Secondary Alzheimer's disease: Characteristics of Alzheimer's disease preceded by non-alzheimer’s pathology


      A negative amyloid PET scan is inconsistent with a neuropathological diagnosis of Alzheimer’s disease at the time of image acquisition, however it does not guarantee to escape Alzheimer’s disease in the future. We often observe multiple-pathology in the neuropathological examination in the autopsy series of dementias in elderly-elders. Our hypothesis is that an existence of certain non-Alzheimer type neurodegenerative disorder can induce and/or accelerates amyloid pathology to develop a “secondary” Alzheimer’s disease. To test this hypothesis, we examine the longitudinal amyloid deposition in amyloid negative subjects with progressive cognitive declines.


      We studied 15 PiB negative patients with progressive cognitive decline, including 10 MCI subjects and five dementia patients. Annual follow up of PiB-PET scan was performed for three years. The PiB-PET images acquired 50-70 min post injection were co-registered to individual MRI data of same visit, and automated VOI analysis were performed using DARTEL template, standard set of volumes of interest, and cerebrospinal fluid volume correction. The mean cortical uptake (mcSUVR) was calculated as the average of composite VOIs. We set the cut off level of mcSUVR for PiB positivity at 1.5.


      In the follow up observation, 3 MCI subjects and 2 dementia patients turned out to be PiB positive. The averaged annual rate of mcSUVR increase in those subjects was 4.9%. It was significantly higher than the averaged annual increase rate of 2.3% in PiB positive MCI and AD in our previous study. The FDG-PET images of those incidental PiB positive subjects initially showed non-AD type hypometabolism, but overlapped by AD type hypometabolism after PiB positive conversion.


      Our results suggest that non-Alzheimer neurodegeneration may induce “secondary” Alzheimer’s disease with more rapid progression than sporadic cases. Further studies are required in larger sample size longer observation to clarify the details of overlapping pathology.
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