association between category fluency clustering performance (i.e., stating words sequentially that are all contained within a subcategory, such as domestic animals) and brain pathology in individuals with autosomal dominant Alzheimer’s disease (ADAD).
Methods:A total of 29 non-demented carriers of the Presenilin1 E280A ADAD mutation and 32 noncarrier family members completed the category fluency test (Animals) and the Mini-Mental State Examination (MMSE). The participants also underwent positron emission tomography (PET) scans to evaluate in vivo amyloid-beta in the neocortex and tau in medial temporal lobe regions. Differences between carriers and noncarriers on cognitive tests were assessed with Mann-Whitney tests; associations between cognitive test performance and brain pathology were assessed with Spearman correlations.
Results:Animal fluency scores did not differ between carriers and noncarriers. Carriers, however, showed a stronger association between animal fluency clustering and in vivo AD brain pathology (neocortical amyloid and entorhinal tau) relative to noncarriers.
Conclusion:This study indicates that using category fluency clustering, but not total score, is related to AD pathophysiology in the preclinical and early stages of the disease.
Subjective Cognitive Decline and its Relation to Verbal Memory and Sex in Cognitively Unimpaired Individuals from a Colombian Cohort with Autosomal-Dominant Alzheimer’s Disease
- Jairo E. Martinez, Enmanuelle Pardilla-Delgado, Edmarie Guzmán-Vélez, Clara Vila-Castelar, Rebecca Amariglio, Jennifer Gatchel, Daniel C. Aguirre-Acevedo, Yamile Bocanegra, Ana Baena, Eliana Henao, Victoria Tirado, Claudia Muñoz, Margarita Giraldo-Chica, Francisco Lopera, Yakeel T. Quiroz
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- Journal:
- Journal of the International Neuropsychological Society / Volume 28 / Issue 6 / July 2022
- Published online by Cambridge University Press:
- 30 June 2021, pp. 541-549
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Objective:
Subjective Cognitive Decline (SCD) may be an early indicator of risk for Alzheimer’s disease (AD). Findings regarding sex differences in SCD are inconsistent. Studying sex differences in SCD within cognitively unimpaired individuals with autosomal-dominant AD (ADAD), who will develop dementia, may inform sex-related SCD variations in preclinical AD. We examined sex differences in SCD within cognitively unimpaired mutation carriers from the world’s largest ADAD kindred and sex differences in the relationship between SCD and memory performance.
Methods:We included 310 cognitively unimpaired Presenilin-1 (PSEN-1) E280A mutation carriers (51% females) and 1998 noncarrier family members (56% females) in the study. Subjects and their study partners completed SCD questionnaires and the CERAD word list delayed recall test. ANCOVAs were conducted to examine group differences in SCD, sex, and memory performance. In carriers, partial correlations were used to examine associations between SCD and memory performance covarying for education.
Results:Females in both groups had greater self-reported and study partner-reported SCD than males (all p < 0.001). In female mutation carriers, greater self-reported (p = 0.02) and study partner-reported SCD (p < 0.001) were associated with worse verbal memory. In male mutation carriers, greater self-reported (p = 0.03), but not study partner-reported SCD (p = 0.11) was associated with worse verbal memory.
Conclusions:Study partner-reported SCD may be a stronger indicator of memory decline in females versus males in individuals at risk for developing dementia. Future studies with independent samples and preclinical trials should consider sex differences when recruiting based on SCD criteria.
The INECO Frontal Screening for the Evaluation of Executive Dysfunction in Cerebral Small Vessel Disease: Evidence from Quantitative MRI in a CADASIL Cohort from Colombia – Corrigendum
- Dorothee Schoemaker, Yesica Zuluaga, Anand Viswanathan, Markus D. Schirmer, Heirangi Torrico-Teave, Lina Velilla, Carolina Ospina, Gloria Garcia Ospina, Francisco Lopera, Joseph F. Arboleda-Velasquez, Yakeel T. Quiroz
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- Journal:
- Journal of the International Neuropsychological Society / Volume 26 / Issue 10 / November 2020
- Published online by Cambridge University Press:
- 24 September 2020, p. 1052
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Association Between Visual Memory and In Vivo Amyloid and Tau Pathology in Preclinical Autosomal Dominant Alzheimer’s Disease
- Yamile Bocanegra, Joshua T. Fox-Fuller, Ana Baena, Edmarie Guzmán-Vélez, Clara Vila-Castelar, Jairo Martínez, Heirangi Torrico-Teave, Francisco Lopera, Yakeel T. Quiroz
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- Journal:
- Journal of the International Neuropsychological Society / Volume 27 / Issue 1 / January 2021
- Published online by Cambridge University Press:
- 07 August 2020, pp. 47-55
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Objective:
Visual memory (ViM) declines early in Alzheimer’s disease (AD). However, it is unclear whether ViM impairment is evident in the preclinical stage and relates to markers of AD pathology. We examined the relationship between ViM performance and in vivo markers of brain pathology in individuals with autosomal dominant AD (ADAD).
Methods:Forty-five cognitively unimpaired individuals from a Colombian kindred with the Presenilin 1 (PSEN1) E280A ADAD mutation (19 carriers and 26 noncarriers) completed the Rey–Osterrieth Complex Figure immediate recall test, a measure of ViM. Cortical amyloid burden and regional tau deposition in the entorhinal cortex (EC) and inferior temporal cortex (IT) were measured using 11C-Pittsburgh compound B positron emission tomography (PET) and 11F-flortaucipir PET, respectively.
Results:Cognitively unimpaired carriers and noncarriers did not differ on ViM performance. Compared to noncarriers, carriers had higher levels of cortical amyloid and regional tau in both the EC and IT. In cognitively unimpaired carriers, greater cortical amyloid burden, higher levels of regional tau, and greater age were associated with worse ViM performance. Only a moderate correlation between regional tau and ViM performance remained after adjusting for verbal memory scores. None of these correlations were observed in noncarriers.
Conclusions:Results suggest that AD pathology and greater age are associated with worse ViM performance in ADAD before the onset of clinical symptoms. Further investigation with larger samples and longitudinal follow-up is needed to examine the utility of ViM measures for identifying individuals at high risk of developing dementia later in life.
The INECO Frontal Screening for the Evaluation of Executive Dysfunction in Cerebral Small Vessel Disease: Evidence from Quantitative MRI in a CADASIL Cohort from Colombia
- Dorothee Schoemaker, Yesica Zuluaga, Anand Viswanathan, Markus Shrimer, Heirangi Torrico-Teave, Lina Velilla, Carolina Ospina, Gloria Garcia Ospina, Francisco Lopera, Joseph F. Arboleda-Velasquez, Yakeel T. Quiroz
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- Journal:
- Journal of the International Neuropsychological Society / Volume 26 / Issue 10 / November 2020
- Published online by Cambridge University Press:
- 03 June 2020, pp. 1006-1018
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Objectives:
Executive dysfunction is a predominant cognitive symptom in cerebral small vessel disease (SVD). The Institute of Cognitive Neurology Frontal Screening (IFS) is a well-validated screening tool allowing the rapid assessment of multiple components of executive function in Spanish-speaking individuals. In this study, we examined performance on the IFS in subjects with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), an inherited condition leading to the early onset of SVD. We further explored associations between performance on the IFS and magnetic resonance imaging (MRI) markers of SVD.
Methods:We recruited 24 asymptomatic CADASIL subjects and 23 noncarriers from Colombia. All subjects underwent a research MRI and a neuropsychological evaluation, including the IFS. Structural MRI markers of SVD were quantified in each subject, together with an SVD Sum Score representing the overall burden of cerebrovascular alterations. General linear model, correlation, and receiver operating characteristic curve analyses were used to explore group differences on the IFS and relationships with MRI markers of SVD.
Results:CADASIL subjects had a significantly reduced performance on the IFS Total Score. Performance on the IFS correlated with all quantified markers of SVD, except for brain atrophy and perivascular spaces enlargement. Finally, while the IFS Total Score was not able to accurately discriminate between carriers and noncarriers, it showed adequate sensitivity and specificity in detecting the presence of multiple MRI markers of SVD.
Conclusions:These results suggest that the IFS may be a useful screening tool to assess executive function and disease severity in the context of SVD.