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4 Impact of APOE-ε Alleles on Brain Structure and Function in Healthy Older Adults: A VBM and DTI Replication Study
- Colleen Lacey, Jodie Gawryluk, Theone Paterson
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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. 882-883
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Objective:
The Apolipoprotein E (APOE) gene has been established in the Alzheimer’s disease (AD) literature to impact brain structure and function and may also show congruent effects in healthy older adults, although findings in this population are much less consistent. Magnetic Resonance Imaging (MRI), Diffusion Tensor Imaging (DTI), and neuropsychological measures present as useful, non-invasive tools to investigate the impact of APOE-e allele status on grey matter structure, white matter integrity, and cognitive functioning, respectively. Nonetheless, studies to date have revealed mix findings and few studies have taken a multimodal approach to investigating APOE’s effects. Thus, the objective of the current study was to replicate and expand upon the multimodal neuroimaging study conducted by Honea et al. (2009), that examined the impact of APOE-e4 presence on brain structure and cognitive function in healthy older adults, with the addition of APOE-e2 carriers and cognitive composite measures. The aim of the current replication study was to identify reliable changes to grey matter volume and white matter integrity in healthy older adults as it relates to APOE-e allele presence and cognitive performance. This represents one of the first studies to investigate both the risk and protective effects of APOE-e alleles (e4 and e2 respectively) on measures of cognitive performance, GMV and white matter integrity in healthy older adults.
Participants and Methods:Data were obtained from the Alzheimer’s Disease Initiative phase 3 (ADNI3) database. Baseline MRI, DTI and cognitive composite scores for memory (ADNI-Mem) and executive function (ADNI-EF) were acquired from 116 healthy controls. Participants were grouped according to APOE allele presence (APOE-e2+ N= 17, APOE-e3e3 N= 64, APOE-e4+ N=35). Voxel-based morphometry (VBM) and tract based spatial statistics (TBSS) were used to compare grey matter volume (GMV) and white matter integrity respectively between APOE-e2+ and APOE-e3e3 controls, and again between APOE-e4+ and APOE-e3e3 controls. Multivariate analysis of covariance (MANCOVA) was used to examine the effects of APOE polymorphism on memory and EF across all APOE groups with covariates of age, sex, education, and cognitive scores were correlated with imaging metrics within groups (Pearson r) to examine associations between cognitive performance and brain structure.
Results:Consistent with findings from Honea et al. (2009), no significant differences were seen across APOE groups, within-groups in MRI metrics, or cognitive performance (p>0.05, corrected for multiple comparisons). Taking a similar approach to Honea and company, nonsignificant, trend-level results were examined (p<0.2, corrected for multiple comparisons) and suggested: 1) Decreased GMV and increased mean diffusivity (MD) were present in APOE-e4+ compared to APOE-e3e3 and 2) Increased GMV and fractional anisotropy (FA) were present in APOE-e2+ compared to APOE-e3e3.
Conclusions:The current study replicated and extended previous findings. Trend-level findings across both the current and replicated study suggests there may be subtle neurostructural differences in healthy aging as a function of APOE-e4 status. The current study additionally found potential subtle differences in GMV and white matter integrity in APOE-e2 carriers at the trend-level, consistent with previous reports of APOE-e2 's protective effects against neurodegeneration. Although these findings should be interpreted with caution, trend-level effects seen in the current study are consistent with previous research and may hold important implications for APOE neuromechanisms.
48 Sex Differences and Longitudinal Changes in White Matter Microstructure in Healthy Older Adults
- Lisa Ohlhauser, Stuart MacDonald, Jodie Gawryluk
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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. 920-921
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Objective:
As the global population of older adults increases, it is crucial to study the healthy aging brain. Despite representing approximately 50% of brain tissue, investigations of changes in white matter (WM) have been limited. Given that women outlive men in most populations worldwide, evaluating factors such as sex and gender in the normal aging trajectory are particularly important. However, past research has been limited by varying definitions of these terms and methodological challenges. Further, limited studies have employed longitudinal designs. The objective of the present study was to 1) compare sex similarities and differences in WM microstructure, and 2) investigate longitudinal changes in WM in healthy older adults. The Parkinson’s Progression Markers Initiative (PPMI) is an ongoing observational longitudinal study designed to investigate biomarkers related to Parkinson’s disease. For up-to-date information, please see: https://www.ppmi-info.org/. The PPMI study presents a convenient opportunity to investigate the expected aging trajectory among healthy older adults by using data from its healthy control cohort.
Participants and Methods:Participants (N=40) included 16 females (mean age = 60.50 + 5.99) and 24 males (mean age = 65.50 + 7.53) from the healthy control cohort of the PPMI. Diffusion tensor imaging (DTI) data from two time points (baseline and approximately one year later) were analyzed using tract-based spatial statistics from the FMRIB Software Library (FSL). Diffusion weighted images were acquired with a Siemens 3T TIM Trio scanner with a 12 channel Matrix head coil. All images were acquired with a spin echo, echo planar imaging sequence with 64 gradient directions and a b-value of 1000s/mm2 with a voxel size of 2 mm3. Two analyses were conducted: 1) between-groups, comparing differences in WM microstructure between males and females at baseline while controlling for age and total brain volume (TBV), and 2) within-subject, examining longitudinal changes in WM from baseline to one year later. DTI metrics included fractional anisotropy (FA) and mean diffusivity (MD).
Results:Males were significantly older than females and had significantly larger TBVs. Results of voxelwise comparisons revealed no statistically significant differences in FA or MD between males and females when controlling for age and TBV. Longitudinally over one year, decreases in MD (p<.05, corrected) were found in the right superior and inferior longitudinal fasciculus, the right corticospinal tract, and the right inferior fronto-occipital fasciculus. Stability in FA was observed over one year. There was also an average of a one-point decline on the Montreal Cognitive Assessment during the study period of one year.
Conclusions:No significant sex differences in WM microstructure were found, which agrees with a published review of the literature that men and women show very similar brain structure after accounting for brain size differences. Across the entire sample, longitudinal changes in WM were captured via neuroimaging across a one-year time frame. Follow-up exploration of these data suggests great intraindividual variability in trajectories over time, which may have affected the overall group trajectory. Continued research of factors that contribute to the identifying individual healthy aging trajectories is warranted.