Skip to main content
×
Home
    • Aa
    • Aa
  • Get access
    Check if you have access via personal or institutional login
  • Cited by 6
  • Cited by
    This article has been cited by the following publications. This list is generated based on data provided by CrossRef.

    Clark, Lindsay R. Racine, Annie M. Koscik, Rebecca L. Okonkwo, Ozioma C. Engelman, Corinne D. Carlsson, Cynthia M. Asthana, Sanjay Bendlin, Barbara B. Chappell, Rick Nicholas, Christopher R. Rowley, Howard A. Oh, Jennifer M. Hermann, Bruce P. Sager, Mark A. Christian, Bradley T. and Johnson, Sterling C. 2016. Beta-amyloid and cognitive decline in late middle age: Findings from the Wisconsin Registry for Alzheimer's Prevention study. Alzheimer's & Dementia, Vol. 12, Issue. 7, p. 805.


    Bonner-Jackson, Aaron Mahmoud, Shamseldeen Miller, Justin and Banks, Sarah J 2015. Verbal and non-verbal memory and hippocampal volumes in a memory clinic population. Alzheimer's Research & Therapy, Vol. 7, Issue. 1,


    Lim, Yen Ying Villemagne, Victor L. Pietrzak, Robert H. Ames, David Ellis, Kathryn A. Harrington, Karra Snyder, Peter J. Martins, Ralph N. Masters, Colin L. Rowe, Christopher C. and Maruff, Paul 2015. APOE ε4 moderates amyloid-related memory decline in preclinical Alzheimer's disease. Neurobiology of Aging, Vol. 36, Issue. 3, p. 1239.


    Nicholas, Christopher R. Okonkwo, Ozioma C. Bendlin, Barbara B. Oh, Jennifer M. Asthana, Sanjay Rowley, Howard A. Hermann, Bruce Sager, Mark A. and Johnson, Sterling C. 2015. Posteromedial hyperactivation during episodic recognition among people with memory decline: findings from the WRAP study. Brain Imaging and Behavior, Vol. 9, Issue. 4, p. 690.


    Racine, Annie M. Koscik, Rebecca L. Nicholas, Christopher R. Clark, Lindsay R. Okonkwo, Ozioma C. Oh, Jennifer M. Hillmer, Ansel T. Murali, Dhanabalan Barnhart, Todd E. Betthauser, Tobey J. Gallagher, Catherine L. Rowley, Howard A. Dowling, N. Maritza Asthana, Sanjay Bendlin, Barbara B. Blennow, Kaj Zetterberg, Henrik Carlsson, Cynthia M. Christian, Bradley T. and Johnson, Sterling C. 2016. Cerebrospinal fluid ratios with Aβ42 predict preclinical brain β-amyloid accumulation. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring, Vol. 2, p. 27.


    Racine, Annie M. Adluru, Nagesh Alexander, Andrew L. Christian, Bradley T. Okonkwo, Ozioma C. Oh, Jennifer Cleary, Caitlin A. Birdsill, Alex Hillmer, Ansel T. Murali, Dhanabalan Barnhart, Todd E. Gallagher, Catherine L. Carlsson, Cynthia M. Rowley, Howard A. Dowling, N. Maritza Asthana, Sanjay Sager, Mark A. Bendlin, Barbara B. and Johnson, Sterling C. 2014. Associations between white matter microstructure and amyloid burden in preclinical Alzheimer's disease: A multimodal imaging investigation. NeuroImage: Clinical, Vol. 4, p. 604.


    ×
  • Journal of the International Neuropsychological Society, Volume 20, Issue 4
  • April 2014, pp. 422-433

Amyloid Burden, Neuronal Function, and Cognitive Decline in Middle-Aged Adults at Risk for Alzheimer's Disease

  • Ozioma C. Okonkwo (a1) (a2) (a3), Jennifer M. Oh (a1) (a2), Rebecca Koscik (a3), Erin Jonaitis (a3), Caitlin A. Cleary (a1) (a2), N. Maritza Dowling (a2) (a4), Barbara B. Bendlin (a1) (a2) (a3), Asenath LaRue (a3), Bruce P. Hermann (a2) (a3) (a5), Todd E. Barnhart (a6), Dhanabalan Murali (a6), Howard A. Rowley (a2) (a7), Cynthia M. Carlsson (a1) (a2) (a3), Catherine L. Gallagher (a1) (a2) (a5), Sanjay Asthana (a1) (a2) (a3), Mark A. Sager (a2) (a3), Brad T. Christian (a2) (a6) and Sterling C. Johnson (a1) (a2) (a3)
  • DOI: http://dx.doi.org/10.1017/S1355617714000113
  • Published online: 11 March 2014
Abstract
Abstract

The relative influence of amyloid burden, neuronal structure and function, and prior cognitive performance on prospective memory decline among asymptomatic late middle-aged individuals at risk for Alzheimer's disease (AD) is currently unknown. We investigated this using longitudinal cognitive data from 122 middle-aged adults (21 “Decliners” and 101 “Stables”) enrolled in the Wisconsin Registry for Alzheimer's Prevention who underwent multimodality neuroimaging [11C-Pittsburgh Compound B (PiB), 18F-fluorodeoxyglucose (FDG), and structural/functional magnetic resonance imaging (fMRI)] 5.7 ± 1.4 years (range = 2.9–8.9) after their baseline cognitive assessment. Covariate-adjusted regression analyses revealed that the only imaging measure that significantly distinguished Decliners from Stables (p = .027) was a Neuronal Function composite derived from FDG and fMRI. In contrast, several cognitive measures, especially those that tap episodic memory, significantly distinguished the groups (p's<.05). Complementary receiver operating characteristic curve analyses identified the Brief Visuospatial Memory Test-Revised (BVMT-R) Total (.82 ± .05, p < .001), the BVMT-R Delayed Recall (.73 ± .06, p = .001), and the Reading subtest from the Wide-Range Achievement Test-III (.72 ± .06, p = .002) as the top three measures that best discriminated the groups. These findings suggest that early memory test performance might serve a more clinically pivotal role in forecasting future cognitive course than is currently presumed. (JINS, 2014, 20, 1–12)

Copyright
Corresponding author
Correspondence and reprint requests to: Ozioma C. Okonkwo, Department of Medicine and Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792. E-mail: ozioma@medicine.wisc.edu.
Linked references
Hide All

This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

Alzheimer's Association. (2012). 2012 Alzheimer's disease facts and figures. Alzheimer's & Dementia, 8(2), 131168. doi:10.1016/j.jalz.2012.02.001

A.L. Benton (1994). Neuropsychological assessment. Annual Review of Psychology, 45, 123. doi:10.1146/annurev.ps.45.020194.000245

D. Blacker , H. Lee , A. Muzikansky , E.C. Martin , R. Tanzi , J.J. McArdle , M. Albert (2007). Neuropsychological measures in normal individuals that predict subsequent cognitive decline. Archives of Neurology, 64(6), 862871. doi:10.1001/archneur.64.6.862

R.L. Buckner , A.Z. Snyder , B.J. Shannon , G. LaRossa , R. Sachs , A.F. Fotenos , M.A. Mintun (2005). Molecular, structural, and functional characterization of Alzheimer's disease: Evidence for a relationship between default activity, amyloid, and memory. Journal of Neuroscience, 25(34), 77097717. doi:10.1523/JNEUROSCI.2177-05.2005

N.J. Cairns , M.D. Ikonomovic , T. Benzinger , M. Storandt , A.M. Fagan , A.R. Shah , J.C. Morris (2009). Absence of Pittsburgh compound B detection of cerebral amyloid beta in a patient with clinical, cognitive, and cerebrospinal fluid markers of Alzheimer disease: A case report. Archives of Neurology, 66(12), 15571562. doi:10.1001/archneurol.2009.279

G. Chetelat (2013). Alzheimer disease: Abeta-independent processes-rethinking preclinical AD. Nature Reviews Neurology, 9(3), 123124. doi:10.1038/nrneurol.2013.21

G. Chételat , R. La Joie , N. Villain , A. Perrotin , V. de La Sayette , F. Eustache , R. Vandenberghe (2013). Amyloid imaging in cognitively normal individuals, at-risk populations and preclinical Alzheimer's disease. Neuroimage: Clinical, 2, 356365. doi:http://dx.doi.org/10.1016/j.nicl.2013.02.006

B.T. Christian , N.T. Vandehey , J.M. Floberg , C.A. Mistretta (2010). Dynamic PET denoising with HYPR processing. Journal of Nuclear Medicine, 51(7), 11471154. doi:10.2967/jnumed.109.073999

E.H. Corder , E. Ghebremedhin , M.G. Taylor , D.R. Thal , T.G. Ohm , H. Braak (2004). The biphasic relationship between regional brain senile plaque and neurofibrillary tangle distributions: Modification by age, sex, and APOE polymorphism. Annals of the New York Academy of Sciences, 1019, 2428. doi:10.1196/annals.1297.005

R.S. Desikan , L.K. McEvoy , W.K. Thompson , D. Holland , J.B. Brewer , P.S. Aisen , A.M. Dale (2012). Amyloid-beta—associated clinical decline occurs only in the presence of elevated P-tau. Archives of Neurology, 69(6), 709713. doi:10.1001/archneurol.2011.3354

D.A. Drachman (2006). Aging of the brain, entropy, and Alzheimer disease. Neurology, 67(8), 13401352. doi:10.1212/01.wnl.0000240127.89601.83

M.F. Elias , A. Beiser , P.A. Wolf , R. Au , R.F. White , R.B. D'Agostino (2000). The preclinical phase of alzheimer disease: A 22-year prospective study of the Framingham Cohort. Archives of Neurology, 57(6), 808813.

M. Ewers , P. Insel , W.J. Jagust , L. Shaw , J.Q. Trojanowski , P. Aisen , M.W. Weiner (2012). CSF biomarker and PIB-PET-derived beta-amyloid signature predicts metabolic, gray matter, and cognitive changes in nondemented subjects. Cerebral Cortex, 22(9), 19932004. doi:10.1093/cercor/bhr271

J.M. Floberg , C.A. Mistretta , J.P. Weichert , L.T. Hall , J.E. Holden , B.T. Christian (2012). Improved kinetic analysis of dynamic PET data with optimized HYPR-LR. Medical Physics, 39(6), 33193331. doi:10.1118/1.4718669

M.F. Folstein , S.E. Folstein , P.R. McHugh (1975). Mini-mental state: A practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research, 12, 189198.

T. Hedden , H. Oh , A.P. Younger , T.A. Patel (2013). Meta-analysis of amyloid-cognition relations in cognitively normal older adults. Neurology, 80(14), 13411348. doi:10.1212/WNL.0b013e31828ab35d

W. Huijbers , P. Vannini , R.A. Sperling , C.M.P., R. Cabeza , S.M. Daselaar (2012). Explaining the encoding/retrieval flip: Memory-related deactivations and activations in the posteromedial cortex. Neuropsychologia, 50(14), 37643774. doi:10.1016/j.neuropsychologia.2012.08.021

C.R. Jack Jr., D.S. Knopman , W.J. Jagust , R.C. Petersen , M.W. Weiner , P.S. Aisen , J.Q. Trojanowski (2013). Tracking pathophysiological processes in Alzheimer's disease: An updated hypothetical model of dynamic biomarkers. Lancet Neurology, 12(2), 207216. doi:10.1016/S1474-4422(12)70291-0

C.R. Jack Jr., D.S. Knopman , W.J. Jagust , L.M. Shaw , P.S. Aisen , M.W. Weiner , J.Q. Trojanowski (2010). Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade. Lancet Neurology, 9(1), 119128. doi:10.1016/S1474-4422(09)70299-6

C.R. Jack Jr., V.J. Lowe , S.D. Weigand , H.J. Wiste , M.L. Senjem , D.S. Knopman , R.C. Petersen (2009). Serial PIB and MRI in normal, mild cognitive impairment and Alzheimer's disease: Implications for sequence of pathological events in Alzheimer's disease. Brain, 132(Pt 5), 13551365. doi:10.1093/brain/awp062

W.J. Jagust , D. Bandy , K. Chen , N.L. Foster , S.M. Landau , C.A. Mathis , R.A. Koeppe (2010). The Alzheimer's Disease Neuroimaging Initiative positron emission tomography core. Alzheimer's & Dementia, 6(3), 221229. doi:10.1016/j.jalz.2010.03.003

S.C. Johnson , T.W. Schmitz , C.H. Moritz , M.E. Meyerand , H.A. Rowley , A.L. Alexander , G.E. Alexander (2006). Activation of brain regions vulnerable to Alzheimer's disease: The effect of mild cognitive impairment. Neurobiology of Aging, 27(11), 16041612. doi:10.1016/j.neurobiolaging.2005.09.017

C.H. Kawas , M.M. Corrada , R. Brookmeyer , A. Morrison , S.M. Resnick , A.B. Zonderman , D. Arenberg (2003). Visual memory predicts Alzheimer's disease more than a decade before diagnosis. Neurology, 60(7), 10891093.

S.M. Landau , D. Harvey , C.M. Madison , R.A. Koeppe , E.M. Reiman , N.L. Foster , W.J. Jagust (2011). Associations between cognitive, functional, and FDG-PET measures of decline in AD and MCI. Neurobiology of Aging, 32(7), 12071218. doi:10.1016/j.neurobiolaging.2009.07.002

S.M. Landau , D. Harvey , C.M. Madison , E.M. Reiman , N.L. Foster , P.S. Aisen , W.J. Jagust (2010). Comparing predictors of conversion and decline in mild cognitive impairment. Neurology, 75(3), 230238. doi:10.1212/WNL.0b013e3181e8e8b8

S.M. Landau , M.A. Mintun , A.D. Joshi , R.A. Koeppe , R.C. Petersen , P.S. Aisen , W.J. Jagust (2012). Amyloid deposition, hypometabolism, and longitudinal cognitive decline. Annals of Neurology, 72(4), 578586. doi:10.1002/ana.23650

Y.Y. Lim , K.A. Ellis , R.H. Pietrzak , D. Ames , D. Darby , K. Harrington , P. Maruff (2012). Stronger effect of amyloid load than APOE genotype on cognitive decline in healthy older adults. Neurology, 79(16), 16451652. doi:10.1212/WNL.0b013e31826e9ae6

R.Y. Lo , A.E. Hubbard , L.M. Shaw , J.Q. Trojanowski , R.C. Petersen , P.S. Aisen , W.J. Jagust (2011). Longitudinal change of biomarkers in cognitive decline. Archives of Neurology, 68(10), 12571266. doi:10.1001/archneurol.2011.123

J.A. Maldjian , P.J. Laurienti , R.A. Kraft , J.H. Burdette (2003). An automated method for neuroanatomic and cytoarchitectonic atlas-based interrogation of fMRI data sets. Neuroimage, 19, 12331239. doi:S1053811903001691 [pii]

J.J. Manly , N. Schupf , M.X. Tang , Y. Stern (2005). Cognitive decline and literacy among ethnically diverse elders. Journal of Geriatric Psychiatry and Neurology, 18(4), 213217. doi:10.1177/0891988705281868

J.C. Morris (1993). The Clinical Dementia Rating (CDR): Current version and scoring rules. Neurology, 43, 24122414.

J.C. Morris , C.M. Roe , E.A. Grant , D. Head , M. Storandt , A.M. Goate , M.A. Mintun (2009). Pittsburgh compound B imaging and prediction of progression from cognitive normality to symptomatic Alzheimer disease. Archives of Neurology, 66(12), 14691475. doi:10.1001/archneurol.2009.269

L. Mosconi , R. Mistur , R. Switalski , M. Brys , L. Glodzik , K. Rich , M.J. de Leon (2009). Declining brain glucose metabolism in normal individuals with a maternal history of Alzheimer disease. Neurology, 72(6), 513520. doi:10.1212/01.wnl.0000333247.51383.43

J.L. O'Brien , K.M. O'Keefe , P.S. LaViolette , A.N. DeLuca , D. Blacker , B.C. Dickerson , R.A. Sperling (2010). Longitudinal fMRI in elderly reveals loss of hippocampal activation with clinical decline. Neurology, 74(24), 19691976. doi:10.1212/WNL.0b013e3181e3966e

O.C. Okonkwo , G. Xu , N.M. Dowling , B.B. Bendlin , A. Larue , B.P. Hermann , S.C. Johnson (2012). Family history of Alzheimer disease predicts hippocampal atrophy in healthy middle-aged adults. Neurology, 78(22), 17691776. doi:10.1212/WNL.0b013e3182583047

J.C. Price , W.E. Klunk , B.J. Lopresti , X. Lu , J.A. Hoge , S.K. Ziolko , C.A. Mathis (2005). Kinetic modeling of amyloid binding in humans using PET imaging and Pittsburgh Compound-B. Journal of Cerebral Blood Flow and Metabolism, 25(11), 15281547. doi:10.1038/sj.jcbfm.9600146

S.M. Resnick , J. Sojkova , Y. Zhou , Y. An , W. Ye , D.P. Holt , D.F. Wong (2010). Longitudinal cognitive decline is associated with fibrillar amyloid-beta measured by [11C]PiB. Neurology, 74(10), 807815. doi:10.1212/WNL.0b013e3181d3e3e9

M.A. Sager , B. Hermann , A. La Rue (2005). Middle-aged children of persons with Alzheimer's disease: APOE genotypes and cognitive function in the Wisconsin Registry for Alzheimer's Prevention. Journal of Geriatric Psychiatry and Neurology, 18(4), 245249. doi:10.1177/0891988705281882

Y.I. Sheline , J.C. Morris , A.Z. Snyder , J.L. Price , Z. Yan , G. D'Angelo , M.A. Mintun (2010). APOE4 allele disrupts resting state fMRI connectivity in the absence of amyloid plaques or decreased CSF Abeta42. Journal of Neuroscience, 30(50), 1703517040. doi:10.1523/JNEUROSCI.3987-10.2010

B.E. Snitz , L.A. Weissfeld , O.L. Lopez , L.H. Kuller , J. Saxton , D.M. Singhabahu , S.T. Dekosky (2013). Cognitive trajectories associated with beta-amyloid deposition in the oldest-old without dementia. Neurology, 80, 13781384. doi:10.1212/WNL.0b013e31828c2fc8

R.A. Sperling , P.S. Aisen , L.A. Beckett , D.A. Bennett , S. Craft , A.M. Fagan , C.H. Phelps (2011). Toward defining the preclinical stages of Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimer's & Dementia, 7(3), 280292. doi:10.1016/j.jalz.2011.03.003

Y. Stern (2012). Cognitive reserve in ageing and Alzheimer's disease. Lancet Neurology, 11(11), 10061012. doi:10.1016/S1474-4422(12)70191-6

P. Vannini , J. O'Brien , K. O'Keefe , M. Pihlajamaki , P. Laviolette , R.A. Sperling (2011). What goes down must come up: Role of the posteromedial cortices in encoding and retrieval. Cerebral Cortex, 21(1), 2234. doi:10.1093/cercor/bhq051

V.L. Villemagne , S. Burnham , P. Bourgeat , B. Brown , K.A. Ellis , O. Salvado , C.L. Masters (2013). Amyloid beta deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer's disease: A prospective cohort study. Lancet Neurology, 12(4), 357367. doi:10.1016/S1474-4422(13)70044-9

M. Wirth , C.M. Madison , G.D. Rabinovici , H. Oh , S.M. Landau , W.J. Jagust (2013). Alzheimer's disease neurodegenerative biomarkers are associated with decreased cognitive function but not beta-amyloid in cognitively normal older individuals. Journal of Neuroscience, 33(13), 55535563. doi:10.1523/JNEUROSCI.4409-12.2013

M. Wirth , H. Oh , E.C. Mormino , C. Markley , S.M. Landau , W.J. Jagust (2013). The effect of amyloid beta on cognitive decline is modulated by neural integrity in cognitively normal elderly. Alzheimer's & Dementia. doi:10.1016/j.jalz.2012.10.012

G. Xu , D.G. McLaren , M.L. Ries , M.E. Fitzgerald , B.B. Bendlin , H.A. Rowley , S.C. Johnson (2009). The influence of parental history of Alzheimer's disease and apolipoprotein E epsilon4 on the BOLD signal during recognition memory. Brain, 132(Pt 2), 383391. doi:10.1093/brain/awn254

X. Zhou , N. Obuchowski , D. McClish (2011). Statistical methods in diagnostic medicine (2nd ed). Hoboken, NJ: John Wiley & Sons, Inc.

Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Journal of the International Neuropsychological Society
  • ISSN: 1355-6177
  • EISSN: 1469-7661
  • URL: /core/journals/journal-of-the-international-neuropsychological-society
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Keywords:

Type Description Title
UNKNOWN
Supplementary Materials

Okonkwo Supplementary Material
Text

 Unknown (152 KB)
152 KB