Table_1_Apolipoprotein E Genotype e2: Neuroprotection and Its Limits.pdf

In this review, we comprehensively, qualitatively, and critically synthesized several features of APOE-e2, a known APOE protective variant, including its associations with longevity, cognition, and neuroimaging, and neuropathology, all in humans. If e2’s protective effects—and their limits—could be elucidated, it could offer therapeutic windows for Alzheimer’s disease (AD) prevention or amelioration. Literature examining e2 within the years 1994–2021 were considered for this review. Studies on human subjects were selectively reviewed and were excluded if observation of e2 was not specified. Effects of e2 were compared with e3 and e4, separately and as a combined non-e2 group. Our examination of existing literature indicated that the most robust protective role of e2 is in longevity and AD neuropathologies, but e2’s effect on cognition and other AD imaging markers (brain structure, function, and metabolism) were inconsistent, thus inconclusive. Notably, e2 was associated with greater risk of non-AD proteinopathies and a disadvantageous cerebrovascular profile. We identified multiple methodological shortcomings of the literature on brain function and cognition that could have contributed to inconsistent and potentially misleading findings. We make careful interpretations of existing findings and provide directions for research strategies that could effectively examine the independent and unbiased effect of e2 on AD risk.</p

CDR-SB progression over time for pooled AD studies and pooled MCI studies.

For both AD and MCI studies, the non-practice effects group progressed faster.</p

Sample size comparison for different sample size estimation methods (based on 80% power, 5% type I error, two-sided test, equal duration).

The left panel estimated the sample size by assuming the same minimum clinical meaningful difference; whereas the right panel by assuming the same percentage reduction in the progression of the placebo group. Sample size were estimated based on two-sample t-tests.</p

Estimated mean ADAS-Cog₁₁ over time for pooled AD/MCI studies.

Similar results to those individual studies were observed for the mean ADAS-Cog11 over time.</p

Comparison between practice effects group and non-practice effects group.

Comparison between practice effects group and non-practice effects group.</p

Table_3_The Age-Related Perfusion Pattern Measured With Arterial Spin Labeling MRI in Healthy Subjects.DOCX

Aim: To analyze age-related cerebral blood flow (CBF) using arterial spin labeling (ASL) MRI in healthy subjects with multivariate principal component analysis (PCA).Methods: 50 healthy subjects (mean age 45.8 ± 18.5 years, range 21–85) had 3D structural MRI and pseudo-continuous ASL MRI at resting state. The relationship between CBF and age was examined with voxel-based univariate analysis using multiple regression and two-sample t-test (median age 41.8 years as a cut-off). An age-related CBF pattern was identified using multivariate PCA.Results: Age correlated negatively with CBF especially anteriorly and in the cerebellum. After adjusting by global value, CBF was relatively decreased with aging in certain regions and relatively increased in others. The age-related CBF pattern showed relative reductions in frontal and parietal areas and cerebellum, and covarying increases in temporal and occipital areas. Subject scores of this pattern correlated negatively with age (R2 = 0.588; P Conclusion: A distinct age-related CBF pattern can be identified with multivariate PCA using ASL MRI.</p

Image_3_The Age-Related Perfusion Pattern Measured With Arterial Spin Labeling MRI in Healthy Subjects.PDF

Aim: To analyze age-related cerebral blood flow (CBF) using arterial spin labeling (ASL) MRI in healthy subjects with multivariate principal component analysis (PCA).Methods: 50 healthy subjects (mean age 45.8 ± 18.5 years, range 21–85) had 3D structural MRI and pseudo-continuous ASL MRI at resting state. The relationship between CBF and age was examined with voxel-based univariate analysis using multiple regression and two-sample t-test (median age 41.8 years as a cut-off). An age-related CBF pattern was identified using multivariate PCA.Results: Age correlated negatively with CBF especially anteriorly and in the cerebellum. After adjusting by global value, CBF was relatively decreased with aging in certain regions and relatively increased in others. The age-related CBF pattern showed relative reductions in frontal and parietal areas and cerebellum, and covarying increases in temporal and occipital areas. Subject scores of this pattern correlated negatively with age (R2 = 0.588; P Conclusion: A distinct age-related CBF pattern can be identified with multivariate PCA using ASL MRI.</p

Table_1_The Age-Related Perfusion Pattern Measured With Arterial Spin Labeling MRI in Healthy Subjects.DOCX

<p>Aim: To analyze age-related cerebral blood flow (CBF) using arterial spin labeling (ASL) MRI in healthy subjects with multivariate principal component analysis (PCA).</p><p>Methods: 50 healthy subjects (mean age 45.8 ± 18.5 years, range 21–85) had 3D structural MRI and pseudo-continuous ASL MRI at resting state. The relationship between CBF and age was examined with voxel-based univariate analysis using multiple regression and two-sample t-test (median age 41.8 years as a cut-off). An age-related CBF pattern was identified using multivariate PCA.</p><p>Results: Age correlated negatively with CBF especially anteriorly and in the cerebellum. After adjusting by global value, CBF was relatively decreased with aging in certain regions and relatively increased in others. The age-related CBF pattern showed relative reductions in frontal and parietal areas and cerebellum, and covarying increases in temporal and occipital areas. Subject scores of this pattern correlated negatively with age (R² = 0.588; P < 0.001) and discriminated between the older and younger subgroups (P < 0.001).</p><p>Conclusion: A distinct age-related CBF pattern can be identified with multivariate PCA using ASL MRI.</p

Image_1_The Age-Related Perfusion Pattern Measured With Arterial Spin Labeling MRI in Healthy Subjects.PDF

<p>Aim: To analyze age-related cerebral blood flow (CBF) using arterial spin labeling (ASL) MRI in healthy subjects with multivariate principal component analysis (PCA).</p><p>Methods: 50 healthy subjects (mean age 45.8 ± 18.5 years, range 21–85) had 3D structural MRI and pseudo-continuous ASL MRI at resting state. The relationship between CBF and age was examined with voxel-based univariate analysis using multiple regression and two-sample t-test (median age 41.8 years as a cut-off). An age-related CBF pattern was identified using multivariate PCA.</p><p>Results: Age correlated negatively with CBF especially anteriorly and in the cerebellum. After adjusting by global value, CBF was relatively decreased with aging in certain regions and relatively increased in others. The age-related CBF pattern showed relative reductions in frontal and parietal areas and cerebellum, and covarying increases in temporal and occipital areas. Subject scores of this pattern correlated negatively with age (R² = 0.588; P < 0.001) and discriminated between the older and younger subgroups (P < 0.001).</p><p>Conclusion: A distinct age-related CBF pattern can be identified with multivariate PCA using ASL MRI.</p

Table_2_The Age-Related Perfusion Pattern Measured With Arterial Spin Labeling MRI in Healthy Subjects.DOCX

<p>Aim: To analyze age-related cerebral blood flow (CBF) using arterial spin labeling (ASL) MRI in healthy subjects with multivariate principal component analysis (PCA).</p><p>Methods: 50 healthy subjects (mean age 45.8 ± 18.5 years, range 21–85) had 3D structural MRI and pseudo-continuous ASL MRI at resting state. The relationship between CBF and age was examined with voxel-based univariate analysis using multiple regression and two-sample t-test (median age 41.8 years as a cut-off). An age-related CBF pattern was identified using multivariate PCA.</p><p>Results: Age correlated negatively with CBF especially anteriorly and in the cerebellum. After adjusting by global value, CBF was relatively decreased with aging in certain regions and relatively increased in others. The age-related CBF pattern showed relative reductions in frontal and parietal areas and cerebellum, and covarying increases in temporal and occipital areas. Subject scores of this pattern correlated negatively with age (R² = 0.588; P < 0.001) and discriminated between the older and younger subgroups (P < 0.001).</p><p>Conclusion: A distinct age-related CBF pattern can be identified with multivariate PCA using ASL MRI.</p