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32 Elevated Plasma pTau-181 is Associated with Lower Global Cognition and Executive Function in Older Adults
- Arunima Kapoor, Jean K Ho, Shubir Dutt, Yanrong Li, John P Alitin, Jung Yun Jang, Aimee Gaubert, Amy Nguyen, Belinda Yew, Anna E Blanken, Isabel J Sible, Anisa Marshall, Fatemah Shenasa, Alessandra Martini, Kathleen E Rodgers, Elizabeth Head, Daniel A Nation
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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. 907-908
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Objective:
Aggregation of phosphorylated tau (pTau) is a hallmark feature of Alzheimer’s disease (AD). Novel assays now allow pTau to be measured in plasma. Elevated plasma pTau predicts subsequent development of AD, cortical atrophy and AD-related pathologies in the brain. We aimed to determine whether elevated pTau is associated with cognitive functioning in older adults prior to the development of dementia.
Participants and Methods:Independently living older adults (N = 48, mean age = 70.0 years; SD = 7.7; age range 55-88 years; 35.4% male) free of dementia or clinical stroke were recruited from the community and underwent blood draw and neuropsychological assessment. Plasma was assayed using the Quanterix Simoa® pTau-181 V2 Advantage Kit to quantify pTau-181 levels and APOE genotyping was conducted on the blood cell pellet fraction obtained from plasma separation. Global cognition was assessed using the Dementia Rating Scale-2 (DRS-2) and executive function was assessed using the Stroop, D-KEFS-2 Fluency, and Trails Making Test. Diagnosis of mild cognitive impairment (MCI) was determined based on overall neuropsychological performance. Participants were diagnosed as MCI if they scored >1 SD below norm-referenced values on 2 or more tests within a domain (language, executive, memory) or on 3 tests across domains.
Results:Multiple linear regression analysis revealed a significant negative association between plasma pTau-181 levels and DRS-2 (B = -2.57, 95% CI (-3.68, -1.47), p <.001), Stroop Color-Word score (B = -2.64, 95% CI (-4.56, - 0.71), p = .009) and Fruits and Vegetables Fluency (B = -1.67, 95% CI (-2.84, -0.49), p = .007), adjusting for age, sex, education and APOE4 status. MCI diagnosis was determined for 43 participants, of which 8 (18.6%) met criteria. Logistic regression analysis revealed that pTau-181 levels are associated with increased odds of MCI diagnosis (OR = 2.18, 95% CI (1.01, 4.68), p = .046), after accounting for age, sex, education and APOE4 status.
Conclusions:Elevated plasma pTau-181 is associated with worse cognition, particularly executive function, and predicts MCI diagnosis in older adults. Higher plasma pTau-181 was associated with increased odds of MCI diagnosis. Detection of pTau-181 in plasma allows a novel, non-invasive method to detect burden of one form of AD pathology. These findings lend support to the use of plasma pTau-181 as a valuable marker in detecting even early cognitive changes prior to the development of AD. Additional longitudinal studies are warranted to explore the prognostic value of plasma pTau-181 over time.
49 Examining Associations Between Intelligence and Adaptive Functioning in Adults with Down Syndrome at Risk for Alzheimer's Disease
- Sheliza Ali, Jordan Harp, Allison M. Caban-Holt, Brandon Dennis, Elizabeth Head, Jennifer Wells, Frederick Schmitt
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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. 256-257
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Objective:
Individuals with Down syndrome (DS) experience intellectual disability, such that measures of cognitive and adaptive functioning are near the normative floor upon evaluation. Individuals with DS are also at increased risk for Alzheimer's disease (AD) beginning around age 40; and test performances and adaptive ratings at the normative floor make it difficult to detect change in cognition and functioning. This study first assessed the range of raw intelligence scores and raw adaptive functioning of individuals with DS at the normative floor. Next, we assessed whether those raw intelligence scores were predictive of raw adaptive functioning scores, and by association, whether they may be meaningful when assessing change in individuals with a lower baseline of cognitive functioning.
Participants and Methods:Participants were selected from a cohort of 117 adults with DS in a longitudinal study examining AD risk. Participants (n=96; M=40.9 years-old, SD=10.67; 57.3% female) were selected if they had both a completed measure of IQ (Kaufmann Brief Intelligence Test; KBIT2) and informant ratings of adaptive functioning (Vineland Adaptive Behavior Scales; VABS-II). Multiple regression was conducted predicting VABS-II total raw score using K-BIT2 total raw score, while controlling for age.
Results:A slight majority (57.3%) of the sample had a standardized IQ score of 40 with the majority (95.7%) having a standardized score at or below 60. Additionally, 85.3% of the sample had a standard VABS-II score at or below 60. Within the normative floor for the KBIT2 (IQ=40), there was a normal distribution and substantial range of both KBIT2 raw scores (M = 31.19, SD = 13.19, range: 2 to 41) and VABS-II raw scores (M = 406.33, SD = 84.91, range: 198 to 569). Using the full sample, age significantly predicted raw VABS-II scores (ß = -.283, p = .008). When KBIT2 raw scores were included in the model, age was no longer an independently significant predictor. KBIT2 raw scores significantly predicted raw VABS-II scores (ß = .689, p < .001). Age alone accounted for 8.0% of variance in VABS-II raw scores and KBIT2 raw scores accounted for 43.8% additional variance in VABS-II raw scores. This relationship was maintained when the sample was reduced to individuals at the normative floor (n = 51) where KBIT2 raw scores accounted for 23.7% of the variance in raw VABS-II scores (ß = .549, p < .001).
Conclusions:The results indicate that meaningful variability exists among raw intelligence test performances that may be masked by scores at the normative floor. Further, the variability in raw intelligence scores is associated with variability in adaptive functioning, such that lower intelligence scores are associated with lower ratings of adaptive functioning. Considering this relationship would be masked by a reduction of range due to norming, these findings indicate that raw test performances and adaptive functioning ratings may have value when monitoring change in adults with DS at risk for AD.
5 Associations Between Regional Perfusion and Locus Coeruleus MRI Contrast are Moderated by Plasma Alzheimer’s Disease Biomarkers in Older Adults
- Shubir Dutt, Shelby L Bachman, Yanrong Li, Belinda Yew, Jung Y Jang, Jean K Ho, Kaoru Nashiro, Jungwon Min, Hyun Joo Yoo, Aimee Gaubert, Amy Nguyen, Isabel J Sible, Anna E Blanken, Anisa J Marshall, Arunima Kapoor, John P Alitin, Kim Hoang, Alessandra C Martini, Elizabeth Head, Xingfeng Shao, Danny J J Wang, Mara Mather, Daniel A Nation
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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. 610-611
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Objective:
The locus coeruleus (LC) innervates the cerebrovasculature and plays a crucial role in optimal regulation of cerebral blood flow. However, no human studies to date have examined links between these systems with widely available neuroimaging methods. We quantified associations between LC structural integrity and regional cortical perfusion and probed whether varying levels of plasma Alzheimer’s disease (AD) biomarkers (Aß42/40 ratio and ptau181) moderated these relationships.
Participants and Methods:64 dementia-free community-dwelling older adults (ages 55-87) recruited across two studies underwent structural and functional neuroimaging on the same MRI scanner. 3D-pCASL MRI measured regional cerebral blood flow in limbic and frontal cortical regions, while T1-FSE MRI quantified rostral LC-MRI contrast, a well-established proxy measure of LC structural integrity. A subset of participants underwent fasting blood draw to measure plasma AD biomarker concentrations (Aß42/40 ratio and ptau181). Multiple linear regression models examined associations between perfusion and LC integrity, with rostral LC-MRI contrast as predictor, regional CBF as outcome, and age and study as covariates. Moderation analyses included additional terms for plasma AD biomarker concentration and plasma x LC interaction.
Results:Greater rostral LC-MRI contrast was linked to lower regional perfusion in limbic regions, such as the amygdala (ß = -0.25, p = 0.049) and entorhinal cortex (ß = -0.20, p = 0.042), but was linked to higher regional perfusion in frontal cortical regions, such as the lateral (ß = 0.28, p = 0.003) and medial (ß = 0.24, p = 0.05) orbitofrontal (OFC) cortices. Plasma amyloid levels moderated the relationship between rostral LC and amygdala CBF (Aß42/40 ratio x rostral LC interaction term ß = -0.31, p = 0.021), such that as plasma Aß42/40 ratio decreased (i.e., greater pathology), the strength of the negative relationship between rostral LC integrity and amygdala perfusion decreased. Plasma ptau181levels moderated the relationship between rostral LC and entorhinal CBF (ptau181 x rostral LC interaction term ß = 0.64, p = 0.001), such that as ptau181 increased (i.e., greater pathology), the strength of the negative relationship between rostral LC integrity and entorhinal perfusion decreased. For frontal cortical regions, ptau181 levels moderated the relationship between rostral LC and lateral OFC perfusion (ptau181 x rostral LC interaction term ß = -0.54, p = .004), as well as between rostral LC and medial OFC perfusion (ptau181 x rostral LC interaction term ß = -0.53, p = .005), such that as ptau181 increased (i.e., greater pathology), the strength of the positive relationship between rostral LC integrity and frontal perfusion decreased.
Conclusions:LC integrity is linked to regional cortical perfusion in non-demented older adults, and these relationships are moderated by plasma AD biomarker concentrations. Variable directionality of the associations between the LC and frontal versus limbic perfusion, as well as the differential moderating effects of plasma AD biomarkers, may signify a compensatory mechanism and a shifting pattern of hyperemia in the presence of aggregating AD pathology. Linking LC integrity and cerebrovascular regulation may represent an important understudied pathway of dementia risk and may help to bridge competing theories of dementia progression in preclinical AD studies.
A Roman Pond at Wyre Piddle, Worcestershire, with a Brief Survey of Ponds in Roman Britain
- Derek Hurst, Nicholas Daffern, Laura Griffin, Katie Head, Andrew Mann, Elizabeth Pearson, Sylvia Warman
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Artificial Roman ponds present in various guises, but they are relatively rarely found in the service of rural agriculture. This article focuses on a possible example of this type from Worcestershire, where extensive excavation has been carried out. The results demonstrate the potential of a pond for the reconstruction of wider landscape usage, while the considerable quantity of associated finds potentially sheds some light on social practice. A review of similar sites across Roman Britain suggests there may be practical (in essence curatorial) issues about the fuller investigation of such features once identified, in order that a similarly high level of data can be achieved more regularly, and suggests a need for prospection/mapping for the better management of this resource, especially employing newly available LiDAR data.