Neuroimaging in alzheimer’s disease: Relevance for treatment

Abstract

Neuroimaging methodologies have shown some of their greatest promise in studies of Alzheimer's disease (AD). Imaging outcome measures are now entering the arena of investigational trials for AD, to elucidate treatment mechanisms, optimize drug dosing, and perhaps serve as surrogate efficacy measures. Drugs that enhance central cholinergic neurotransmission have been extensively examined for their effects on regional cerebral blood flow, regional cerebral glucose metabolism, or levels of N-acetyl-aspartate in AD patients. Putative disease-modifying agents will be studied by structural magnetic resonance imaging for their ability to reduce rates of hippocampal or whole brain atrophy. When anti-amyloid therapies reach widespread clinical testing, their effects may be monitored by specific imaging probes for amyloid-beta peptide-containing senile plaques. Neuroimaging studies of AD patients and asymptomatic subjects who carry the apolipoprotein E e4 allele suggest that these individuals may be particularly suitable for testing candidate prevention therapies for AD.

Effects of Transcutaneous Electrical Nerve Stimulation (TENS) on Self-Efficacy and Mood in Elderly with Mild Cognitive Impairment

“…69 In AD, APOE ε4 is associated with a reduction in regional cerebral metabolic rate of glucose in, among others, the prefrontal regions. 70 Importantly, although findings are equivocal, APOE ε4 may decrease the effectiveness of specific types of interventions such as tacrine, a cholinesterase inhibitor, and estrogen in AD. 71,72 The possibility that APOE ε4 also hinders the effectiveness of TENS in an MCI population should be examined in future research.…”

Imaging Amyloid-β Deposits In Vivo

“…Indeed, an imaging agent that reflected the amount of either amyloid-␤ or neurofibrillary tangle (NFT) burden, or both, would be advantageous, especially because such a test could be used to evaluate individuals with the earliest stage of the neuropathologic alterations of AD (Arriagada et al, 1992) rather than waiting until behavioral manifestations can be detected. Moreover, a biomarker that closely tracked with the neuropathologic alterations of the disease would be useful for evaluating the efficacy of treatments aimed at reversal or stabilization of lesions directly (van Dyck, 2001). Since current therapeutic trials depend on waiting for several years to determine whether treatment strategies alter the rate of progression of dementia, such an imaging strategy would have the effect of jump-starting the drug discovery process for AD.…”