Study: PET may improve dementia diagnosis for Down syndrome

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Known to be significantly more susceptible to dementia, individuals with Down syndrome appear to display age-related increases in amyloid senile plaques and tau neurofibrillary tangles that mirror those increases in Alzheimer’s patients as viewed with PET, according to a study published in the June issue of Archives of Neurology.

Down syndrome has been associated with a high likelihood of developing dementia among individuals older than 45 years, markedly earlier than the general population. Autopsies have revealed that these persons with Down syndrome display heightened cortical deposits of amyloid senile plaques (SP) and tau neurofibrillary tangles (NFT), indistinguishable from the same hallmarks observed in the progression of Alzheimer’s disease.

In the present study, researchers investigated whether this same pattern can likewise be seen among those with Down syndrome at earlier ages. SP and NFT loads were measured using PET with the ligand 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile, or [F-18]FDDNP.

The study consisted of three groups: a healthy control group of 10 persons with a mean age of 44, 10 Alzheimer’s patients with a mean age of 67 years and 19 individuals with Down syndrome and a mean age of 37. All PET images were reconstructed using filtered back projection (FBP) with measured attenuation correction and were corrected for scatter.

The Down syndrome group showed significantly higher binding levels of [F-18]FDDNP than controls in all regions of interest, as well as higher values globally and in the parietal and frontal lobes compared with Alzheimer’s patients.

The researchers also observed significant associations between age and [F-18]FDDNP binding values in the parietal, lateral temporal and frontal regions, as well as globally. These findings were consistent with SP and NFT accumulation patterns observed in autopsy studies.

No significant binding level differences were found in the posterior cingulate, medial temporal or lateral temporal regions between the Down syndrome and Alzheimer’s disease groups. Likewise, an association was not observed between age and the Cognitive and Social Scales of the Dementia Questionnaire for Mentally Retarded Persons.

“Of interest was the observation that non-demented subjects with Down syndrome showed higher [F-18]FDDNP binding compared with Alzheimer’s disease subjects, globally and in the parietal and frontal lobes. This observation could reflect the early and extensive accumulation of SP and NFT deposits in Down syndrome,” explained Linda D. Nelson, PhD, and co-authors from the University of California, Los Angeles (UCLA).

The study’s small sample size and head motion during scanning marked the study’s major limitations, the authors said.

“Given the considerable challenges in diagnosing dementia in people with Down syndrome using cognitive and behavioral measures, neuroimaging may offer added clinical value,” Nelson and colleagues concluded.