title: Divergent neuroprotective effects of nimodipine in PDD and MID provide indirect evidence of disturbances in Ca2+ homeostasis in dementia.
abstract: Evidence suggesting that increased cytotoxic Ca2+ concentrations due to disturbances of Ca2+ homeostasis are involved in neuronal deterioration in dementia has accumulated but has not yet been explicitly confirmed. Here we report of divergent neuroprotective effects of nimodipine, a Ca2+ channel blocker with high lipophilic properties, in primary degenerative dementia (PDD) and multiinfarct dementia (MID). Our clinical data show that nimodipine improves clinical symptomatology and cognitive functions in dementia significantly better than placebo but is more effective in PDD than in MID. This fact becomes explicitly apparent by comparison of the mean value differences of each of the 18 SCAG items between onset and termination of treatment in the two diagnostic groups. The divergent therapeutic response in PDD and MID suggests that the neuroprotective effects of nimodipine can not be due mainly to unspecific cognition enhancing mechanisms or vasodilatation of cerebral blood vessels but must primarily be the consequence of a direct activity in depolarized neuronal cells and of its ability to protect neuronal tissue from Ca2+ overload. Hence, we conclude that disturbances in Ca2+ homeostasis play an important role in the process of neuronal deterioration in dementia. Although we can not entirely rule out the possibility that pharmacological activities besides the modulation of neuronal Ca2+ influx contribute to the effects of nimodipine, from a clinical view our results provide indirect evidence of disturbances in Ca2+ homeostasis as one of the primary factors in the demential process. Our results further support the usefulness of nimodipine in the pharmacotherapy of age-related mental deficits.
authors.affiliation: Psychiatric Hospital of Vienna, Austria.
authors.forename: P K
authors.initials: PK
authors.lastname: Fischhof
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D002118:Calcium / Q000378:metabolism*; D003071:Cognition / Q000187:drug effects; D003704:Dementia / Q000188:drug therapy* / Q000378:metabolism; D015161:Dementia, Multi-Infarct / Q000188:drug therapy* / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D015577:Geriatric Assessment; D006706:Homeostasis; D006801:Humans; D008297:Male; D008875:Middle Aged; D009553:Nimodipine / Q000494:pharmacology / Q000627:therapeutic use*; D016037:Single-Blind Method
chemical_list: D009553:Nimodipine; D002118:Calcium