Article Figures & Data
Figures
- Fig 1.
Hippocampal volume in patients with MCI versus controls. Hippocampal volume is calculated as the total volume of the right and left hippocampus and regressed on ICV. The standardized residuals are shown on the y-axis (z-scores). The patients are grouped according to whether they have pathologic (MCI pat CSF) or nonpathologic (MCI no CSF) values of tau or Aβ42. The blue-dotted lines indicate the mean value for each group. Independent samples t tests (Bonferroni corrected for multiple comparisons) showed that the patients with pathologic CSF biomarkers had significantly smaller hippocampal volume than the controls, whereas the other contrasts did not reach significance.
- Fig 2.
Effects of diagnosis on cortical thickness. Points where patients with MCI have a significantly thinner cortex than normal controls are color coded as blue-green, whereas points showing the opposite pattern are coded as red-yellow. The P maps are projected onto the inflated mean brain of the total sample. From left to right is shown the right and left lateral view, and left and right medial view, respectively.
- Fig 3.
Scatterplots of cortical thickness in patients versus controls. ROIs were chosen on the basis of the results from the cortical thickness comparisons. The ROIs are defined by the red lines. Mean thickness for each participant within each ROI was calculated.
- Fig 4.
Distribution of P values. This figure shows the number of voxels for any given P value from the cortical comparisons illustrated in Fig 2. The left side of each chart (blue-green colors) represents a thicker cortex in healthy controls; the right side (red-yellow colors) represents a thicker cortex in the patients. As can be seen, the distribution of P values is shifted to the left, with almost no voxels to the right of the midline (indicating thicker cortex for patients). This shows clearly that the patients have a thinner cortex than the healthy controls and that it is very unlikely that this is a result of false-positives from multiple statistical comparisons.
- Fig 5.
Relationships between tau pathologic features and brain morphometry. Hippocampal volume and mean thickness in left hemisphere entorhinal ROI compared across groups of pathologic (pato) versus nonpathologic (norm) T-tau or P-tau values.
- Fig 6.
Relationships between cortical thickness and episodic memory. Hippocampal volume/mean thickness in left hemisphere ROIs from Fig 3 and RAVLT learning and 30 minutes delayed recall score. The y-axes depict the number of words recalled, whereas the x-axes depict thickness or ICV-corrected volume.
Tables
Controls MCI Sample 1 MCI Sample 2 P (SD) (SD) (SD) N 18 18 19 Women/Men 7/11 7/11 10/9 .63 Age (43–77 y) 63.7 (6.3) 61.6 (9.0) 61.8 (7.1) .66 Education 10.8 (2.7) 13.1 (3.3) 11.6 (2.7) .06 GDS NA 2.94 (0.24) 2.95 (0.23) .97 MMSE (23–30) NA 27.4 (1.9) 27.9 (1.7) .47 Symptom duration NA 2.11 (1.40) 2.98 (1.57) .95 Note:—MCI indicates mild cognitive impairment; GDS, Global Deterioration Scale; MMSE, Mini-Mental State Examination.
* The Pvalues are from an ANOVA with a group factor of 3 levels. Post hoc analyses confirmed that none of the contrast between the groups was significant. The MMSE was not administered to the controls. SD is presented in parentheses where relevant.
MCI Sample 1 MCI Sample 2 P N N Aβ42 (pathologic/not pathologic) 3/14 3/16 .89 Tau (pathologic/not pathologic) 7/10 6/13 .56 Any CSF pathologic features (pathologic/not pathologic) 8/9 7/12 .55 APOE ε4 alleles (0/1/2) 8/6/4 10/6/3 .58 Note:—MCI indicates mild cognitive impairment; Aβ42, amyloid beta 42 peptide; APOE ε4, apolipoprotein E.
P denotes the P values from an independent samples t test.
Tau Aβ42 APOE F R F S1 S2 S1 S2 S1 S2 Hippocampus 5.90†‡ 7.86† .30 .51†‡ 0.04 3.19 A: Middle temporal LH 5.57† 0.00 .20 .11 1.24 0.16 B: Inferior parietal LH 1.50 16.67†‡ −.04 .11 0.87 2.60 C: Entorhinal LH 2.32 7.35† .05 .57†‡ 0.42 4.39† D: Precuneus (toward isthmus) LH 1.42 1.06 −.16 .51†‡ 0.98 2.99 E: Superior frontal LH 3.41 1.72 −.08 .24 0.06 1.93 A: Middle temporal RH 1.06 0.77 −.19 .27 0.08 1.47 B: Inferior parietal RH 2.24 10.30†‡ −.11 .29 0.76 0.90 C: Entorhinal RH 1.35 11.32†‡ −.19 .23 0.27 3.62† D: Precuneus (toward isthmus) RH 0.50 3.80 −.25 .59†‡ 1.15 3.85† E: Superior frontal RH 0.00 0.31 −.06 .11 0.51 1.24 Note:—S1 indicates Sample 1; S2, Sample 2; LH, left hemisphere; RH, right hemisphere; Aβ42, amyloid beta 42 peptide; APOE, apolipoprotein E; F, F-ratio; R, Pearson r.
* The effects of the APOE genotype and pathologic values of CSF biomarkers tau and Aβ42 on the morphometry (thickness or volume) of the brain in regions that are significantly different between healthy controls and patients with MCI. Because only 3 participants had pathologic Aβ42 values in each sample, the absolute Aβ42 values were used instead of cutoff values, and the relationships were tested with Pearson correlations. In the rest of the analyses, ANOVA was used. Hippocampus is the sum of the left and right hippocampus, regressed on intracranial volume, and the residuals are used in the analyses. The capital letters refer to the cortical ROI from Fig 3.
† P < .05.
‡ P < .05 when the effect of age is controlled for.
RAVLT Learning* RAVLT 30 Minutes’ Recall R R S1 S2 S1 S2 Hippocampus .49§ .70†‡ .35 .71†‡ A: Middle temporal LH .51† .38 .33 .22 B: Inferior parietal LH .67† .44§ .48‡ .53† C: Entorhinal LH .66† .64†‡ .46 .64†‡ D: Precuneus (toward isthmus) LH .50† .48† .15 .44† E: Superior frontal LH .43 .42 .24 .38 A: Middle temporal RH .49§ .34 .16 .39† B: Inferior parietal RH .56† .49† .53† .60† C: Entorhinal RH .35 .50† .23 .53† D: Precuneus (toward isthmus) RH .28 .54† .04 .54† E: Superior frontal RH .38 .36 .29 .22 Tau −.28 −.60† −.09 −.73†‡ Aβ42 .09 .42 .33 .35 APOE −.09 −.17 −.34 −.18 Note:—S1 indicates Sample 1; S2, Sample 2; RAVLT, Rey Auditory-Verbal Test; APOE, apolipoprotein E; Aβ42; amyloid beta 42 peptide; LH, left hemisphere; RH, right hemisphere; R, Pearson r.
* RAVLT learning is the sum of correct responses across learning trials 1 to 5. APOE is quantified as the number of ε4 alleles (0, 1, or 2). For tau, cutoff criteria are used in the analyses (0 for nonpathologic, 1 for pathologic), whereas for Aβ42 the actual values are used because only 2 participants in Sample 1 had pathologic values.
† P < .05.
‡ P < .05 when the effect of age is controlled for.
§ P < .06.
In this issue
Jump to section
Related Articles
Cited By...
- White matter integrity and cognition in Parkinson's disease: a cross-sectional study
- Biomarker validation of a cued recall memory deficit in prodromal Alzheimer disease
- CSF Biomarkers in Prediction of Cerebral and Clinical Change in Mild Cognitive Impairment and Alzheimer's Disease
- Combining MR Imaging, Positron-Emission Tomography, and CSF Biomarkers in the Diagnosis and Prognosis of Alzheimer Disease
- One-Year Brain Atrophy Evident in Healthy Aging
- Minute Effects of Sex on the Aging Brain: A Multisample Magnetic Resonance Imaging Study of Healthy Aging and Alzheimer's Disease