Alzheimer Disease: Crisby M

Crisby M, Carlson LA, Winblad B. · The Alzheimer Disease Research Center, Karolinska Institute, Neurotec Division of Geriatric Medicine, Huddinge University Hospital, Stockholm, Sweden. · Alzheimer Dis Assoc Disord. · Pubmed #12218642 No free full text.

Abstract: Vascular risk factors such as hypertension and hypercholesterolemia during midlife increase the risk for Alzheimer's disease (AD). Treatment of hypercholesterolemia and other vascular risk factors may have great implications in the prevention of AD. Recent findings illustrate that the sterol metabolism in the brain is an active process, well controlled and regulated by 24-hydroxylase, an enzyme that is uniquely expressed in the brain. The use of statins in ischemic heart disease (IHD) has proven to be a phenomenal advance in pharmacological disease prevention and treatment. A growing body of evidence, suggest that statins exhibit additional benefits that are independent of their cholesterol-lowering actions. Statin treatment has also considerable effect in prevention of ischemic stroke. In animal models of ischemic stroke, statins have proven to reduce infarct size through up-regulation of endothelial nitric oxide synthases. Data from recent observational studies have revealed a potential role for statins in prevention of AD. The following review comments the processes leading to dementia including the involvement of cholesterol regulation, cerebral circulation and inflammation in development of dementia. The mechanisms by which statins may be beneficial in controlling these processes is discussed.

van der Flier WM, van Straaten EC, Barkhof F, Verdelho A, Madureira S, Pantoni L, Inzitari D, Erkinjuntti T, Crisby M, Waldemar G, Schmidt R, Fazekas F, Scheltens P. · Alzheimer Center, Department of Neurology, Vrije Universiteit Medical Center, Amsterdam, The Netherlands. · Stroke. · Pubmed #16141425 links to  free full text

Abstract: BACKGROUND AND PURPOSE: On cerebral magnetic resonance imaging (MRI), white matter hyperintensities (WMH) and lacunes are generally viewed as evidence of small vessel disease. The clinical significance of small vessel disease in terms of global cognitive function has as yet not been completely clarified. We investigated the independent contribution of WMH and lacunes to general cognitive function in a group of independently living elderly with varying degrees of small vessel disease. METHODS: Data were drawn from the multicenter, multinational Leukokraurosis and Disability (LADIS) study. There were 633 independently living participants. General cognitive function was assessed using the Mini Mental State Examination (MMSE) and the modified Alzheimer Disease Assessment Scale (ADAS). On MRI, WMH was rated as mild, moderate, or severe. Lacunes were rated as none, few (1 to 3), or many (4 or more). RESULTS: In the basic analysis, increasing severity of both WMH and lacunes was related to deteriorating score on the MMSE and ADAS. When WMH and lacunes were entered simultaneously, both MRI measures remained significantly associated with MMSE score. Increasing severity of WMH remained associated with ADAS score, whereas the association with lacunes became less prominent. These associations were independent of other risk factors for dementia, like education, depression, vascular risk factors, or stroke. CONCLUSIONS: We found WMH and lacunes to be independently associated with general cognitive function in a sample of independently living elderly. These results highlight the fact that WMH and lacunes should both be evaluated when assessing small vessel disease in relation to cognitive function.

Bretillon L, Sidén A, Wahlund LO, Lütjohann D, Minthon L, Crisby M, Hillert J, Groth CG, Diczfalusy U, Björkhem I. · Division of Clinical Chemistry, Karolinska Institutet, Huddinge University Hospital, Huddinge, SE-141 86, Stockholm, Sweden. · Neurosci Lett. · Pubmed #11027840 No free full text.

Abstract: The brain is the exclusive or almost exclusive site of formation of 24S-hydroxycholesterol and we have shown that the circulating level of 24S-hydroxycholesterol is dependent upon the relation between cerebral production and hepatic clearance. In the present work we determined plasma levels of 24S-hydroxycholesterol in patients with various neurological diseases. Eleven subjects with brain death occurring 6-10 h before collection of the plasma samples had markedly reduced circulating levels of 24S-hydroxycholesterol (-43%, P<0.001). Patients with advanced Alzheimer's disease and cerebral inflammatory diseases had slightly lower levels of 24S-hydroxycholesterol in plasma when compared to matched controls. Patients with acute ischemic stroke, multiple sclerosis and primary brain tumors had levels not significantly different from those of controls. The conditions leading to reduced plasma levels of 24S-hydroxycholesterol had no significant effect on plasma levels of another side-chain oxidized oxysterol, 27-hydroxycholesterol. Except for conditions characterized by very marked destruction of the central nervous system, different severe neurological diseases seem to have relatively small effects on the flux of 24S-hydroxycholesterol from the brain.