Our principal local research interest involves neuroimaging in AD and healthy aging. We have worked primarily with single photon emission computed tomography (SPECT) and positron emission tomography (PET), utilizing both neuroreceptor ligands and tracers of regional cerebral blood flow (rCBF).
Dopamine Transporter (DAT) Imaging
Dr. van Dyck and colleagues have conducted a series of investigations of the nigrostriatal dopamine system using the DAT radioligand [123I]ß-CIT and SPECT. Our contribution to this research has emphasized studies of healthy aging, but has also included the effects of sex and menstrual cycle (Best et al, 2005), DAT genotype (van Dyck et al, 2005), and a number of clinical disorders (e.g., adult Attention Deficit Hyperactivity Disorder—van Dyck et al, 2002a). Our aging studies of the DAT have demonstrated that over the normal adult lifespan striatal DAT availability—as a marker of nigrostriatal terminals—declines by about 50% (van Dyck et al, 1995), at a rate that is approximately linear and with a pattern of striatal subregions and hemispheric asymmetry that differs from that of Parkinson’s disease (van Dyck et al, 2002b).
Most recently (van Dyck et al, 2007 in press), we have begun to examine the functional significance of nigrostriatal dopaminergic degeneration in normal aging—which has heretofore been uncertain. In a study of 36 healthy elderly subjects, we have demonstrated that striatal DAT availability is correlated with reaction speed but not with several comparison tasks. This research has provided some of the first human evidence of a relationship between nigrostriatal dopaminergic function and a behavioral measure in normal aging. It specifically suggests that the motoric slowing of aging—with its consequences for daily functioning—is related to the degeneration of the brain's nigrostriatal dopamine system. Our results have laid the groundwork for development of drug treatments and other intervention strategies for the elderly.
Other Studies of Neuroreceptor Imaging
In addition, we have conducted studies of the central serotonin transporter (SERT) using [123I]ß-CIT and SPECT (Neurobiol Aging, 2000;21:497-501), the 5HT2A receptor using [18F]deuteroaltanserin and PET (J Nucl Med, 2000;41:234-241. Nucl Med Biol, 2000;27:715-722), and studies of the a4ß2 nicotinic receptor using the SPECT ligand [123I]5-I-A-85380.
Studies of Regional Cerebral Blood Flow (rCBF) in AD
SPECT studies or regional cerebral blood flow (rCBF) have shown among their greatest promise as diagnostic and research tools in AD. Our previous rCBF SPECT studies have compared the diagnostic utility of different rCBF tracers in AD (J Nucl Med 1996;37:1749-1755) and have examined the effects of an experimental cholinergic therapy (linopirdine) on rCBF deficits in AD (Junior Investigator Award, American Association for Geriatric Psychiatry; Psychopharmacology 1997;132:217-226). Linopirdine treatment was found to "reverse" 24% of the baseline parietal perfusion deficit in the AD patients. These data support the conclusion that rCBF abnormalities in AD are, in part, truly “functional" and can be selectively altered with pharmacological interventions. The parietal activation seen with linopirdine, in conjunction with other convergent evidence, suggests that, in the development of cholinergic drug therapies for AD, greater utilization should be made of tasks subserved by the parietal lobes. We have also completed a study of the effect of the Apolipoprotein E e4 (ApoE e4) allele on the pattern of SPECT rCBF in AD (Arch Neurology 1998;55:1460-1466). This work has demonstrated significantly greater parietal rCBF asymmetry in the ApoE e4– patients than the ApoE e4+ patients. If replicated, this study suggests that ApoE e4– AD may be associated with other (as yet undiscovered) genetic or environmental risk factors which confer greater neuropathological asymmetry.
Finally, in addition to our participation in NIH consortia for AD treatments, we are also a key site for the NIH Alzheimer’s Disease Neuroimaging Initiative (ADNI) consortium, which is performing MRI and PET scans in patients with mild AD and MCI, and healthy elderly subjects.