Single photon emission computed tomography with [99Tc]-HM-PAO and [123I]-IBZM in Alzheimer's disease and dementia of frontal type: preliminary results

Abstract

Dementia of frontal type (DFT) is a fairly common degenerative disease distinct from Alzheimer's disease (AD), whose reportedly distinctive instrumental feature is frontal lobe hypoperfusion on SPECT. We evaluated the cortical dopaminergic system in 6 AD, 5 DFT, and 6 control subjects with SPECT and both [99Tc]‐HM‐PAO, a perfusion tracer, and [123I]‐IBZM, a D2 postsynaptic ligand. Both in AD and DFT patients, [99Tc]‐HM‐PAO SPECT showed a relative frontal hypoperfusion. On the contrary, [123I]‐IBZM SPECT showed significantly reduced ligand uptake in superior frontal regions of DFT (0.89 ± 0.08 relative to control subjects) as compared to AD patients (0.97 ± 0.02; difference of means: 0.08, 95% Confidence Interval 0.004 to 0.156; p = 0.041). Results suggest more marked involvement of the frontal cortical dopaminergic system in DFT than in AD patients.

Differentiation of frontotemporal dementia from dementia with Lewy bodies using FP-CIT SPECT

“…Other evidence of dopamine dysregulation in FTD includes lower CSF levels of homovanillic acid (a metabolite of dopamine) and dopamine,41 and reduced dopamine D2 receptor ligand uptake in the frontal cortex 42. As yet, it is not known why EPMS occurs in FTD or what the extent of striatal dysfunction is, but the negative correlation observed between an EPMS and dopamine uptake supports a causal relationship 25.…”

Reward processing in neurodegenerative disease

“…These vulnerable regions and functional networks include structures in common with the known anatomy of the reward system, suggesting that patients with bvFTD may have abnormalities in reward processing underlying some of their change in behavior. The changes could also be neurochemical as well as structural, but the evidence of dopamine deficiency in bvFTD has been mixed, with some finding deficiency (Frisoni et al, 1994; Rinne et al, 2002) and others not (Francis et al, 1993; Sjogren, Wikkelso, Ostling, Wallin, & Blennow, 2002). …”

Management of Frontotemporal Dementia: Targeting Symptom Management in Such a Heterogeneous Disease Requires a Wide Range of Therapeutic Options

“…Much evidence exists to support the contention that not only frontal and temporal lobe systems are defunct in FTD, but also that specific neurotransmitter systems are dysregulated in these conditions (Table 3). Cholinergic [71–76], dopaminergic [77–81], GABAergic [72,82], glutamatergic [72,82], noradrenergic [72,80,81] and serotonergic [73,83–85] system involvement have all been implicated in the development of the signs and symptoms of FTD. As such, modulation of such key pathways and neurotransmitter systems may play a central role in our understanding of currently available therapeutic options for FTD.…”

“…Still, undisputed efficacy in AD suggests that memantine may still have a role in the therapeutic armament for FTD if underlying AD pathology is suspected. While further studies are needed to clarify direction and magnitude of effects of these agents, a wealth of clinical and biological data support the use of such agents in empiric attempts to alleviate symptoms in FTD [3,71–77,89–92,94,110,111]. Other small-scale studies and case reports have suggested that such agents may have significant psychiatric and behavioral effects that may negate their utility in some patients with FTD because symptoms worsen rather than abate with their use [89,93].…”