MIAMI—The routine clinical diagnostic accuracy for dementia hovers in the 50 to 80 percent range, yet the capability to differentiate Alzheimer’s disease, dementia with Lewy bodies and frontotemporal lobe dementia will be critical as therapeutic treatment strategies are identified. PET imaging with novel radiopharmaceuticals could provide physicians the key they need to unlock the mysteries of various dementias, Kirk A. Frey, MD, PhD, told the audience during the June 10 plenary session at the annual meeting of the Society of Nuclear Medicine and Molecular Imaging (SNMMI).
The annual economic burden of dementia has reached $150 billion, said Frey, who is chief of nuclear medicine at University of Michigan, Ann Arbor, adding that it is expected to triple in the next 20 years. As researchers focus on developing therapeutic interventions to stall or treat dementias, accurate identification of dementia syndrome is needed as interventions targeting amyloid build-up, for example, will be ineffective among patients with non-Alzheimer’s dementias. In addition, while anti-psychotics are contraindicated among patients with some types of dementia they may be effective in others. Finally, Frey noted that advances in disease-modifying therapy will require an understanding of underlying neuropathologies.
All neurodegenerative syndromes are characterized by pathological accumulation of proteins; however, key differences define each syndrome. Definitive diagnosis of Alzheimer’s disease requires histopathological confirmation of amyloid plaques and neurofibrillary tangles.
FDG-PET has revealed some insights into Alzheimer’s disease, showing metabolic features such as cortical glucose hypometabolism and asymmetrical, yet internally consistent, defects. However, a study published Aug. 8, 2006, in Neurology demonstrated the tendency of approximately 10 percent of elderly normal people to have pattern that resembles Alzheimer’s disease. “What does this mean? Is it possible that [these scans] are depicting something else?” asked Frey.
Florbetapir F-18 PET appears to be showing fibrillary amyloid deposition, said Frey, who referred to results published Jan. 11, 2011, in the Journal of the American Medical Association, which correlated florbetapir F-18 PET results with the presence of B-amyloid in the brain at autopsy.
Based on these data, Frey outlined the current working hypothesis regarding Alzheimer’s diagnosis. “Amyloid deposition occurs in the presymptomatic phase and probably relatively rapidly. Thereafter, there may be a mild amyloid gain of 3 to 5 percent. Sometime after that process comes to completion, there is a response in neurons. When this occurs, the patient becomes symptomatic and can be diagnosed with dementia.”
The possibility of frontotemporal dementia complicates the diagnostic process. More than 75 percent of patients with frontotemporal lobe dementia meet the criteria for Alzheimer’s disease. However, an accurate diagnosis is critical as these patients do not benefit from therapy targeting Alzheimer’s disease. “Their behavior may deteriorate with treatment for mild cognitive impairment.” Two other critical differences underscore the need to differentiate patients. “Anti-psychotics are not contraindicated for these patients, and anti-amyloid agents will not benefit patients [with frontotemporal lobe dementia] when these therapies are developed.”
According to a study published Aug. 18, 2007 in Brain, FDG-PET improved diagnostic accuracy and confidence for Alzheimer’s disease and frontotemporal lobe dementia, but did not allow physicians to reliably exclude frontotemporal dementia, said Frey.
Meanwhile, dementia with Lewy bodies resembles Alzheimer’s disease on FDG-PET scans, except the visual cortex is affected in patients with dementia with Lewy bodies. Again, diagnostic accuracy is critical as there may be adverse effects of antipyschotics among patients with dementia with Lewy bodies, while cognition may differentially benefit from AChE (acetylcholinesterase) inhibition.
Frey shared results of a prospective study, published in Brain May 9, 2011, of amyloid and dopamine terminal PET among patients with mild dementia to classify Alzheimer’s disease, frontotemporal lobe dementia and dementia with Lewy bodies.
“We found a number of cases where clinical consensus agreed with the image-based classification, but in more than one-third of cases imaging resulted in a different diagnosis than clinical consensus.”
Frey suggested that the amyloid scan can diagnose dementia with Lewy bodies if that pattern is found. A normal amyloid scan would indicate no dementia. The dopamine terminal scan could subclassify patients with Alzheimer’s disease or frontotemporal lobe dementia.
“This proposed use of amyloid imaging to exclude Alzheimer’s disease versus frontotemporal lobe dementia will be crucial when a therapeutic treatment strategy is identified,” said Frey, who added that longitudinal follow-up is needed to confirm the molecular imaging findings.