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 With ChEI, perfusion improved as did cognition 
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Post With ChEI, perfusion improved as did cognition
"In this study, 11 mild DLB, 16 mild AD and 16 age-matched controls underwent arterial spin-labeled perfusion MRI (ASL-pMRI) and neuropsychological testing. Patterns of cerebral blood flow (CBF) and cognitive performance were compared."

"Frontal and parieto-occipital hypoperfusion was observed in both DLB and AD but was more pronounced in DLB." I'm assuming that "hypoperfusion" refers to low perfusion or low flow of blood in these parts of the brain.

A further test was performed on some of the DLB study participants; they were given a "pharmacologic MRI." The MRI was performed when a medication -- Aricept, a cholinesterase inhibitor -- was administered to patients. In this case, the ChEI was given to four of the DLB study participants. "Following ChEI treatment, perfusion increased in temporal and parieto-occipital cortex, and cognitive performance improved on a verbal fluency task." So, it seems that a change in the cholinergic system resulted in increased cerebral blood flow and this resulted in improved cognitive performance!

"If confirmed in a larger study, these results provide further evidence for brain cholinergic dysfunction in DLB pathophysiology, and use of pharmacologic MRI as an in vivo measure of cholinergic function."

I wondered how "mild" was defined so I skimmed the article for that information. For many dementia researchers, disease severity is based upon MMSE scores. I thought that "mild" meant an MMSE score of 22-24. In this study, the "mild" DLB participants had MMSE scores of about 28 while the "mild" AD participants had MMSE scores of about 25.

The authors admit that a limitation of this study is that "the DLB and AD groups differed in MMSE scores." Further, while "MMSE is often used as a measure of disease severity in AD, it has not been validated in DLB. In addition, matching based on MMSE score is likely flawed due to differences in cognitive domains affected in DLB and AD, as methods which place more weight on orientation, attention, and construction aspects from the MMSE may be more sensitive for differentiating DLB from AD. However, even without accurate matching on disease severity, the finding of greater hypoperfusion in DLB compared to AD despite a 'normal' performance on MMSE remains a clinically important finding."

There are at least two additional shortcomings with this study. First, the numbers of study participants are very small. Second, there is no pathological confirmation of the diagnoses. Diagnostic accuracy for AD is quite high but for DLB is quite low (less than 33%).

I've copied the abstract below.

Robin



Brain Imaging and Behavior. 2010 Oct 6. [Epub ahead of print]

Association cortex hypoperfusion in mild dementia with Lewy bodies: a potential indicator of cholinergic dysfunction?

Fong TG, Inouye SK, Dai W, Press DZ, Alsop DC.
Aging Brain Center, Institute for Aging Research, Hebrew SeniorLife, Boston, MA.

Abstract
Dementia with Lewy bodies (DLB) is often associated with occipital hypometabolism or hypoperfusion, as well as deficits in cholinergic neurotransmission.

In this study, 11 mild DLB, 16 mild AD and 16 age-matched controls underwent arterial spin-labeled perfusion MRI (ASL-pMRI) and neuropsychological testing. Patterns of cerebral blood flow (CBF) and cognitive performance were compared.

In addition, combined ASL-pMRI and ChEI drug challenge (pharmacologic MRI) was tested as a probe of cholinergic function in 4 of the DLB participants. Frontal and parieto-occipital hypoperfusion was observed in both DLB and AD but was more pronounced in DLB. Following ChEI treatment, perfusion increased in temporal and parieto-occipital cortex, and cognitive performance improved on a verbal fluency task.

If confirmed in a larger study, these results provide further evidence for brain cholinergic dysfunction in DLB pathophysiology, and use of pharmacologic MRI as an in vivo measure of cholinergic function.

PubMed ID#: 20924800 (see pubmed.gov for this abstract only)


Thu Oct 07, 2010 9:35 pm
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