Differential FDDNP PET Patterns in Nondemented Middle-Aged and Older Adults

Abstract

Objective-We explored whether positron emission tomography (PET) with 2-(1-{6- [(2-[F-18] fluoroethyl)(methyl) amino]-2-naphthyl} ethylidene)malononitrile (FDDNP), a molecule that binds to plaques and tangles in vitro, might identify homogeneous subgroups of persons in middle-aged and older persons with mild cognitive impairment (MCI) or normal cognition. Participants-Fifty-six subjects (MCI, N = 29; normal cognition, N = 27).Measurements-FDDNP-PET scans were performed. Logan parametric images were produced using cerebellum as a reference region, and relative distribution volumes were obtained for regions of interest (ROIs) known to accumulate plaques and tangles in Alzheimer's disease (AD). Cluster analysis was used to identify subgroups of subjects according to FDDNP signal distribution. Once the FDDNP clusters were indentified, we then characterized the clusters also with respect to diagnosis and cognitive test performances and conducted analyses on cluster differences on these variables.Results-We identified three FDDNP clusters: high signal in lateral temporal and posterior cingulate ROIs (high temporal-posterior cingulate HT/PC); low signal in all ROIs (low global cluster, LG); high frontal and parietal signal with intermediate temporal and posterior cingulate signal (HF/ PA). Most MCI subjects belonged to the HT/PC and HF/PA clusters, while most cognitively normal subjects were in the LG cluster. On cognitive tests, the HT/PC and HF/PA clusters performed significantly worse than LG; but did not significantly differ from each other.Conclusions-This approach may be useful in identifying potential high risk imaging cluster patterns. Longitudinal follow-up would be performed to determine the association of these subgroups with diagnostic and functional outcome.Address reprint requests to Linda Ercoli, Semel Institute, 760 Westwood Plaza, Los Angeles, CA, phone (310) 825-9208; Fax (310) 267-0356; lercoli@mednet.ucla.edu. DISCLOSURES The University of California, Los Angeles, owns the U.S. patent (6,274,119) entitled "Methods for Labeling β-Amyloid Plaques and Neurofibrillary Tangles," which has been licensed Siemens. Drs. Small, Huang, Cole, Satyamurthy, and Barrio are among the inventors. Dr. Small reports having served as a consultant and received lecture fees from Abbott, AstraZeneca, Eisai, Forest, Memory Fitness Institute, Novartis, Ortho-McNeil, Pfizer, and Siemens. Dr. Lavretsky reports having received lecture fees from Eisai, Jannsen, and Pfizer and received a research grant from Forrest. Dr. Ercoli reports having received lecture fees from the Memory Fitness Institute, and has also received funds to attend the Larry L. Hillblom Foundation annual meeting to present these and other results. Dr. Barrio reports having served as a consultant and received lecture fees from Nihon Medi-Physics Co, Bristol-Meyer Squibb, PETNet Pharmaceuticals, and Siemens. NIH Public Access Author ManuscriptAm J Geriatr Psychiatry. Author manuscript; available in PMC 2010 June 8. OBJECTIVEEarly detection of Alzh...

Vascular Risk and FDDNP-PET Influence Cognitive Performance

“…The current observation that FDDNP-PET binding levels significantly correlate with cognitive performance in non-demented subjects confirms and extends prior findings from our group [32][33][34]. Using FDDNP-PET, we previously reported cognitive performance in a smaller sample of cognitively normal older adults (n = 10) and found significant correlation between cognitive performance and FDDNP-PET binding levels in frontal and parietal regions [33].…”

Vascular Risk and FDDNP-PET Influence Cognitive Performance

“…The current observation that FDDNP-PET binding levels significantly correlate with cognitive performance in non-demented subjects confirms and extends prior findings from our group [32][33][34]. Using FDDNP-PET, we previously reported cognitive performance in a smaller sample of cognitively normal older adults (n = 10) and found significant correlation between cognitive performance and FDDNP-PET binding levels in frontal and parietal regions [33].…”

Tau in Late-Life Depression: A Systematic Review and Meta-Analysis

“…The posterior cingulate and lateral temporal regions were noted to have significantly higher binding in the MDD group. The authors note that this pattern of [ 18 F]FDDNP binding is similar to that seen in a group of individuals without cognitive impairment [57], and different from the typical AD pattern, which shows binding throughout most of the neocortex, particularly in mesial temporal and parietal regions. Only 1 of the patients with MDD had MCI.…”

Response to Letter From Shin and Lee, Entitled “2-(1-{6-[(2-[Fluorine-18]Fluoroethyl)(Methyl) Amino]-2-Naphthyl} Ethylidene)Malononitrile Positron Emission Tomography Patterns in Nondemented Populations”

“…We appreciate the comments of Dr. Shin and Dr. Lee in response to our recent report describing potential high-risk imaging cluster patterns in FDDNP binding (1), and we wish to clarify that our group's experience with FDDNP imaging is consistent with the important results from Dr. Shin's group pointing to medial temporal FDDNP binding as a potential marker for high-risk subgroups of non-demented individuals (2). In previous analyses of a similar subject group, we found that individuals with mild cognitive impairment who were apolipoprotein E-4 carriers had higher medial temporal binding than non-carriers (3).…”

Vascular Risk and FDDNP-PET Influence Cognitive Performance

“…The current observation that FDDNP-PET binding levels significantly correlate with cognitive performance in non-demented subjects confirms and extends prior findings from our group [32][33][34]. Using FDDNP-PET, we previously reported cognitive performance in a smaller sample of cognitively normal older adults (n = 10) and found significant correlation between cognitive performance and FDDNP-PET binding levels in frontal and parietal regions [33].…”

Tau in Late-Life Depression: A Systematic Review and Meta-Analysis

“…The posterior cingulate and lateral temporal regions were noted to have significantly higher binding in the MDD group. The authors note that this pattern of [ 18 F]FDDNP binding is similar to that seen in a group of individuals without cognitive impairment [57], and different from the typical AD pattern, which shows binding throughout most of the neocortex, particularly in mesial temporal and parietal regions. Only 1 of the patients with MDD had MCI.…”

Response to Letter From Shin and Lee, Entitled “2-(1-{6-[(2-[Fluorine-18]Fluoroethyl)(Methyl) Amino]-2-Naphthyl} Ethylidene)Malononitrile Positron Emission Tomography Patterns in Nondemented Populations”

“…We appreciate the comments of Dr. Shin and Dr. Lee in response to our recent report describing potential high-risk imaging cluster patterns in FDDNP binding (1), and we wish to clarify that our group's experience with FDDNP imaging is consistent with the important results from Dr. Shin's group pointing to medial temporal FDDNP binding as a potential marker for high-risk subgroups of non-demented individuals (2). In previous analyses of a similar subject group, we found that individuals with mild cognitive impairment who were apolipoprotein E-4 carriers had higher medial temporal binding than non-carriers (3).…”

Vascular Risk and FDDNP-PET Influence Cognitive Performance

“…The current observation that FDDNP-PET binding levels significantly correlate with cognitive performance in non-demented subjects confirms and extends prior findings from our group [32][33][34]. Using FDDNP-PET, we previously reported cognitive performance in a smaller sample of cognitively normal older adults (n = 10) and found significant correlation between cognitive performance and FDDNP-PET binding levels in frontal and parietal regions [33].…”

Tau in Late-Life Depression: A Systematic Review and Meta-Analysis

“…The posterior cingulate and lateral temporal regions were noted to have significantly higher binding in the MDD group. The authors note that this pattern of [ 18 F]FDDNP binding is similar to that seen in a group of individuals without cognitive impairment [57], and different from the typical AD pattern, which shows binding throughout most of the neocortex, particularly in mesial temporal and parietal regions. Only 1 of the patients with MDD had MCI.…”

Response to Letter From Shin and Lee, Entitled “2-(1-{6-[(2-[Fluorine-18]Fluoroethyl)(Methyl) Amino]-2-Naphthyl} Ethylidene)Malononitrile Positron Emission Tomography Patterns in Nondemented Populations”

“…We appreciate the comments of Dr. Shin and Dr. Lee in response to our recent report describing potential high-risk imaging cluster patterns in FDDNP binding (1), and we wish to clarify that our group's experience with FDDNP imaging is consistent with the important results from Dr. Shin's group pointing to medial temporal FDDNP binding as a potential marker for high-risk subgroups of non-demented individuals (2). In previous analyses of a similar subject group, we found that individuals with mild cognitive impairment who were apolipoprotein E-4 carriers had higher medial temporal binding than non-carriers (3).…”