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Neurology. 2016 Apr 12;86(15):1377-1385. doi: 10.1212/WNL.0000000000002576. Epub 2016 Mar 11.

Amyloid negativity in patients with clinically diagnosed Alzheimer disease and MCI.

Collaborators (224)

Weiner M, Aisen P, Weiner M, Aisen P, Petersen R, Jack CR Jr, Jagust W, Trojanowki JQ, Toga AW, Beckett L, Green RC, Gamst A, Saykin AJ, Morris J, Potter WZ, Green RC, Montine T, Petersen R, Aisen P, Gamst A, Thomas RG, Donohue M, Walter S, Jack CR Jr, Dale A, Bernstein M, Felmlee J, Fox N, Thompson P, Schuff N, Alexander G, DeCarli C, Jagust W, Bandy D, Koeppe RA, Foster N, Reiman EM, Chen K, Mathis C, Morris J, Cairns NJ, Taylor-Reinwald L, Trojanowki JQ, Shaw L, Lee VM, Korecka M, Toga AW, Crawford K, Neu S, Beckett L, Harvey D, Gamst A, Kornak J, Saykin AJ, Foroud TM, Potkin S, Shen L, Kachaturian Z, Frank R, Snyder PJ, Molchan S, Kaye J, Dolen S, Quinn J, Schneider L, Pawluczyk S, Spann BM, Brewer J, Vanderswag H, Heidebrink JL, Lord JL, Petersen R, Johnson K, Doody RS, Villanueva-Meyer J, Chowdhury M, Stern Y, Honig LS, Bell KL, Morris JC, Mintun MA, Schneider S, Marson D, Griffith R, Clark D, Grossman H, Tang C, Marzloff G, deToledo-Morrell L, Shah RC, Duara R, Varon D, Roberts P, Albert MS, Kozauer N, Zerrate M, Rusinek H, de Leon MJ, De Santi SM, Doraiswamy PM, Petrella JR, Aiello M, Arnold S, Karlawish JH, Wolk D, Smith CD, Given CA 2nd, Hardy P, Lopez OL, Oakley M, Simpson DM, Ismail MS, Brand C, Richard J, Mulnard RA, Thai G, Mc-Adams-Ortiz C, Diaz-Arrastia R, Martin-Cook K, DeVous M, Levey AI, Lah JJ, Cellar JS, Burns JM, Anderson HS, Laubinger MM, Apostolova L, Silverman DHS, Lu PH, Graff-Radford NR, Parfitt F, Johnson H, Farlow M, Herring S, Hake AM, van Dyck CH, MacAvoy MG, Benincasa AL, Chertkow H, Bergman H, Hosein C, Black S, Stefanovic B, Caldwell C, Robin Hsiung GY, Feldman H, Assaly M, Kertesz A, Rogers J, Trost D, Bernick C, Munic D, Wu CK, Johnson N, Mesulam M, Sadowsky C, Martinez W, Villena T, Turner RS, Johnson K, Reynolds B, Sperling RA, Rentz DM, Johnson KA, Rosen A, Tinklenberg J, Ashford W, Sabbagh M, Connor D, Jacobson S, Killiany R, Norbash A, Nair A, Obisesan TO, Jayam-Trouth A, Wang P, Lerner A, Hudson L, Ogrocki P, DeCarli C, Fletcher E, Carmichael O, Kittur S, Borrie M, Lee TY, Bartha DR, Johnson S, Asthana S, Carlsson CM, Potkin SG, Preda A, Nguyen D, Tariot P, Fleisher A, Reeder S, Bates V, Capote H, Rainka M, Hendin BA, Scharre DW, Kataki M, Zimmerman EA, Celmins D, Brown AD, Pearlson G, Blank K, Anderson K, Saykin AJ, Santulli RB, Englert J, Williamson JD, Sink KM, Watkins F, Ott BR, Stopa E, Tremont G, Salloway S, Malloy P, Correia S, Rosen HJ, Miller BL, Mintzer J, Longmire CF, Spicer K.

Author information

1
From Helen Wills Neuroscience Institute (S.M.L., A.H., W.J.J.), University of California, Berkeley; and Life Sciences Division (S.M.L., A.F., W.J.J.), Lawrence Berkeley National Laboratory, CA. slandau@berkeley.edu.
2
From Helen Wills Neuroscience Institute (S.M.L., A.H., W.J.J.), University of California, Berkeley; and Life Sciences Division (S.M.L., A.F., W.J.J.), Lawrence Berkeley National Laboratory, CA.

Abstract

OBJECTIVE:

To examine the clinical and biomarker characteristics of patients with amyloid-negative Alzheimer disease (AD) and mild cognitive impairment (MCI) from the Alzheimer's Disease Neuroimaging Initiative (ADNI), a prospective cohort study.

METHODS:

We first investigated the reliability of florbetapir- PET in patients with AD and patients with MCI using CSF-Aβ1-42 as a comparison amyloid measurement. We then compared florbetapir- vs florbetapir+ patients with respect to several AD-specific biomarkers, baseline and longitudinal cognitive measurements, and demographic and clinician report data.

RESULTS:

Florbetapir and CSF-Aβ1-42 +/- status agreed for 98% of ADs (89% of MCIs), indicating that most florbetapir- scans were a reliable representation of amyloid status. Florbetapir- AD (n = 27/177; 15%) and MCI (n = 74/217, 34%) were more likely to be APOE4-negative (MCI 83%, AD 96%) than their florbetapir+ counterparts (MCI 30%, AD 24%). Florbetapir- patients also had less AD-specific hypometabolism, lower CSF p-tau and t-tau, and better longitudinal cognitive performance, and were more likely to be taking medication for depression. In MCI only, florbetapir- participants had less hippocampal atrophy and hypometabolism and lower functional activity questionnaire scores compared to florbetapir+ participants.

CONCLUSIONS:

Overall, image analysis problems do not appear to be a primary explanation of amyloid negativity. Florbetapir- ADNI patients have a variety of clinical and biomarker features that differ from their florbetapir+ counterparts, suggesting that one or more non-AD etiologies (which may include vascular disease and depression) account for their AD-like phenotype.

PMID:
26968515
PMCID:
PMC4831042
DOI:
10.1212/WNL.0000000000002576
[Indexed for MEDLINE]
Free PMC Article

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