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6 Exercise Induced Growth Factor Increases Directly and Indirectly Reduce Systemic Vascular Risk Parameters: Translational Project Amongst Midlife Human and Animal Models of Preclinical Alzheimer’s disease and Vascular Dementia
- Amanda Hewes, Kate Foley, Jennifer Thompson, Lindsey Lagerstrom, Taylor Mcmillan, Gareth Howell, Fayeza Ahmed
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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. 218-219
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Objective:
Using a humanized APOE3/4 (Alzheimer’s disease genetic risk allele) mouse model we investigated the potential modulating effects of exercise on systemic risk factors and the ability of this mouse model to translate to active or sedentary, midlife, human participants. We present preliminary results of an ongoing, translational pilot study.
Participants and Methods:26 Midlife individuals, ages 40-65, were recruited from the community and dichotomized into active or sedentary groups following health screening and cognitive assessment. Blood samples were drawn from human participants for lipid assessment and other general health measures as well as peripheral growth factors concentrations (VEGF, BDNF and FGF21). Traditional, transgenic mouse models have helped the scientific community to understand biological mechanisms of Alzheimer’s disease (AD), but they do not develop significant neuronal loss, a hallmark of AD pathology. The MODEL-AD consortium has created a new “humanized” APOE4 model that has the human APOE4 allelic sequence in place of the mouse APOE gene; the model has shown known human phenotypes including deficits in cholesterol trafficking, amyloid clearance and BBB integrity. Of upmost importance, this model does not develop a full AD phenotype indicating that additional genetics and/or environmental factors are required as would be seen in human populations. We used males and females of this model to complete identical sedentary and active measures of each APOE genotype.
Results:Lipid and general health marker assessment between mouse and human were similar and reproduced published literature. In both humans and mice we saw increased total cholesterol and HDL in active females and decreased total cholesterol and HDL in active males. We also saw similar relationships between APOE genotype, sex, and activity with regards to triglycerides. Although total cholesterol, HDL and LDL measures are the primary lipids needed to confirm or deny translation, other lipid measurements were not equivalent between the two models. Growth factor assessment in both species are also similar and reproduce published literature with regards to VEGF and BDNF as we see trending elevated levels in the active group. Less published on is the finding seen between active females and these elevated growth factors levels; our results indicates that although elevated as a result of exercise, this increase may be more prominent in females.
Conclusions:Based on the results found here we conclude that The Jackson Laboratory’s humanized APOE3/4 mouse model is a translatable model of vascular dysfunction, dementia and Alzheimer’s disease. We also conclude that exercise modulates these aspects by growth factor activation and increases resulting in downstream effects that reduce peripheral vascular risk factors and therefore reduce the risk of Alzheimer’s disease as a result of neuroinflammation. Complete, APOE genotype results from human participants are still ongoing. Descriptive analysis is limited by human samples size.
72 Dietary Fat and Measures of Attention and Learning in Middle-Aged Adults
- Taylor M McMillan, Fayeza S Ahmed
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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. 376-377
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Objective:
Research examining dietary fat in relation to physical and cognitive health is mixed. Generally, it has been hypothesized that polyunsaturated fatty acids (PUFAs) have vascular, anti-inflammatory, and neuroprotective effects1,2,3. Monounsaturated fatty acids (MUFAs) commonly occur with saturated fatty acids (SFA) in certain foods, and some research suggests that consumption is associated with increased vascular risk4; however, there is limited research examining combined MUFAs and SFAs consumption from traditional Western diet foods (e.g., pizza, desserts) compared to animal (e.g., butter, cow milk, salmon) and plant products (e.g., coconut oil, cocoa butter). Furthermore, much of the research examining dietary components/supplementation and cognition is in older adult or at-risk samples, with limited research examining the relationships among middle-aged and cognitively unimpaired adults. We present preliminary data from an ongoing pilot study.
Participants and Methods:39 middle-aged (40-65 years, inclusive) cognitively unimpaired individuals were recruited from the community. The Food Frequency Questionnaire (Short-Form; SF-FFQ) was used to calculate diet components and servings during a “typical week.” Attention and working memory were measured using trial one of the California Verbal Learning Test - Third Edition (CVLT-III), Oral Trail Making Test Part B, Number Span (forward and backward), Stroop Color and Color-Word trials. Genetic and other plasma-based data for 25 participants have also been obtained, and analysis is in progress; we plan to analyze these additional components in greater detail once we have achieved our target sample size.
Results:Nonparametric correlation analyses revealed no significant relationships between total dietary fat (as measured by the SF-FFQ) and cognitive performance, which included CVLT Trial 1 (r = .28, p = .09), Oral Trail Making Test Part B (r = .02, p = .89), Number Span Forward (r = .18, p = .27) and Number Span Backward (r = -.04, p = .83), Stroop Color trial (r = -.10, p = .56), and Stroop Color-Word trial (r = -.09, p = .58). Notably, however, data is continuing to be collected and these relationships will be examined further with additional data.
Conclusions:While total fat consumption was expected to be associated with attention and working memory measures, correlations revealed nonsignificant relationships. Notably, there are important limitations to consider, as other expected relationships based on previous research findings/theoretical relationships (e.g., positive correlation between waist-to-hip ratio and fat consumption) were lacking. A primary limitations of this study included a small sample size of cognitive and physically healthy middle-aged adults. Regardless, these relationships should be explored further with a greater and more diverse sample size.
71 Sleep Quality and Measures of Attention and Learning in Middle-Aged Adults
- Jennifer L Thompson, Casey J Kneissler, Jacob D Tucker, Fayeza S Ahmed
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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. 580-581
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Objective:
Sleep has been shown to directly impact cognitive function throughout the lifespan; good quality sleep benefits and improves cognitive function, including processing speed and attention, while poor quality sleep can contribute to negative cognitive outcomes1. In particular, attention, learning, and memory have been demonstrated to be sensitive to sleeping changes, including fragmentation and restriction2. Subjective sleeping scales are utilized in both research and clinical practice, allowing sleep to be measured via self-report on various domains, including duration and factors that can contribute to sleep disruption and disturbances3. This study aims to examine the possible relation between subjective sleep quality and cognitive function among middle-aged adults to inform future research for early interventions of modifiable behaviors that can contribute to abnormal cognitive decline.
Participants and Methods:Data for this analysis is part of the preliminary results of an ongoing pilot study. 29 middle-aged (40-65 years, inclusive), cognitively unimpaired individuals were recruited from the community. Subjective sleep quality was measured with the Pittsburgh Sleep Quality Index (PSQI). Attention and memory were measured using the California Verbal Learning Test, Third Edition (CVLT-III).
Results:Multiple hierarchical regression analyses were conducted to evaluate if aspects of sleep quality were significantly correlated to complex attention and learning performance in this sample. First, correlation amylases showed significant relationships between PSQI Component 6 (Use of Sleeping Medication) and Trials 1 to 2 Learning Slope (R2 = -0.56, p =0.002) and CVLT-III Trials 1 through 5 Recall Discriminability (R2 = -0.42, p = 0.02), each with significant regression analyses outcomes (b =0.42, p = 0.04 and b = -0.46, p = 0.04, respectively). There were other variables that were found to be significantly correlated; however, after adjusting for relevant demographic variables (age, education, sex), the hierarchical regression analyses revealed no association between the aforementioned variables.
Conclusions:While multiple aspects of sleep quality were expected to influence measures of attention and learning, only PSQI Component 6 was found to be statistically significantly associated with only two learning variables. Limitations of this study included a small sample size which was limited to cognitive and relatively physically healthy middle-aged adults. Further, sleep quality was measured with one subjective measure and no objective data was collected to support the hypotheses. Future analysis is needed to continue to explore the relation between subjective sleep quality and cognitive outcomes. As this is an ongoing study, we look forward to exploring this research question in more detail as the study progresses.
Two Novel Psychomotor Tasks in Idiopathic Normal Pressure Hydrocephalus
- Maria A. Rossetti, Irene Piryatinsky, Fayeza S. Ahmed, Petra M. Klinge, Norman R. Relkin, Stephen Salloway, Lisa D. Ravdin, Einat Brenner, Paul F. Malloy, Bonnie E. Levin, Michael Broggi, Rebecca Gavett, James S. Maniscalco, Heather Katzen
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- Journal:
- Journal of the International Neuropsychological Society / Volume 22 / Issue 3 / March 2016
- Published online by Cambridge University Press:
- 28 January 2016, pp. 341-349
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Objective: Idiopathic normal pressure hydrocephalus (INPH) is a neurological disorder presenting with gait, cognitive, and bladder symptoms in the context of ventricular enlargement. Although gait is the primary indicator for treatment candidacy and outcome, additional monitoring tools are needed. Line Tracing Test (LTT) and Serial Dotting Test (SDT), two psychomotor tasks, have been introduced as potential outcome measures but have not been widely studied. This preliminary study examined whether LTT and SDT are sensitive to motor dysfunction in INPH and determined if accuracy and time are important aspects of performance. Methods: Eighty-four INPH subjects and 36 healthy older adults were administered LTT and SDT. Novel error scoring procedures were developed to make scoring practical and efficient; interclass correlation showed good reliability of scoring procedures for both tasks (0.997; p<.001). Results: The INPH group demonstrated slower performance on SDT (p<.001) and made a greater number of errors on both tasks (p<.001). Combined Time/Error scores revealed poorer performance in the INPH group for original-LTT (p<.001), modified-LTT (p≤.001) and SDT (p<.001). Conclusions: These findings indicate LTT and SDT may prove useful for monitoring psychomotor skills in INPH. While completion time reflects impaired processing speed, reduced accuracy may suggest planning and self-monitoring difficulties, aspects of executive functioning known to be compromised in INPH. This is the first study to underscore the importance of performance accuracy in INPH and introduce practical/reliable error scoring for these tasks. Future work will establish reliability and validity of these measures and determine their utility as outcome tools. (JINS, 2016, 22, 341–349)