Regional Cerebral Perfusion Alterations in Patients with Mild Cognitive Impairment and Alzheimer Disease Using Dynamic Susceptibility Contrast MRI

Rationale and Objectives

The purpose of this study was to assess regional cerebral perfusion distribution in patients with Alzheimer disease (AD) or mild cognitive impairment (MCI) using dynamic susceptibility contrast magnetic resonance imaging.

Materials and Methods

Regional changes of perfusion were evaluated in 34 patients with AD, 51 patients with MCI, and 23 healthy controls (HCs). Using region of interest analyses, regional cerebral blood flow (CBF), cerebral blood volume, and mean transit time were measured bilaterally in the hippocampus; the temporal, temporoparietal, frontal, and sensomotoric cortices; the anterior and posterior cingulate gyri; the lentiform nucleus; and the cerebellum.

Results

A significant reduction of CBF in patients with AD compared to HCs was shown in the frontal and temporoparietal cortices bilaterally, the lentiform nuclei bilaterally, the left posterior cingulate gyrus, and the cerebellum. Compared with patients with MCI, patients with AD presented a reduction of CBF in the frontal cortices bilaterally, the left temporoparietal cortex, and the left anterior and posterior cingulate gyrus. In both hippocampi and the posterior cingulate gyrus, a trend to a slight increase of CBF in patients with MCI was noticed with a decrease in patients with AD.

Conclusions

Using dynamic susceptibility contrast magnetic resonance imaging, pathologic alterations of regional brain perfusion can be demonstrated in patients with AD compared to patients with MCI or HCs.

Dementing disorders are the most frequent neuropsychiatric diseases of the elderly population. In about two thirds of subjects with dementia, the dementia is related to Alzheimer disease (AD) . AD has an insidious onset and progresses in a time-frame of years with decline in a broad range of neuropsychological domains such as memory, executive functions and attention, language, and apraxia. In AD, the progressive degeneration of the brain is, on the one hand, caused by changes in tau protein, which lead to destabilization of the cytoskeleton . On the other hand, increased creation of β-amyloid and its accumulation into amyloid plaques lead to an inflammatory and oxidative-toxic processes . Both processes result in an irreversible damage of neuronal cells. Beside the deposition of amyloid in the brain parenchyma in AD, a perivascular amyloid accumulation is present in most cases . Thus, small-vessel alterations are obvious, resulting in altered cerebral blood flow (CBF). In addition, reduced CBF and the resulting reduced elimination of amyloid may amplify further accumulation of amyloid in perivascular regions and the brain parenchyma itself, with both situations worsening the dementing disorder .

The preclinical phase of AD is characterized by mild cognitive deficits that exceed physiologic age-related cognitive decline. However, they are not as severe as in subjects with a confirmed dementing disorder. Clinical and epidemiologic evidence indicate that this preliminary stage, called mild cognitive impairment (MCI), remains subtle over a long phase before the threshold of dementia is reached . It is assumed that MCI is associated with a substantially increased risk of AD . The early diagnosis of AD and the exclusion of secondary causes of dementia are essential for optimized therapeutic management of patients.

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Materials and methods

Subjects

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Clinical Evaluation

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MRI

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Morphologic MR images

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DSC-MRI

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Analysis and Postprocessing

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Statistics

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Results

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Table 1

Region of Interest Values of Cerebral Blood Glow ∗

Region of Interest HCs Patients with MCI Patients with AD_F_ Test_n_ mean ± SD_n_ mean ± SD_n_ mean ± SD_P_ Cerebellum 19 63.9 ± 32.2 46 52.4 ± 27.7 34 43.6 ± 19.7 † .028 Right hippocampus 21 49.9 ± 24.6 50 51.2 ± 25.8 34 43.1 ± 24.1 .334 Left hippocampus 21 50.4 ± 24.8 51 52.6 ± 29.5 34 47.0 ± 22.2 .637 Right temporal cortex 22 63.2 ± 39.6 51 56.3 ± 29.2 34 44.6 ± 21.5 .056 Left temporal cortex 22 56.1 ± 34.0 50 51.0 ± 27.7 34 40.7 ± 18.4 .081 Right temporoparietal cortex 22 69.0 ± 35.6 51 60.1 ± 31.8 34 48.6 ± 22.0 † .042 Left temporoparietal cortex 22 68.0 ± 35.8 50 58.7 ± 27.8 33 46.0 ± 19.1 †,‡ .013 Right lentiform nucleus 21 58.7 ± 32.8 50 44.5 ± 24.8 34 36.6 ± 18.1 † .007 Left lentiform nucleus 21 60.2 ± 33.7 50 47.3 ± 26.0 34 38.9 ± 19.7 † .015 Right anterior cingulate gyrus 18 49.2 ± 24.2 43 48.9 ± 24.4 28 36.0 ± 19.2 .051 Left anterior cingulate gyrus 18 46.2 ± 25.0 43 48.3 ± 24.1 28 34.9 ± 17.0 ‡ .044 Right posterior cingulate gyrus 18 52.4 ± 28.9 43 55.0 ± 31.0 28 39.2 ± 16.9 .052 Left posterior cingulate gyrus 18 51.6 ± 28.0 43 53.5 ± 30.8 28 35.7 ± 15.7 †,‡ .020 Right frontal cortex 22 59.8 ± 33.3 51 51.5 ± 28.7 34 39.7 ± 16.1 †,‡ .018 Left frontal cortex 22 60.6 ± 35.0 51 50.3 ± 28.2 34 39.2 ± 15.1 †,‡ .014 Right sensomotoric cortex 13 47.3 ± 30.6 38 47.1 ± 24.2 25 35.2 ± 19.2 .131 Left sensomotoric cortex 13 44.8 ± 29.0 38 47.7 ± 27.0 25 34.3 ± 18.6 .113

n , number of patients; SD, standard deviation; HC, healthy control; MCI, mild cognitive impairment; AD, Alzheimer disease.

Post-hoc t tests were calculated to test for significant group differences.

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Discussion

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Comparison of CBF Values in Patients with AD and HCs

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Comparison of CBF Values in Patients with MCI and HCs

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Comparison of CBF Values in Patients with AD or MCI

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CBV Analyses

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MTT Analyses

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Limitations

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Conclusions

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Acknowledgments

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