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Extra info for Central Nervous System Diseases
The implication has beenthat degeneration of cholinergic neurons in this brain region in AD must not contribute to any of the impairments that characterize the disease. Do Basal Forebrain ChoIinergicNeurons Play a Role in A D Memory Deficits? Do the lesion data truly demonstrate that loss of basal forebrain cholinergic neurons in AD play no role in the cognitive deficits associated with the disease, as some (4) have suggested. Although these lesion data, alone, do not permit a definitive answer, the weight of all the evidence, considered collectively, does not easily support that conclusion.
Moreover, individual patients are typically either arbitrarily assigned to a particular dose, or else are tested to establish their maximum tolerat dose (rather than peak efficacious dose). This is especially puzzling because a detail meta-analysis performed more than a decade ago concluded that “cholinergic enhanc ment of memory function in AD showed that such therapies do have an effect if dm ages are individualized’ (158, p. 237, emphasis added). , 159,160). Some have attempted to link the identity of the subgroups to gene markers (such as apoE4 alleles) (161), whereas others have suggested that more pr saic pharmacokinetic/ bioavailability reasons exist (162,163).
The Challengeof Using Aged Rodents to Model Age-Related Memo y Impairments Although studies of aged rodent memory have played important roles advancing biogerontology, and in elucidating many neurological mechanisms responsible for agerelated behavioral deficits (106-1 I]), their role in the development of cholinergic strategies and specific treatments is less clear (except perhaps for confirming the in vivo cholinergic activity of certain lead compounds). When one looks at the nature of the work done with aged rodents, the reasons for this become more evident.