Dementia of the Alzheimer’s type

Other nootropic agents in some stage of clinical development include nebracetam (9), nefinacetam (10), and BMY 21502 (11). Nebracetam, an aminomethyl pyrrolidinone derivative, is expected to be approved in Japan in 1994 (73). In clinical studies involving patients having cerebrovascular or senile dementia of the Alzheimer s type, clinical symptoms such as spontaneous or emotional expression were enhanced in up to 71% of cases. Long-term treatment using nebracetam in patients with cerebral infarction also afforded marked improvement in most cases with few side effects (74). A review of this compound has beenpubUshed (75). 

AD is the most common type of dementia, affecting approximately 4.5 million Americans in the year 2000.2 Table 32-2 lists the different classifications of dementia.3 This chapter will address only dementia of the Alzheimer s type. 

Dementia of the Alzheimer s type (early- or late-onset)... 

The ChE inhibitors all have the indication for the treatment of mild to moderate dementia of the Alzheimer s type. Guidelines for the treatment of AD were written before the approval of memantine and recommend the use of ChE inhibitors as a valuable treatment for AD.27-29 None of the ChE inhibitors have been compared in head-to-head studies, so the decision to use one over another is based on differences in mechanisms of action, adverse reactions, and titration schedules. 

Donepezil is approved for the treatment of mild to moderate dementia of the Alzheimer s type at a dose of 5 mg/day. This dose should be increased to 10 mg/day if needed after 4 to 6 weeks. Table 32-5 describes the dosing strategies for all of the approved agents for Alzheimer s disease.34-38... 

The first neurochemical evidence of a disturbed serotonin function in cognition came from the changes in serotonin and/or 5-hydroxyindoleacetic acid (5-HIAA) levels in a number of forebrain nuclei, the temporal and cingulate cortex, hippocampus, and other areas of the brain taken at autopsy from patients with senile dementia of the Alzheimer s type (Adolfsson et al. 1978 Arai et al. 1984 D. M. Bowen et al. 1979, 1983 A. J. Cross et al. 1983 Winblad et al. 1982). The depletions are regionally selective reductions in se-... 

Similar results were obtained from material taken from patients with senile dementia of the Alzheimer s type (Chan-Palay et al. 1992). A loss of tryptophan hydroxylase immunoreactive neurons in the raphe nuclei, which was most pronounced in the lateral division, was correlated with both age and cortical pathology. Furthermore, tyrosine hydroxylase reactive neurons were also found to be reduced in the locus coeruleus, even more so than the tryptophan hydroxylase reactive neurons. The same was also found for material taken from brains with Parkinson s disease. 

Nemeroff CB, Krishnan KRR, Reed D, et al Adrenal gland enlargement in major depression a computed tomographic study. Arch Gen Psychiatry 49 384-387, 1992 Nestler EJ, Terwilliger RZ, Duman RS Chronic antidepressant administration alters the subcellular distribution of cyclic AMP-dependent protein kinase in rat frontal cortex. J Neurochem 53 1644-1647, 1989 Nestor PC, Parasuraman R, Haxby JV, et al Divided attention and metabolic brain dysfunction in mild dementia of the Alzheimer s type. Neuropsychologia 29(5) 379-387, 1991... 

Prince DA, Wilder BJ Cortical mechanisms in cortical epileptogenic foci surrounded inhibition. Arch Neurol 16 194-202, 1967 Prinz PN, Vitahano PP, Vitiello MV, et al Sleep, EEC and mental function changes in senile dementia of the Alzheimer s type. Neurobiol Aging 3 361-370, 1982... 

Memantine is currently the only medication approved by the FDA for the treatment of moderate to severe dementia of the Alzheimer s type (Reisberg et al. 2003 Winblad and Poritis 1999). Although its use also has been investigated in patients with mild to moderate vascular dementia (Orgogozo et al. 2002 Wilcock et al. 2002), this specific use has not yet been approved. 

Persistent excitatory glutamatergic stimulation of postsynaptic NMDA receptors, which may cause neuronal toxicity by allowing excessive calcium entry into neurons, has been implicated in the symptomatology of dementia of the Alzheimer s type (Farber et al. 1998). Memantine is a moderate-affinity, noncompetitive inhibitor of NMDA receptors (Danysz et al. 2000). 

Chatellier G, Lacomblez L Tacrine (tetrahydroaminoacridine THA) and lecithin in senile dementia of the Alzheimer s type a multicentre trial. Groupe Fran(jais d Etude de la Tetrahydroaminoacridine. BMJ 300 495-499, 1990... 

The Molecular and Cellular Pathogenesis of Dementia of the Alzheimer s Type An Overview... 

Bergman J, Brettholz I, Shneidman M, Lerner V. Donepezil as add-on treatment of psychotic symptoms in patients with dementia of the Alzheimer s type. Clin Neuropharmacol 2003 26 88-92. 

In a prospective randomized, double blind, parallel-group, multicenter comparison of idebenone 360 mg/day (n = 104) and tacrine up to 160 mg/day (n — 99) for 60 weeks in 203 patients with mild-to-moderate dementia of the Alzheimer s type, idebenone produced more benefit than tacrine (2). The benefit harm balance was favorable for idebenone compared with tacrine. More patients taking tacrine (65%) reported adverse events than those... 

Indications Mild dementia of the Alzheimer s type Category Cholinesterase inhibitor Half-life 50-70 hours... 

AD is the most common cause of dementia, accounting for over 60% of cases of late-life cognitive dysfunction. Table 63-1 lists etiology-based subclasses of dementia. This chapter focuses exclusively on dementia of the Alzheimer s type. However, the reader is encouraged... 

Geldmacher DS, Waldman AJ, Doty L, Heilman KM. Fluoxetine in dementia of the Alzheimer s type Prominent adverse effects and failure to improve cognition. J Clin Psychiatry 1994 55 161. 

Corvea, M. (1987, Fall). Senile dementia of the Alzheimer s type and multiinfarct dementia A clinical comparison. Rorida State University. 

---