Alzheimer Disease: Algotsson A

Algotsson A, Winblad B. · Department of Clinical Neuroscience, Occupational Therapy and Elderly Care Research, Division of Geriatric Medicine, Karolinska Institute, Huddinge University Hospital, Huddinge, Sweden. · Dement Geriatr Cogn Disord. · Pubmed #14739530 No free full text.

Abstract: In epidemiological, cross-sectional studies, treatment with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) prevented to a large extent the development of Alzheimer's disease (AD), but the results of randomized, placebo-controlled studies, focused on statin therapy in patients with ischemic heart disease (IHD), are at variance. Nonetheless, data from epidemiological, longitudinal studies in humans as well as studies on transgenic mouse models and cultured neuronal cell lines indicate that cholesterol may contribute to the pathogenesis of AD. Statins have proven therapeutic and preventive effects in IHD and other vascular diseases in man. They generally are well tolerated, but some adverse effects, probably due to antiproliferative and proapoptotic properties of the statins, are matters of concern. AD patients may be extrasusceptible to adverse effects of statins due to preexisting aberrations in signal transduction and energy metabolism in the neurons and a perturbed cholesterol metabolism in the brain. This problem might be addressed in randomized, double-blind studies with statins in AD. The statins differ from each other in several aspects, and they are not considered to be therapeutically interchangeable. It could be fruitful to use both a placebo and two different types of statins, i.e. an essentially hydrophilic statin and a lipophilic statin, in a double-blinded fashion, and to compare the effects on the cognitive decline in AD.

Algotsson A, Winblad B. · Division of Clinical Geriatrics, Department of Neurobiology, Caring Sciences and Society, Karolinska Institutet, Karolinska University Hospital, SE-141 86 Huddinge, Sweden. · Acta Neurol Scand. · Pubmed #17511849 No free full text.

Abstract: OBJECTIVE: To evaluate the integrity of the blood-brain barrier (BBB) in incident Alzheimer's disease (AD). MATERIALS AND METHODS: The mean age of the 157 patients (45% men) was 69.7(9.4) years (range 51-88 years). The patients had undergone a thorough investigation including magnetic resonance imaging or computed tomography of the brain. The cerebrospinal(CSF)/plasma albumin ratio (albumin ratio) was used as a measure of BBB function. RESULTS: There were gender differences with respect to albumin ratio and plasma creatinine with higher values in men (P < 0.001). 42% of the men and 13% of the women (P < 0.001) had a mild to moderate BBB dysfunction when applying the reference limit of the laboratory (<9.2). Both male gender (P = 0.002) and plasma creatinine (P = 0.009) were independently associated with the albumin ratio when controlling for putative confounders. CONCLUSIONS: The BBB is dysfunctional in a portion of patients with AD, both women and, primarily, men. The dysfunction might influence the clearance of both harmful and beneficial substances across the barrier. Renal function might have an impact on the BBB.