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DOI: 10.1055/s-2005-919213
Cerebral perfusion is globally reduced in Alzheimer's disease – The missing link?
Regional cerebral blood flow (rCBF) is reportedly reduced in brain areas affected by the Alzheimer disease (AD) histopathology, such as beta-amyloid plaques and neurofibrillary tangles (NFT), in particular temporal and parietal cortex. Therefore, reduced rCBF was usually interpreted as a consequence of lost neuronal activity caused by neurodegeneration. However, so far, such rCBF measurements were done by single photon emission computed (SPECT) or positron emission (PET) tomography with relative values of activity referring to overall global means or reference regions such as cerebellum within individuals.
Methods: We examined 10 patients with mild to moderate AD and 10 age-matched healthy control subjects (HCS) (Tab1) with full quantitative 15O-water-PET scans. All patients and probands had diagnostic neuropsychology and MRI examinations. For quantification of blood flow data all participants had an arterial line. Results were compared in regions of intrest (ROI), including cortical regions (frontal, parietal, temporal), thalamus, striatum and cerebellum.
Results: We report here, for the first time, full quantitative rCBF measurements done by 15O-water-PET demonstrating markedly and globally reduced rCBF in all brain regions of mild to moderate AD patients as compared to age-matched healthy controls (Figure), including such areas as cerebellum and striatum which are known to be unaffected by the AD histopathology. Lowered rCBF exceeded by far the areas typically loaded with beta-amyloid plaques and NFTs and was evident in absence of any MRI signs for vascular encephalopathy. Blood flow was stronger reduced in cortical regions (parietal 58% of HCS, temporal 61% and frontal 67%) than in cerebellum (74% of HCS) or striatum (76% of HCS).
Conclusion: Our results point to a general dysfunction of neurovascular coupling and include the possibility of a major role of reduced blood flow in the pathophysiology of AD.
|
Table 1 |
|
HCS |
AD |
|
N |
|
10 |
10 |
|
Age (yr |
|
70.9±5.8 |
69.6±5.3 |
|
Female |
|
6 |
6 |
|
Male |
|
4 |
4 |
|
MMSE |
|
29.3±0.8 |
20.3±3.5 |
|
AD history1 |
|
NA |
17 (0–38) |
|
ChEI therapy |
|
0 |
8 |
|
-duration1 |
|
NA |
17.3 (5–29) |
|
Memantine |
|
0 |
2 |
|
-duration1 |
|
NA |
2/6 |
|
ApoEε |
2/3 |
3 |
1 |
|
p=0.009 |
3/3 |
3 |
1 |
|
|
2/4 |
2 |
2 |
|
|
3/4 |
2 |
2 |
|
|
4/4 |
0 |
4 |
|
1Time in month (range) |
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