From: olivercranglejr@gmail.com   
      
   Loss of Smell Linked to Brain Abnormality, Transition to AD   
   Susan Jeffrey   
   July 14, 2014   
       
   COPENHAGEN, Denmark -- Two new studies link impaired olfactory function to   
   elevated brain amyloid and greater neurodegeneration in cognitively normal   
   adults, as well as progression to Alzheimer's disease (AD), among patients   
   with mild cognitive    
   impairment (MCI).   
      
   The findings suggest testing olfactory function may be a useful screening   
   biomarker in the diagnostic work-up for AD in patients at risk for dementia,   
   researchers say.   
      
   The new results, from the Harvard Aging Brain Study and the North Manhattan   
   Study, were presented here at the Alzheimer's Association International   
   Conference (AAIC) 2014.   
      
   Amyloid Deposition, Neurodegeneration   
      
   Previous research has shown that regions of the brain that process odor input,   
   including the olfactory bulb and entorhinal cortex, are particularly   
   susceptible to AD pathology, and are affected at early stages of the disease,   
   lead author Matthew E.    
   Growdon, MA, an MD/MPH candidate at Harvard Medical School and Harvard School   
   of Public Health, Boston, Massachusetts, pointed out.   
      
   "Building on this, there has been interest in the field to develop clinical   
   tests of odor identification," Growdon said. "Most notably, the one we're   
   talking about today is the University of Pennsylvania Smell Identification   
   Test, or UPSIT [Sensonics Inc]   
   , which is a very low-cost, easy-to-administer, 40-item scratch-and-sniff test   
   that can be used easily in the clinic."   
      
      
   Matthew E. Growdon   
   In 1 study, Growdon and colleagues looked at whether there was an association   
   between olfaction, memory performance, and biomarkers of neurodegeneration and   
   amyloid deposition in clinically normal individuals participating in the   
   Harvard Aging Brain    
   Study. The sample includes 215 community-dwelling individuals aged 64 to 88   
   years, who undergo annual testing, including comprehensive neuropsychological   
   testing, hippocampal volume and entorhinal cortex thickness -- both structures   
   important for memory    
   and both measured using MRI -- and amyloid burden using Pittsburgh Compound B   
   positron emission tomography (PET).   
      
   He stressed that this analysis is entirely cross-sectional at this point,   
   looking at associations at the beginning of the study. "We're hoping to   
   reanalyze as we go forward longitudinally, but I'd like to emphasize we're   
   just looking at a snapshot in    
   time."   
      
   Among all the individuals in their study, smaller entorhinal cortex and   
   hippocampal size were associated with worse odor identification using the   
   UPSIT tool, and worse memory. "These were statistically significant and modest   
   effects," Growdon noted.   
      
   When they looked at amyloid PET findings, they found that among participants   
   with higher amounts of amyloid deposition in their brain, a smaller entorhinal   
   cortex was similarly associated with a worse UPSIT score (P = .03 for   
   interaction). "That suggests    
   at least in this small dataset that there seems to be an interplay between the   
   size of the subjects' brains and the amount of amyloid that they have," he   
   noted.   
      
   In future, they hope to further study olfactory testing as a screening   
   modality in 3 groups of these patients: those who did poorly just on the odor   
   identification (lower 25th percentile for the UPSIT test, upper 75th   
   percentile for the memory testing,    
   28% of the total patients); those who did poorly just on the memory testing   
   (upper 75th percentile for the UPSIT test, lower 25th percentile for memory   
   testing, 9% of the total patients) and those who did poorly on both tests   
   (lower 25th percentile for    
   UPSIT and memory testing, 16% of patients).   
      
   "This is a hypothesis at this point, but we would like to follow all 3 of   
   those groups over the next 5 years at least, and see who might be at higher   
   risk of developing cognitive symptoms," he said.   
      
   "I think what's interesting here in this cross-sectional study is finding   
   significant associations between a relatively simple, low-cost tool like the   
   University of Pennsylvania Smell Identification Test and these more   
   established but costly and at times    
   invasive biomarkers like the PET scan, and the size of the brain on MRI scan,"   
   Growdon said. "I think we can say there is potentially a role for something   
   like the [UPSIT] in clinically normal, asymptomatic older individuals, and I   
   envision it as    
   something that could flag those who are at risk for developing Alzheimer's   
   disease symptoms, or potentially as a gateway to more expensive or invasive   
   procedures like a spinal tap or a PET scan, so it could be part of a whole   
   panel of testing."   
      
   Still, he said, it's not yet "ready for prime time," and more longitudinal   
   follow-up is required to confirm that poor olfactory performance does   
   translate to higher AD risk. "So I find it very intriguing, but I'm also   
   cautious at this point about its    
   role as a screening tool."   
      
   Transition from MCI to AD   
      
      
   Dr. Devangere Devanand   
   In a separate study, Devangere Devanand, MBBS, MD, professor of psychiatry and   
   neurology at Columbia University Medical Center, New York, New York, presented   
   results using the UPSIT in a group of participants in the North Manhattan   
   Study, an ongoing    
   epidemiologic study of a multiethnic community sample.   
      
   "The olfactory bulb and tract are affected earliest in Alzheimer's disease; in   
   brains going to pathology; in some cases it looks as if maybe even earlier   
   than the entorhinal cortex and the hippocampus, which is why we looked at it,"   
   Dr. Devanand pointed    
   out. He distinguished between odor sensitivity and detection, which is not   
   affected in AD, and odor identification, which is the aspect affected by the   
   disease, possibly because it requires an element of interpreting or "testing"   
   the odor against a    
   stored memory.   
      
   The UPSIT odor identification testing was added to the North Manhattan Study   
   evaluation during 2004 to 2006; this report looks at 2 subsequent evaluations,   
   at 2 years (2006 to 2008) and 4 years (2008 to 2010). The majority of   
   participants were women (69%)   
   , the mean age was 80.5 years, there was a fairly even distribution of the 3   
   major ethnic groups in the United States: white, African American, and   
   Hispanic.   
      
      
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