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Florbetapir F 18 amyloid PET and 36-month cognitive decline: a prospective multicenter study.

Doraiswamy PM, Sperling RA, Johnson K, Reiman EM, Wong TZ, Sabbagh MN, Sadowsky CH, Fleisher AS, Carpenter A, Joshi AD, Lu M, Grundman M, Mintun MA, Skovronsky DM, Pontecorvo MJ, AV45-A11 Study GroupAV45-A11 Study Gro - Mol. Psychiatry (2014)

Bottom Line: Aβ+ subjects in all diagnostic groups also showed greater decline on the CDR-SB (P<0.04), a global clinical assessment.Aβ+ subjects did not show significantly greater declines on the ADCS-ADL or Wechsler Memory Scale.Overall, these findings suggest that in CN, MCI and AD subjects, florbetapir PET Aβ+ subjects show greater cognitive and global deterioration over a 3-year follow-up than Aβ- subjects do.

View Article: PubMed Central - PubMed

Affiliation: Duke University Medical Center, Durham, NC, USA.

ABSTRACT
This study was designed to evaluate whether subjects with amyloid beta (Aβ) pathology, detected using florbetapir positron emission tomorgraphy (PET), demonstrated greater cognitive decline than subjects without Aβ pathology. Sixty-nine cognitively normal (CN) controls, 52 with recently diagnosed mild cognitive impairment (MCI) and 31 with probable Alzheimer's disease (AD) dementia were included in the study. PET images obtained in these subjects were visually rated as positive (Aβ+) or negative (Aβ-), blind to diagnosis. Fourteen percent (10/69) of CN, 37% (19/52) of MCI and 68% (21/31) of AD were Aβ+. The primary outcome was change in ADAS-Cog score in MCI subjects after 36 months; however, additional outcomes included change on measures of cognition, function and diagnostic status. Aβ+ MCI subjects demonstrated greater worsening compared with Aβ- subjects on the ADAS-Cog over 36 months (5.66 ± 1.47 vs -0.71 ± 1.09, P = 0.0014) as well as on the mini-mental state exam (MMSE), digit symbol substitution (DSS) test, and a verbal fluency test (P < 0.05). Similar to MCI subjects, Aβ+ CN subjects showed greater decline on the ADAS-Cog, digit-symbol-substitution test and verbal fluency (P<0.05), whereas Aβ+ AD patients showed greater declines in verbal fluency and the MMSE (P < 0.05). Aβ+ subjects in all diagnostic groups also showed greater decline on the CDR-SB (P<0.04), a global clinical assessment. Aβ+ subjects did not show significantly greater declines on the ADCS-ADL or Wechsler Memory Scale. Overall, these findings suggest that in CN, MCI and AD subjects, florbetapir PET Aβ+ subjects show greater cognitive and global deterioration over a 3-year follow-up than Aβ- subjects do.

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(a) Percentage of Aβ+ and Aβ− MCI subjects progressing to dementia or reverting to cognitive normal (CN) status over 36 months. The bars depict the 36-month endpoint diagnostic status of subjects originally classified as MCI at baseline. The red and blue bars titled CN depict the percentage of MCI subjects who reverted to CN by amyloid status. The red and blue bars titled MCI depict the percentage of MCI subjects who continued to be classified as MCI at endpoint (that is, cognitive change was not sufficient to trigger conversion). The red and blue bars titled AD depict the percentage of MCI subjects who progressed to dementia by amyloid status. Conversion to dementia from MCI was almost three times higher in Aβ+ subjects while reversion to CN was almost three times lower than Aβ− subjects. The arrows depict conversion and reversion. Please see text for details. (b) Concomitant and initiation of AD medication use in MCI subjects over 36 months by baseline florbetapir PET status. The proportion of MCI subjects who started the study taking AD medications was greater among Aβ+ vs Aβ− subjects (35.3% vs 3.3% P=0.006). By study end, 70.6% of Aβ+ MCI subjects were taking AD medications vs 23.3% Aβ− MCI (P=0.002) because of the greater percentage who initiated AD medications in Aβ+MCI vs Aβ−MCI (54.5% vs 20.7%). Please see text for details.
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fig3: (a) Percentage of Aβ+ and Aβ− MCI subjects progressing to dementia or reverting to cognitive normal (CN) status over 36 months. The bars depict the 36-month endpoint diagnostic status of subjects originally classified as MCI at baseline. The red and blue bars titled CN depict the percentage of MCI subjects who reverted to CN by amyloid status. The red and blue bars titled MCI depict the percentage of MCI subjects who continued to be classified as MCI at endpoint (that is, cognitive change was not sufficient to trigger conversion). The red and blue bars titled AD depict the percentage of MCI subjects who progressed to dementia by amyloid status. Conversion to dementia from MCI was almost three times higher in Aβ+ subjects while reversion to CN was almost three times lower than Aβ− subjects. The arrows depict conversion and reversion. Please see text for details. (b) Concomitant and initiation of AD medication use in MCI subjects over 36 months by baseline florbetapir PET status. The proportion of MCI subjects who started the study taking AD medications was greater among Aβ+ vs Aβ− subjects (35.3% vs 3.3% P=0.006). By study end, 70.6% of Aβ+ MCI subjects were taking AD medications vs 23.3% Aβ− MCI (P=0.002) because of the greater percentage who initiated AD medications in Aβ+MCI vs Aβ−MCI (54.5% vs 20.7%). Please see text for details.

Mentions: The proportion of MCI subjects progressing to AD dementia or reverting to CN over the 36-month study can be seen in Figure 3a. Overall, more MCI Aβ+ subjects converted to dementia and fewer converted to CN status than Aβ− subjects (P=0.036). MCI subjects rated Aβ+ had an ~3.5-fold higher conversion rate to AD dementia (6/17 Aβ+ MCI subjects (35.3%) vs 3/30 rated Aβ− (10.0%); P=0.054). Fewer Aβ+ (1/17 (5.9%)] vs Aβ− (5/30, (16.7%)) MCI subjects reverted to CN status, although this difference was not statistically significant. Among the 30 MCI Aβ− subjects, 27 failed to progress to dementia and failed to show clinically significant worsening (a 4-point decline on the ADAS-Cog) over 36 months resulting in a negative predictive value of florbetapir PET for both outcomes of 90% (95% CI: 74.4%-96.5%). In MCI subjects, the positive predictive value was 47% with respect to a clinically significant ADAS-Cog decline by 4 points and 35.3% for conversion to AD dementia. The positive and negative predictive values based on SUVR were similar to those for the visual reads.


Florbetapir F 18 amyloid PET and 36-month cognitive decline: a prospective multicenter study.

Doraiswamy PM, Sperling RA, Johnson K, Reiman EM, Wong TZ, Sabbagh MN, Sadowsky CH, Fleisher AS, Carpenter A, Joshi AD, Lu M, Grundman M, Mintun MA, Skovronsky DM, Pontecorvo MJ, AV45-A11 Study GroupAV45-A11 Study Gro - Mol. Psychiatry (2014)

(a) Percentage of Aβ+ and Aβ− MCI subjects progressing to dementia or reverting to cognitive normal (CN) status over 36 months. The bars depict the 36-month endpoint diagnostic status of subjects originally classified as MCI at baseline. The red and blue bars titled CN depict the percentage of MCI subjects who reverted to CN by amyloid status. The red and blue bars titled MCI depict the percentage of MCI subjects who continued to be classified as MCI at endpoint (that is, cognitive change was not sufficient to trigger conversion). The red and blue bars titled AD depict the percentage of MCI subjects who progressed to dementia by amyloid status. Conversion to dementia from MCI was almost three times higher in Aβ+ subjects while reversion to CN was almost three times lower than Aβ− subjects. The arrows depict conversion and reversion. Please see text for details. (b) Concomitant and initiation of AD medication use in MCI subjects over 36 months by baseline florbetapir PET status. The proportion of MCI subjects who started the study taking AD medications was greater among Aβ+ vs Aβ− subjects (35.3% vs 3.3% P=0.006). By study end, 70.6% of Aβ+ MCI subjects were taking AD medications vs 23.3% Aβ− MCI (P=0.002) because of the greater percentage who initiated AD medications in Aβ+MCI vs Aβ−MCI (54.5% vs 20.7%). Please see text for details.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4195975&req=5

fig3: (a) Percentage of Aβ+ and Aβ− MCI subjects progressing to dementia or reverting to cognitive normal (CN) status over 36 months. The bars depict the 36-month endpoint diagnostic status of subjects originally classified as MCI at baseline. The red and blue bars titled CN depict the percentage of MCI subjects who reverted to CN by amyloid status. The red and blue bars titled MCI depict the percentage of MCI subjects who continued to be classified as MCI at endpoint (that is, cognitive change was not sufficient to trigger conversion). The red and blue bars titled AD depict the percentage of MCI subjects who progressed to dementia by amyloid status. Conversion to dementia from MCI was almost three times higher in Aβ+ subjects while reversion to CN was almost three times lower than Aβ− subjects. The arrows depict conversion and reversion. Please see text for details. (b) Concomitant and initiation of AD medication use in MCI subjects over 36 months by baseline florbetapir PET status. The proportion of MCI subjects who started the study taking AD medications was greater among Aβ+ vs Aβ− subjects (35.3% vs 3.3% P=0.006). By study end, 70.6% of Aβ+ MCI subjects were taking AD medications vs 23.3% Aβ− MCI (P=0.002) because of the greater percentage who initiated AD medications in Aβ+MCI vs Aβ−MCI (54.5% vs 20.7%). Please see text for details.
Mentions: The proportion of MCI subjects progressing to AD dementia or reverting to CN over the 36-month study can be seen in Figure 3a. Overall, more MCI Aβ+ subjects converted to dementia and fewer converted to CN status than Aβ− subjects (P=0.036). MCI subjects rated Aβ+ had an ~3.5-fold higher conversion rate to AD dementia (6/17 Aβ+ MCI subjects (35.3%) vs 3/30 rated Aβ− (10.0%); P=0.054). Fewer Aβ+ (1/17 (5.9%)] vs Aβ− (5/30, (16.7%)) MCI subjects reverted to CN status, although this difference was not statistically significant. Among the 30 MCI Aβ− subjects, 27 failed to progress to dementia and failed to show clinically significant worsening (a 4-point decline on the ADAS-Cog) over 36 months resulting in a negative predictive value of florbetapir PET for both outcomes of 90% (95% CI: 74.4%-96.5%). In MCI subjects, the positive predictive value was 47% with respect to a clinically significant ADAS-Cog decline by 4 points and 35.3% for conversion to AD dementia. The positive and negative predictive values based on SUVR were similar to those for the visual reads.

Bottom Line: Aβ+ subjects in all diagnostic groups also showed greater decline on the CDR-SB (P<0.04), a global clinical assessment.Aβ+ subjects did not show significantly greater declines on the ADCS-ADL or Wechsler Memory Scale.Overall, these findings suggest that in CN, MCI and AD subjects, florbetapir PET Aβ+ subjects show greater cognitive and global deterioration over a 3-year follow-up than Aβ- subjects do.

View Article: PubMed Central - PubMed

Affiliation: Duke University Medical Center, Durham, NC, USA.

ABSTRACT
This study was designed to evaluate whether subjects with amyloid beta (Aβ) pathology, detected using florbetapir positron emission tomorgraphy (PET), demonstrated greater cognitive decline than subjects without Aβ pathology. Sixty-nine cognitively normal (CN) controls, 52 with recently diagnosed mild cognitive impairment (MCI) and 31 with probable Alzheimer's disease (AD) dementia were included in the study. PET images obtained in these subjects were visually rated as positive (Aβ+) or negative (Aβ-), blind to diagnosis. Fourteen percent (10/69) of CN, 37% (19/52) of MCI and 68% (21/31) of AD were Aβ+. The primary outcome was change in ADAS-Cog score in MCI subjects after 36 months; however, additional outcomes included change on measures of cognition, function and diagnostic status. Aβ+ MCI subjects demonstrated greater worsening compared with Aβ- subjects on the ADAS-Cog over 36 months (5.66 ± 1.47 vs -0.71 ± 1.09, P = 0.0014) as well as on the mini-mental state exam (MMSE), digit symbol substitution (DSS) test, and a verbal fluency test (P < 0.05). Similar to MCI subjects, Aβ+ CN subjects showed greater decline on the ADAS-Cog, digit-symbol-substitution test and verbal fluency (P<0.05), whereas Aβ+ AD patients showed greater declines in verbal fluency and the MMSE (P < 0.05). Aβ+ subjects in all diagnostic groups also showed greater decline on the CDR-SB (P<0.04), a global clinical assessment. Aβ+ subjects did not show significantly greater declines on the ADCS-ADL or Wechsler Memory Scale. Overall, these findings suggest that in CN, MCI and AD subjects, florbetapir PET Aβ+ subjects show greater cognitive and global deterioration over a 3-year follow-up than Aβ- subjects do.

Show MeSH
Related in: MedlinePlus