There is increasing evidence of a vascular contribution to Alzheimer's disease (AD). In some cases, prior work suggests that chronic brain hypoperfusion could play a prime pathogenic role contributing to the accumulation of amyloid-β,while other studies favor the hypothesis that vascular dysfunction and amyloid pathology are independent, although synergistic, mechanisms contributing to cognitive impairment. Vascular dysfunction can be evaluated by assessing cerebral blood flow impairment. Phase contrast velocity mapping by MRI offers a non-invasive means of quantifying the total inflow of blood to the brain. This quantitative parameter could be a sensitive indicator of vascular disease at early stages of AD. In this work, phase contrast MRI was used to evaluate cerebral hemodynamics in patients with subjective memory complaints, amnestic mild cognitive impairment, and mild to moderate AD, and compare them with control subjects. Results showed that blood flow and velocity were decreased in the patients with cognitive dysfunction and the decrease correlated with the degree of cognitive impairment as assessed by means of neuropsychological tests. Total cerebral blood flow measurements were clearly reduced in AD patients, but more importantly appeared to be sensitive enough to distinguish between healthy subjects and those with mild cognitive impairment. A quantitative measurement of total brain blood flow could potentially predict vascular dysfunction and compromised brain perfusion in early stages of AD.

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Oxodipine, a new calcium channel blocker, induced gingival hyperplasia in rats. This is the first time that a calcium channel blocker has been documented as resulting in gingival hyperplasia in rats. In contrast to diphenylhydantoin, the hyperplastic changes induced by oxodipine were not precipitated by any prior irritation. The histology consisted of purely fibroblastic proliferation without infiltrate of inflammatory cells.

Subchronic oral exposure of dogs to Oxodipine, a new calcium channel blocker of the dihydropyridine-type, resulted in dose-related gingival hyperplastic changes. The doses at which an effect was elicited were 24 and 73 times the intended therapeutic dose for man. The effects were first noted after 7 weeks of treatment, and were limited to the high and intermediate dose groups of both sexes. Macroscopically, a generalized enlargement of the maxillary and mandibular facial and lingual gingivae were noted. The histological changes were similar to those described in man for Nifedipine and hydantoin-related drugs. An increase in the activity of alkaline phosphatase and a decrease in alanine aminotransferase was demonstrated. This article is the first to describe gingival hyperplasia in dogs induced in a dose-dependent manner by a calcium channel blocker.

The constipatory effects of oxodipine, a dihyrdopyridine-type calcium antagonist, have been described in a 3-mo, 12-mo, and 30-mo feeding toxicity study in rats. This paper reports the occurrence of megacolon in rats as a result of the constipatory effects of chronic administration of oxodipine. The first mortality due to oxodipine was seen after about 1 yr of treatment at a dose of 225 mg/kg/day. The toxic effects noted were dose-, time-, and sex-related. Female rats appeared more sensitive to the constipatory effects of the drug.The dose at which the effect occurred in both male and female rats was from about 75 to 675 times the recommended therapeutic dose for humans. To the best knowledge of the authors, this is the first report of a calcium channel blocker causing constipation in rats.