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FDG-PET strongest independent predictor of Alzheimer's dementia in MCI

SAN DIEGO – PET imaging with 18-fluorodeoxyglucose is the strongest individual positive predictive biomarker of short-term incident dementia in mild cognitive impairment in the most current iterations of Alzheimer’s disease diagnostic criteria, results from a multicenter analysis of 73 patients suggest.

"Since this was a relatively small population of patients, future studies are needed to confirm the results and to assess the incremental diagnostic value and cost-benefit ratio," Dr. Giovanni Frisoni said at the annual meeting of the American Academy of Neurology.

Dr. Giovanni Frisoni

Dr. Frisoni, of the National Alzheimer’s Center in Brescia, Italy, and his associates conducted a secondary analysis of 73 patients with mild cognitive impairment (MCI) who were treated at clinics in Brescia, Amsterdam, and Stockholm, in an effort to compare the prognostic accuracy of individual criterions in the two current diagnostic criteria for short- to mid-term incident Alzheimer’s dementia in patients with MCI: those published by an International Working Group (IWG) in 2007 and those published in 2011 by the National Institute on Aging and the Alzheimer’s Association (NIA-AA).

The patients were followed for an average of 39 months (at least 1 year for all). They had a mean age of 66 years, and 57% were women. The investigators obtained data on biomarkers of amyloidosis (abnormal amyloid-beta-42 [A-beta-42] in cerebrospinal fluid) and neurodegeneration (hippocampal atrophy on MRI measured with FreeSurfer software, temporo-parietal hypometabolism measured with 18-fluorodeoxyglucose [18-FDG]-PET, and abnormal tau protein levels in cerebrospinal fluid).

"This is a pretty rare group of patients," Dr. Frisoni said.

The researchers then compared positive and negative likelihood ratios of individual items in the IWG and NIA-AA criteria. Dr. Frisoni reported that during the follow-up period, 29 of the patients progressed to Alzheimer’s disease and 44 remained stable. Among IWG criteria, positivity to any biomarker had the lowest negative likelihood ratio (0.00) for Alzheimer’s disease, while positivity to 18-FDG-PET had the highest positive likelihood ratio (5.82) and a low negative likelihood ratio (0.24).

Among NIA-AA criteria, positivity to neurodegeneration as measured by 18-FDG-PET, MRI, or cerebrospinal fluid tau markers, regardless of amyloidosis status, had the lowest negative likelihood ratio (0.06), while positivity to A-beta-42 and 18-FDG-PET or A-beta-42 and hippocampal atrophy had the highest positive likelihood ratios (6.45 and 5.56, respectively).

The study was supported by the Swedish Research Council and by a grant from the Italian Ministry of Health. Dr. Frisoni disclosed that he has received personal compensation for activities with Eli Lilly, Bristol-Myers Squibb, Bayer, and several other companies.

dbrunk@frontlinemedcom.com

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SAN DIEGO – PET imaging with 18-fluorodeoxyglucose is the strongest individual positive predictive biomarker of short-term incident dementia in mild cognitive impairment in the most current iterations of Alzheimer’s disease diagnostic criteria, results from a multicenter analysis of 73 patients suggest.

"Since this was a relatively small population of patients, future studies are needed to confirm the results and to assess the incremental diagnostic value and cost-benefit ratio," Dr. Giovanni Frisoni said at the annual meeting of the American Academy of Neurology.

Dr. Giovanni Frisoni

Dr. Frisoni, of the National Alzheimer’s Center in Brescia, Italy, and his associates conducted a secondary analysis of 73 patients with mild cognitive impairment (MCI) who were treated at clinics in Brescia, Amsterdam, and Stockholm, in an effort to compare the prognostic accuracy of individual criterions in the two current diagnostic criteria for short- to mid-term incident Alzheimer’s dementia in patients with MCI: those published by an International Working Group (IWG) in 2007 and those published in 2011 by the National Institute on Aging and the Alzheimer’s Association (NIA-AA).

The patients were followed for an average of 39 months (at least 1 year for all). They had a mean age of 66 years, and 57% were women. The investigators obtained data on biomarkers of amyloidosis (abnormal amyloid-beta-42 [A-beta-42] in cerebrospinal fluid) and neurodegeneration (hippocampal atrophy on MRI measured with FreeSurfer software, temporo-parietal hypometabolism measured with 18-fluorodeoxyglucose [18-FDG]-PET, and abnormal tau protein levels in cerebrospinal fluid).

"This is a pretty rare group of patients," Dr. Frisoni said.

The researchers then compared positive and negative likelihood ratios of individual items in the IWG and NIA-AA criteria. Dr. Frisoni reported that during the follow-up period, 29 of the patients progressed to Alzheimer’s disease and 44 remained stable. Among IWG criteria, positivity to any biomarker had the lowest negative likelihood ratio (0.00) for Alzheimer’s disease, while positivity to 18-FDG-PET had the highest positive likelihood ratio (5.82) and a low negative likelihood ratio (0.24).

Among NIA-AA criteria, positivity to neurodegeneration as measured by 18-FDG-PET, MRI, or cerebrospinal fluid tau markers, regardless of amyloidosis status, had the lowest negative likelihood ratio (0.06), while positivity to A-beta-42 and 18-FDG-PET or A-beta-42 and hippocampal atrophy had the highest positive likelihood ratios (6.45 and 5.56, respectively).

The study was supported by the Swedish Research Council and by a grant from the Italian Ministry of Health. Dr. Frisoni disclosed that he has received personal compensation for activities with Eli Lilly, Bristol-Myers Squibb, Bayer, and several other companies.

dbrunk@frontlinemedcom.com

SAN DIEGO – PET imaging with 18-fluorodeoxyglucose is the strongest individual positive predictive biomarker of short-term incident dementia in mild cognitive impairment in the most current iterations of Alzheimer’s disease diagnostic criteria, results from a multicenter analysis of 73 patients suggest.

"Since this was a relatively small population of patients, future studies are needed to confirm the results and to assess the incremental diagnostic value and cost-benefit ratio," Dr. Giovanni Frisoni said at the annual meeting of the American Academy of Neurology.

Dr. Giovanni Frisoni

Dr. Frisoni, of the National Alzheimer’s Center in Brescia, Italy, and his associates conducted a secondary analysis of 73 patients with mild cognitive impairment (MCI) who were treated at clinics in Brescia, Amsterdam, and Stockholm, in an effort to compare the prognostic accuracy of individual criterions in the two current diagnostic criteria for short- to mid-term incident Alzheimer’s dementia in patients with MCI: those published by an International Working Group (IWG) in 2007 and those published in 2011 by the National Institute on Aging and the Alzheimer’s Association (NIA-AA).

The patients were followed for an average of 39 months (at least 1 year for all). They had a mean age of 66 years, and 57% were women. The investigators obtained data on biomarkers of amyloidosis (abnormal amyloid-beta-42 [A-beta-42] in cerebrospinal fluid) and neurodegeneration (hippocampal atrophy on MRI measured with FreeSurfer software, temporo-parietal hypometabolism measured with 18-fluorodeoxyglucose [18-FDG]-PET, and abnormal tau protein levels in cerebrospinal fluid).

"This is a pretty rare group of patients," Dr. Frisoni said.

The researchers then compared positive and negative likelihood ratios of individual items in the IWG and NIA-AA criteria. Dr. Frisoni reported that during the follow-up period, 29 of the patients progressed to Alzheimer’s disease and 44 remained stable. Among IWG criteria, positivity to any biomarker had the lowest negative likelihood ratio (0.00) for Alzheimer’s disease, while positivity to 18-FDG-PET had the highest positive likelihood ratio (5.82) and a low negative likelihood ratio (0.24).

Among NIA-AA criteria, positivity to neurodegeneration as measured by 18-FDG-PET, MRI, or cerebrospinal fluid tau markers, regardless of amyloidosis status, had the lowest negative likelihood ratio (0.06), while positivity to A-beta-42 and 18-FDG-PET or A-beta-42 and hippocampal atrophy had the highest positive likelihood ratios (6.45 and 5.56, respectively).

The study was supported by the Swedish Research Council and by a grant from the Italian Ministry of Health. Dr. Frisoni disclosed that he has received personal compensation for activities with Eli Lilly, Bristol-Myers Squibb, Bayer, and several other companies.

dbrunk@frontlinemedcom.com

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Major finding: In predicting short-term incident dementia in mild cognitive impairment, positivity to FDG-PET had the highest positive likelihood ratio (5.82) in the International Working Group diagnostic criteria and the highest positive likelihood ratio in combination with amyloid-beta-42 cerebrospinal level (6.45) in the National Institute on Aging–Alzheimer’s Association diagnostic criteria.

Data source: A study of 73 patients with mild cognitive impairment who were treated at clinics in Brescia, Italy; Amsterdam; and Stockholm.

Disclosures: The study was supported by the Swedish Research Council and by a grant from the Italian Ministry of Health. Dr. Frisoni disclosed that he has received personal compensation for activities with Eli Lilly, Bristol-Myers Squibb, Bayer, and several other companies.