Atrophy over 1 and 2 years: Continuous surface analyses
The statistical significance of 1 and 2 year volume changes in cortex across the brain surface is shown in . As can be seen, large cortical areas decreased significantly over 1 year. These reductions were most prominent in the temporal lobe, the medial part of the superior frontal gyrus, orbitofrontal, precuneus, supramarginal and inferior parietal, as well as the inferior and part of the middle frontal cortex. Lateral parts of the superior frontal cortex, as well as pre- and post-central gyrus, superior parietal areas, occipital cortex and lingual gyrus were largely spared. Over two years, the effects were stronger and spread to additional areas, involving all cortical areas except lingual cortex and pre- and postcentral gyrus.
Cortical atrophy in healthy elderly
Percentage volume change in cortex over 1 and 2 years is shown in . Annual atrophy rates varied across the cortex, but were typically around 0.5 % in affected areas, including most of the lateral and inferior parts of the temporal lobes, supramarginal gyrus, inferior parietal gyrus, precuneus, inferior and middle frontal gyrus as well as the medial parts of the superior frontal gyrus. Atrophy over 2 years exceeded 1.0 % in large areas.
Rate of change in healthy elderly and AD patients
For comparison purposes, rate of atrophy is presented for AD patients in . Atrophy in the AD group was much larger than in the healthy elderly, with most areas showing 1% annual change or more. This was especially evident in the lateral temporal cortex and an area around posterior cingulate/ inferior precuneus/ retrosplenial cortex (> 2.5% annual change). Less atrophy was seen around the central sulcus, pericalcarine sulcus and lingual gyrus. To compare the pattern of atrophy between the healthy controls and the AD patients, mean cortical atrophy was calculated for each hemisphere in each group. This value was subtracted from the surface maps, yielding a new map highlighting areas that show greater and lesser rates of atrophy than average for that group. These maps illustrate the parts of the cortex that show relatively higher and relatively lower rates of atrophy within each group (). Within the AD group, higher than average atrophy was seen in the inferior and middle temporal gyrus. Within the healthy elderly group, higher than average atrophy was observed in the same areas, but also in the temporal pole, medial orbitofrontal, rostral middle frontal and supramarginal cortex, as well as parts of the medial superior frontal gyrus. Less than average atrophy was seen in cuneus, pericalcarine sulcus, lingual gyrus as well as the central sulcus. Results of formal statistical tests of differences in rates of atrophy between healthy controls and AD patients are described below.
Regional rates of atrophy relative to mean atrophy within group for healthy elderly and AD
Atrophy over 1 and 2 years: ROI analyses
Percentage annual volume change in each of the 48 ROIs is shown in for healthy elderly. Median atrophy for 1 year was −0.38 %, not including the ventricular ROIs. Hippocampus (−0.84 %) and amygdala (−0.81 %) showed the largest reductions, followed by thalamus (−0.69 %). Cerebellum grey matter (−0.35 %), the brain stem (−0.31 %) and caudate nucleus (−0.24 %) showed the least 1 year change of the volumetric ROIs. The inferior lateral (5.47 %), lateral (4.40 %) and the 3rd (3.07 %) ventricles showed the largest changes overall, with no significant change in the 4th (0.71 %) ventricle. Of the cortical ROIs, the frontal pole (−0.59 %), temporal pole (−0.56 %), banks of the superior temporal sulcus (−.55 %), and entorhinal cortex (−0.55 %) changed the most, while post central, pericalcarine, lingual, cuneus and precentral were well preserved (≤ 0.1 %).
Percentage volume change over 1 and 2 years in healthy elderly n.s. indicates p ≥ .01
For comparison purposes, 1 year volume change in each ROI was calculated for the AD group also (). All ROIs except the pericalcarine sulcus showed significant change. Median atrophy for 1 year was −1.20 %, not including the ventricular ROIs. Amygdala (−3.79 %) and hippocampus (−3.75 %) largest reductions, followed by inferior and middle temporal gyri (−2.97 and −2.87%, respectively). Also entorhinal and parahippocampal cortex showed well above average atrophy (−2.42 and −2.05%, respectively). Pericalcarine (−0.16%), postcentral (−0.27%) and cuneus (−0.5%) were the three ROIs showing the least atrophy, but of these only pericalcarine did not change at p < .01 (p = .030). The inferior lateral (16.26 %), lateral (10.35 %) and the 3rd (6.82 %) ventricles showed the largest changes overall.
Percentage volume change over 1 year in the AD group n.s. indicates p ≥ .01
Differences in rates of atrophy were formally tested between healthy elderly and AD patients. AD patients had significantly (p < .01) higher rates of change than the healthy elderly for all ROIs except 4th
ventricle (Supplementary Table 1
). In terms of t-scores, inferior temporal (t = 13.25), fusiform (t = 13.15) and middle temporal (t = 12.81), parahippocampal (t = 12.69) and entorhinal (t = 11.93) showed the largest effects of the cortical ROIs, while hippocampus (t = 12.80), the inferior lateral ventricles (t = 9.74) and amygdala (t = 8.32) showed the largest effects for the volumetric ROIs.
Interaction between the groups and temporal vs. frontal atrophy rates were tested by ANOVA with two groups (healthy elderly, AD) × two brain regions (frontal, temporal). A highly significant interaction was found (F [1, 256] = 119.78, p < 10−22), caused by a higher rate of temporal than frontal atrophy in the AD group and a comparable rate of temporal vs. frontal atrophy rate in the healthy elderly ().
Effects of age on regional atrophy rates
Correlation analyses between age and 1 year atrophy in each of the ROIs were performed. The results are presented in and scatterplots for selected structures in . We focus here on the 1 year changes, since the statistical power was lower for 2 years. Significant correlations between age and rates of atrophy were found for 32 ROIs. For the volumetric structures, hippocampus, cerebellum grey and white matter, cerebral white matter, thalamus and pallidum atrophy were related to age, as was expansion of the inferior lateral ventricles. Of the cortical structures, regions demonstrating significant relationships between age and rate of atrophy included entorhinal, transverse temporal, pars opercularis, isthmus cingulate, middle temporal, pars triangularis, banks of the superior temporal sulcus, parahippocampal, superior temporal, posterior cingulate, caudal middle frontal, precentral, fusiform, inferior parietal, temporal pole, precuneus, supramarginal, lateral orbitofrontal, superior parietal, post central, caudal anterior cingulate, medial orbitofrontal, pericalcarine, lateral occipital and inferior temporal cortices.
Table 4 Pearson correlations between age and 1-year volume change in healthy elderly Negative correlations between age and rate of atrophy, and positive correlations between age and rate of ventricular expansion are generally found, showing that increasing age (more ...)
Relationships between age and rate of atrophy in healthy elderly