This study demonstrates that impairment on a neuropsychological measure of visual constructive ability is strongly correlated with the degree of gray matter loss in the right inferior temporal gyrus, and not with other measures of hippocampal, regional, or global cortical atrophy, in a group of patients with probable AD. All patients showed evidence of hippocampal and generalized cortical atrophy, irrespective of the degree of right inferotemporal atrophy. Moreover, a group of patients with AD who performed significantly worse than other patients with AD on the visual constructive task showed significantly more atrophy of the right inferior temporal gyrus, but not other brain structures. These findings suggest that atrophy of the right inferior temporal gyrus may serve as a neuroimaging marker of visual constructive impairment in patients with AD.
Copying a complex two-dimensional figure requires neural processes related to visual perception, working memory, executive control, and motor sequencing. As such, damage to multiple brain regions could theoretically produce deficits on such a task. Thus, it was striking that atrophy of a single neuroanatomic region, the right inferior temporal gyrus, was correlated with this deficit in patients with probable AD. Atrophy of this region was not correlated with design fluency performance. This finding may reflect a different cognitive demand in the design fluency task, because the task requires a subject to generate new shapes as opposed to copying shapes. The generation of novel designs is in part dependent on executive function, which is likely to have different anatomic correlates in the frontal lobes.
These results are consistent with earlier cross-sectional and longitudinal FDG-PET and structural MRI studies that demonstrated asymmetric cortical hypometabolism12,30
in patients with probable AD. A previous SPECT study showed relative hypoperfusion of the right parietotemporal region in some patients with AD with impaired performance on the Rey copy,32
and an analysis of sulcal variability in patients with AD demonstrated significant correlations between right temporoparietal atrophy and visuospatial impairment.9
We have extended these results by providing a more detailed localization of a specific visual constructive deficit.
Nonhuman primate studies have demonstrated that the activity of neurons in a cortical region that is homologous to the right inferior temporal gyrus, the inferotemporal cortex, is increased when the animal is asked to process low dimensional configurations of two-dimensional shapes.33
This suggests that the selective atrophy of this region in our patients may have led to difficulty in creating a mental representation of the image that was to be copied. A recent atrophy-corrected fMRI study of an angle discrimination task demonstrated an increase in blood oxygen level dependent signal in the same cortical region in patients with AD relative to controls,34
suggesting that neuronal activity may be increased in this region during such tasks. Whether this increased activity represents a compensatory mechanism or reflects an activity-dependent neurodegenerative mechanism is unclear.
Focal cortical atrophy is most commonly associated with atypical or early onset presentations of AD, such as the syndromes of posterior cortical atrophy,10
primary progressive aphasia,35
and the frontal lobe variant of AD.6
Prominent cortical atrophy, sometimes in the absence of hippocampal atrophy, is readily appreciable on MRI scans in these patients.36
Here it is demonstrated that typical patients with AD, all of whom were initially evaluated for memory or word-finding difficulties, may also display regional cortical atrophy that is measurable while the patients are still alive. If these measurements were repeated in a population of incipient AD patients with isolated visuospatial impairment,13
this pattern of atrophy might be detectable in the absence of hippocampal atrophy.
Cortical atrophy is highly correlated with histopathologic markers of AD, and accounts for a significant proportion of premortem cognitive deficits in clinical-pathologic correlations of patients with definite AD.3
The results presented here show that measurements of well-defined cortical regions of interest may improve the clinical relevance of structural MRI-based measurements in AD. In future longitudinal studies of AD, it will be of interest to correlate the change in atrophy of the right inferior temporal gyrus with changes in performance on neuropsychological measures of visual constructive ability.