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Detectable Neuropsychological Differences in Early Preclinical Alzheimer’s Disease: A Meta-Analysis

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A Correction to this article was published on 23 December 2017

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Abstract

The development of methods for in vivo detection of cerebral beta amyloid retention and tau accumulation have been increasingly useful in characterizing preclinical Alzheimer’s disease (AD). While the association between these biomarkers and eventual AD has been demonstrated among cognitively intact older adults, the link between biomarkers and neurocognitive ability remains unclear. We conducted a meta-analysis to test the hypothesis that cognitively intact older adults would show statistically discernable differences in neuropsychological performance by amyloid status (amyloid negative = A-, amyloid positive = A+). We secondarily hypothesized a third group characterized by either CSF tau pathology or neurodegeneration, in addition to amyloidosis (A+/N+ or Stage 2), would show lower neuropsychology scores than the amyloid positive group (A+/N- or Stage 1) when compared to the amyloid negative group. Pubmed, PsychINFO, and other sources were searched for relevant articles, yielding 775 total sources. After review for inclusion/exclusion criteria, duplicates, and risk of bias, 61 studies were utilized in the final meta-analysis. Results showed A+ was associated with poorer performance in the domains of global cognitive function, memory, language, visuospatial ability, processing speed, and attention/working memory/executive functions when compared to A-. A+/N+ showed lower performances on memory measures when compared to A+/N- in secondary analyses based on a smaller subset of studies. Results support the notion that neuropsychological measures are sensitive to different stages of preclinical AD among cognitively intact older adults. Further research is needed to determine what constitutes meaningful differences in neuropsychological performance among cognitively intact older adults.

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  • 23 December 2017

    Errors were discovered in the reporting of processing speed data that do not impact the interpretation of findings.

References

  • Aizenstein, H. J., Nebes, R. D., Saxton, J. A., et al. (2008). Frequent amyloid deposition without significant cognitive impairment among the elderly. Archives of Neurology, 65(11), 1509–1517.

    Article  PubMed  PubMed Central  Google Scholar 

  • Alcolea, D., Martínez-Lage, P., Sánchez-Juan, P., et al. (2015). Amyloid precursor protein metabolism and inflammation markers in preclinical Alzheimer disease. Neurology, 85(7), 626–633.

    Article  CAS  PubMed  Google Scholar 

  • Amariglio, R. E., Becker, J. A., Carmasin, J., et al. (2012). Subjective cognitive complaints and amyloid burden in cognitively normal older individuals. Neuropsychologia, 50, 2880–2886.

    Article  PubMed  PubMed Central  Google Scholar 

  • Amariglio, R. E., Mormino, E. C., Pietras, A. C., et al. (2015). Subjective cognitive concerns, amyloid-β, and neurodegeneration in clinically normal elderly. Neurology, 85(1), 56–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Andreasen, N., Minthon, L., Davidsson, P., et al. (2001). Evaluation of CSF-tau and CSF-Aβ42 as diagnostic markers for Alzheimer disease in clinical practice. Archives of Neurology, 58, 373–379.

    Article  CAS  PubMed  Google Scholar 

  • Ayutyanont, N., Langbaum, J. B., Hendrix, S. B., et al. (2014). The Alzheimer’s Precention initiative composite cognitive test score: Sample size estimates for the evaluation of preclinical Alzheimer’s disease treatments in presenilin 1 E280A mutation carriers. The Journal of Clinical Psychiatry, 75, 652–660.

    Article  PubMed  PubMed Central  Google Scholar 

  • Besson, F. L., La Joie, R., Doeuvre, L., et al. (2015). Cognitive and brain profiles associated with current neuroimaging biomarkers of preclinical Alzheimer's disease. The Journal of Neuroscience, 35(29), 10402–10411.

    Article  CAS  PubMed  Google Scholar 

  • Borenstein, M., Hedges, L. V., Higgins, J. P. T., & Rothstein, H. R. (2009). Introduction to meta-analysis. West Sussex: Wiley.

    Book  Google Scholar 

  • Braak, H., & Del Tredici, K. (2015). The preclinical phase of the pathological process underlying sporadic Alzheimer’s disease. Brain, 138, 2814–2833.

    Article  PubMed  Google Scholar 

  • Buckley, R. F., Maruff, P., Ames, D., et al. (2016). Subjective memory decline predicts greater rates of clinical progression in preclinical Alzheimer's disease. Alzheimer’s & Dementia, 12(7), 796–804.

    Article  Google Scholar 

  • Chen, K., Roontiva, A., Thiyyagura, P., et al. (2015). Improved power for characterizing longitudinal amyloid-β PET changes and evaluating amyloid-modifying treatments with a cerebral white matter reference region. The Journal of Nuclear Medicine, 56(4), 560–566.

    Article  CAS  PubMed  Google Scholar 

  • Chételat, G., Villemagne, V. L., Pike, K. E., et al. (2010). Larger temporal volume in elderly with high versus low beta-amyloid deposition. Brain, 133(11), 3349–3358.

    Article  PubMed  Google Scholar 

  • Chételat, G., Villemagne, V. L., Villain, N., et al. (2012). Accelerated cortical atrophy in cognitively normal elderly with high β-amyloid deposition. Neurology, 78(7), 477–484.

    Article  PubMed  Google Scholar 

  • Cochran, W. G. (1954). The combination of estimates from different experiments. Biometrics, 1, 101–129.

    Article  Google Scholar 

  • Donohue, M. C., Sperling, R. A., Salmon, D. P., et al. (2014). The preclinical Alzheimer cognitive composite: Measuring amyloid-related decline. JAMA Neurology, 71(8), 961–970.

    Article  PubMed  PubMed Central  Google Scholar 

  • Doraiswamy, P. M., Sperling, R. A., Coleman, R. E., et al. (2012). Amyloid-β assessed by florbetapir F 18 PET and 18-month cognitive decline: A multicenter study. Neurology, 79(16), 1636–1644.

    Article  CAS  PubMed  Google Scholar 

  • Doraiswamy, P. M., Sperling, R. A., Johnson, K., et al. (2014). Florbetapir F 18 amyloid PET and 36-month cognitive decline: A prospective multicenter study. Molecular Psychiatry, 19(9), 1044–1051.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dubois, B., Hampel, H., Feldman, H. H., Scheltens, P., Aisen, P., Andrieu, S., Jack, C. R. (2016). Preclinical Alzheimer’s disease: Definition, natural history, and diagnostic criteria. Alzheimer’s and Dementia, 12, 292–323.

  • Duff, K., Norman, N. L., & Hoffman, J. M. (2014). Practice effects and amyloid deposition: Preliminary data on a method for enriching samples in clinical trials. Alzheimer’s Dis Assoc Disord, 28, 247–252.

    Article  CAS  Google Scholar 

  • Edmonds, E. C., Delano-Wood, L., Galasko, D. R., et al. (2015). Subtle cognitive decline and biomarker staging in preclinical Alzheimer’s disease. Journal of Alzheimer’s Disease, 47, 231–242.

    Article  PubMed  PubMed Central  Google Scholar 

  • Elman, J. A., Oh, H., Madison, C. M., et al. (2014). Neural compensation in older people with brain amyloid-β deposition. Nature Neuroscience, 17(10), 1316–1318.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fortea, J., Sala-Llonch, R., Bartrés-Faz, D., et al. (2011). Cognitively preserved subjects with transitional cerebrospinal fluid ß-amyloid 1-42 values have thicker cortex in Alzheimer's disease vulnerable areas. Biological Psychiatry, 70(2), 183–190.

    Article  CAS  PubMed  Google Scholar 

  • Fripp, J., Bourgeat, P., Acosta, O., et al. (2008). Appearance modeling of 11C PiB PET images: Characterizing amyloid deposition in Alzheimer's disease, mild cognitive impairment and healthy aging. NeuroImage, 43(3), 430–439.

    Article  PubMed  Google Scholar 

  • Gidicsin, C. M., Maye, J. E., Locascio, J. J., et al. (2015). Cognitive activity relates to cognitive performance but not to Alzheimer disease biomarkers. Neurology, 85(1), 48–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gietl, A. F., Warnock, G., Riese, F., et al. (2015). Regional cerebral blood flow estimated by early PiB uptake is reduced in mild cognitive impairment and associated with age in an amyloid-dependent manner. Neurobiology of Aging, 36(4), 1619–1628.

    Article  PubMed  Google Scholar 

  • Goldman, W. P., Price, J. L., Storandt, M., et al. (2001). Absence of cognitive impairment or decline in preclinical Alzheimer’s disease. Neurology, 56, 361–367.

    Article  CAS  PubMed  Google Scholar 

  • Gu, Y., Razlighi, Q. R., Zahodne, L. B., et al. (2015). Brain amyloid deposition and longitudinal cognitive decline in Nondemented older subjects: Results from a multi-ethnic population. PloS One, 10(7), e0123743.

    Article  PubMed  PubMed Central  Google Scholar 

  • Hardy, J. A., & Higgins, G. A. (1992). Alzheimer’s disease: The amyloid cascade hypothesis. Science, 256, 184–185.

    Article  CAS  PubMed  Google Scholar 

  • Hardy, J., & Selkoe, D. J. (2002). The amyloid hypothesis of Alzheimer’s disease: Progress and problems on the road to therapeutics. Science, 297, 353–356.

    Article  CAS  PubMed  Google Scholar 

  • Harrington, K. D., Gould, E., Lim, Y. Y., et al. (2016). Amyloid burden and incident depressive symptoms in cognitively normal older adults. International Journal of Geriatric Psychiatry. Advance online publication. doi:10.1002/gps.4489.

    Google Scholar 

  • Hassenstab, J., Monsell, S. E., Mock, C., et al. (2015). Neuropsychological markers of cognitive decline in persons with Alzheimer disease neuropathology. J Neuropath Exp Neurol, 74, 1086–1092.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hassenstab, J., Chasse, R., Grabow, P., et al. (2016). Certified normal: Alzheimer’s disease biomarkers and normative estimates of cognitive functioning. Neurobiology of Aging, 43, 23–33.

    Article  PubMed  PubMed Central  Google Scholar 

  • Hatashita, S., & Yamasaki, H. (2010). Clinically different stages of Alzheimer's disease associated by amyloid deposition with [11C]-PIB PET imaging. Journal of Alzheimer’s Disease, 21(3), 995–1003.

    Article  PubMed  Google Scholar 

  • Hedden, T., Oh, H., Younger, A. P., & Patel, T. A. (2013). Meta-analysis of amyloid-cognition relations in cognitively normal older adults. Neurology, 80(14), 1341–1348.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hedges, L. V. (1981). Distribution theory for Glass's estimator of effect size and related estimators. Journal of Educational Statistics, 6(2), 107–128.

    Article  Google Scholar 

  • Hedges, L. V., & Vevea, J. L. (1998). Fixed- and random-effects models in meta-analysis. Psychological Methods, 4, 486–504.

    Article  Google Scholar 

  • Higgins, J. P. T., Thompson, S. G., Deeks, J. J., & Altman, D. G. (2003). Measuring inconsistency in meta-analysis. BMJ, 327, 557–560.

    Article  PubMed  PubMed Central  Google Scholar 

  • Holland, D., McEvoy, L. K., Desikan, R. S., et al. (2012). Enrichment and stratification for Predementia Alzheimer disease clinical trials. PloS One, 7(10), e47739.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hsu, P. J., Shou, H., Benzinger, T., et al. (2014). Amyloid burden in cognitively normal elderly is associated with preferential hippocampal subfield volume loss. Journal of Alzheimer’s Disease, 45(1), 27–33.

    Google Scholar 

  • Huijbers, W., Mormino, E. C., Wigman, S. E., et al. (2014). Amyloid deposition is linked to aberrant entorhinal activity among cognitively normal older adults. The Journal of Neuroscience, 34(15), 5200–5210.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Iturria-Medina, Y., Sotero, R. C., & Toussaint, P. J. (2016). Early role of vascular dysregulation on late-onset Alzheimer’s disease based on multifactorial data-driven analysis. Nature Communications, 7, article number: 11934.

  • Jack Jr., C. R., Knopman, D. S., Jagust, W. J., et al. (2010). Hypothetical model of dynamic biomarkers of the Alzheimer’s pathological cascade. Lancet Neurology, 9(1), 119–128.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jack Jr., C. R., Knopman, D. S., Weigand, S. D., et al. (2012). An operational approach to National Institute on Aging-Alzheimer's Association criteria for preclinical Alzheimer disease. Annals of Neurology, 71, 765–775.

    Article  PubMed  PubMed Central  Google Scholar 

  • Jack Jr., C. R., Knopman, D. S., Jagust, W. J., et al. (2013a). Update on hypothetical model of Alzheimer’s disease biomarkers. Lancet Neurology, 12(2), 207–216.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jack Jr., C. R., Wiste, H. J., Weigand, S. D., et al. (2013b). Amyloid-first and neurodegeneration-first profiles characterize incident amyloid PET positivity. Neurology, 81(20), 1732–1740.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jack Jr., C. R., Wiste, H. J., Weigand, S. D., et al. (2014). Age-specific population frequencies of cerebral β-amyloidosis and neurodegeneration among people with normal cognitive function aged 50-89 years: A cross-sectional study. Lancet Neurology, 13(10), 997–1005.

    Article  PubMed  Google Scholar 

  • Jansen, W. J., Ossenkoppele, R., Knol, D. L., Tijms, B. M., Scheltens, P., Verhey, F. R. J., Visser, P. J., & Amyloid Biomarker Study Group. (2015). Prevalence of cerebral amyloid pathology in persons without dementia: A meta-analysis. JAMA, 313(19), 1924–1938.

    Article  PubMed  PubMed Central  Google Scholar 

  • Jedynak, B. M., Lang, A., Liu, B., et al. (2012). A computational neurodegenerative diease progression score: Method and results with the Alzheimer’s Disease Neuroimaging Initiative cohort. NeuroImage, 63, 1478–1486.

    Article  PubMed  PubMed Central  Google Scholar 

  • Jessen, F., Amariglio, R. E., van Boxtel, M., et al. (2014). A conceptual framework for research on subjective cognitive decline in preclinical Alzheimer’s disease. Alzheimer’s & Dementia, 10, 844–852.

    Article  Google Scholar 

  • Knopman, D. S., Jack Jr., C. R., Wiste, H. J., et al. (2012). Short-term clinical outcomes for stages of NIA-AA preclinical Alzheimer disease. Neurology, 78(20), 1576–1582.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Knopman, D. S., Beiser, A., Machulda, M. M., et al. (2015). Spectrum of cognition short of dementia: Framingham heart study and Mayo Clinic study of aging. Neurology, 85, 1712–1721.

    Article  PubMed  PubMed Central  Google Scholar 

  • Lamar, M., Resnick, S. M., & Zonderman, A. B. (2003). Longitudinal changes in verbal memory in older adults. Neurology, 60, 82–86.

    Article  PubMed  Google Scholar 

  • Langbaum, J. B., Hendrix, S. B., Ayutyanont, N., et al. (2014). An empirically derived composite cognitive test score with improved power to track and evaluate treatments for preclinical Alzheimer’s disease. Alzheimer’s & Dementia, 10, 666–674.

    Article  Google Scholar 

  • Langbaum, J. B., Hendrix, S. B., Ayutyanont, N., et al. (2015). Establishing composite cognitive endpoints for use in preclinical Alzheimer’s disease trials. The Journal of Prevention of Alzheimer’s Disease, 2(1), 2–3.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Liberati, A., Altman, D. G., Tetzlaff, J., Mulrow, C., Gotzsche, P. C., Ioannidis, J. P. A., Moher, D. (2009). The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLOS Medicine, 6, e1000100.

  • Lim, H. K., Nebes, R., Snitz, B., et al. (2014). Regional amyloid burden and intrinsic connectivity networks in cognitively normal elderly subjects. Brain, 137, 3327–3338.

    Article  PubMed  PubMed Central  Google Scholar 

  • Lim, Y. Y., Maruff, P., Schindler, R., et al. (2015). Disruption of cholinergic neurotransmission exacerbates Aβ-related cognitive impairment in preclinical Alzheimer’s disease. Neurobiology of Aging, 36, 2709–2715.

    Article  CAS  PubMed  Google Scholar 

  • Lim, Y. Y., Snyder, P. J., Pietrzak, R. H., et al. (2016). Sensitivity of composite scores to amyloid burden in preclinical Alzheimer's disease: Introducing the Z-scores of attention, verbal fluency, and episodic memory for Nondemented older adults composite score. Alzheimer’s & Dementia, 2, 19–26.

    Google Scholar 

  • Llado-Saz, S., Atienzam, M., & Cantero, J. L. (2015). Increased levels of plasma amyloid-beta are related to cortical thinning and cognitive decline in cognitively normal elderly subjects. Neurobiology of Aging, 36(10), 2791–2797.

    Article  CAS  PubMed  Google Scholar 

  • Machulda, M. M., Hagen, C. E., Wiste, H. J., et al. (in press). Practice effects and longitudinal cognitive change in clinically normal older adutls differ by Alzheimer imaging biomarker status. The Clinical Neuropsychologist. doi:10.1080/13854046.2016.1241303.

  • Marchant, N. L., Reed, B. R., Sanossian, N., et al. (2013). The aging brain and cognition: Contribution of vascular injury and aβ to mild cognitive dysfunction. JAMA Neurology, 70(4), 488–495.

    Article  PubMed  PubMed Central  Google Scholar 

  • Mathis, C. A., Kuller, L. H., Klunk, W. E., et al. (2013). In vivo assessment of amyloid-β deposition in nondemented very elderly subjects. Annals of Neurology, 73, 751–761.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Molinuevo, J. L., Ripolles, P., Simó, M., et al. (2014). White matter changes in preclinical Alzheimer's disease: A magnetic resonance imaging-diffusion tensor imaging study on cognitively normal older people with positive amyloid β protein 42 levels. Neurobiology of Aging, 35(12), 2671–2680.

    Article  CAS  PubMed  Google Scholar 

  • Mormino, E. C., Brandel, M. G., Madison, C. M., et al. (2012). Not quite PIB-positive, not quite PIB-negative: Slight PIB elevations in elderly normal control subjects are biologically relevant. NeuroImage, 59, 1152–1160.

    Article  PubMed  Google Scholar 

  • Nelson, P. T., Alafuzoff, I., Bigio, E. H., Bouras, C., Braak, H., Cairns, N. J., et al. (2012). Correlation of Alzheimer disease neuropathologic changes with cognitive status: A review of the literature. Journal of Neuropathology & Experimental Neurology, 71, 362–381.

    Article  Google Scholar 

  • Oh, H., Mormino, E. C., Madison, C., et al. (2010). β-amyloid affects frontal and posterior brain networks in normal aging. NeuroImage, 54, 1887–1895.

    Article  PubMed  PubMed Central  Google Scholar 

  • Oh, H., Madison, C., Haight, T. J., et al. (2012). Effects of age and β-amyloid on cognitive changes in normal elderly people. Neurobiology of Aging, 33(12), 2746–2755.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Oh, H., Steffener, J., Razlighi, Q. R., et al. (2015). Aβ-related hyperactivation in frontoparietal control regions in cognitively normal elderly. Neurobiology of Aging, 36(12), 3247–3254.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Oh, H., Steffener, J., Razlighi, Q. R., et al. (2016). β-amyloid deposition is associated with decreased right prefrontal activation during task switching among cognitively normal elderly. Journal of Neuroscience, 36(6), 1962–1970.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ossenkoppele, R., Madison, C., Oh, H., et al. (2014). Is verbal episodic memory in elderly with amyloid deposits preserved through altered neuronal function? Cerebral Cortex, 24(8), 2210–2218.

    Article  PubMed  Google Scholar 

  • Petersen, R. C., Wiste, H. J., Weigand, S. D., et al. (2016). Association of Elevated Amyloid Levels with Cognition and Biomarkers in cognitively normal people from the community. JAMA Neurology, 73(1), 85–92.

    Article  PubMed  PubMed Central  Google Scholar 

  • Pike, K. E., Ellis, K. A., Villemagne, V. L., et al. (2011). Cognition and beta-amyloid in preclinical Alzheimer's disease: Data from the AIBL study. Neuropsychologia, 49(9), 2384–2390.

    Article  PubMed  Google Scholar 

  • Rentz, D. M., Locascio, J. J., Becker, J. A., et al. (2010). Cognition, reserve, and amyloid deposition in normal aging. Annals of Neurology, 67, 353–364.

    PubMed  Google Scholar 

  • Schott, J. M., Bartlett, J. W., Fox, N. C., & Barnes, J. (2010). Increased brain atrophy rates in cognitively normal older adults with low cerebrospinal fluid Aβ1-42. Annals of Neurology, 68(6), 825–834.

    Article  CAS  PubMed  Google Scholar 

  • Snitz, B. E., Weissfeld, L. A., Lopez, O. L., et al. (2013). Cognitive trajectories associated with β-amyloid deposition in the oldest-old without dementia. Neurology, 80(15), 1378–1384.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Soldan, A., Pettigrew, C., Cai, Q., et al. (2016). Hypothetical preclinical Alzheimer disease groups and longitudinal cognitive change. JAMA Neurology, 73(6), 698–705.

    Article  PubMed  PubMed Central  Google Scholar 

  • Sperling, R. A., Aisen, P. S., Beckett, L. A., et al. (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), 280–292.

    Article  Google Scholar 

  • Sperling, R. A., Johnson, K. A., Doraiswamy, P. M., et al. (2013). Amyloid deposition detected with florbetapir F 18 ((18)F-AV-45) is related to lower episodic memory performance in clinically normal older individuals. Neurobiology of Aging, 34(3), 822–831.

    Article  CAS  PubMed  Google Scholar 

  • Stark, S. L., Roe, C. M., Grant, E. A., et al. (2013). Preclinical Alzheimer disease and risk of falls. Neurology, 81, 437–443.

    Article  PubMed  PubMed Central  Google Scholar 

  • Susanto, T. A., Pua, E. P., & Zhou, J. (2015). Cognition, brain atrophy, and cerebrospinal fluid biomarkers changes from preclinical to dementia stage of Alzheimer's disease and the influence of apolipoprotein e. Journal of Alzheimer’s Disease, 45(1), 253–268.

    CAS  PubMed  Google Scholar 

  • Thai, C., Lim, Y. Y., Villemagne, V. L., et al. (2015). Amyloid-related memory decline in preclinical Alzheimer's disease is dependent on APOE ε4 and is detectable over 18-months. PloS One, 10(10), e0139082.

    Article  PubMed  PubMed Central  Google Scholar 

  • Vemuri, P., Lesnick, T. G., Przybelski, S. A., et al. (2015). Vascular and amyloid pathologies are independent predictors of cognitive decline in normal elderly. Brain, 138, 761–771.

    Article  PubMed  PubMed Central  Google Scholar 

  • Villemagne, V. L., Burnham, S., Bourgeat, P., et al. (2013). Amyloid β deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer's disease: A prospective cohort study. Lancet Neurology, 12(4), 357–367.

    Article  CAS  PubMed  Google Scholar 

  • Villeneuve, S., Reed, B. R., Wirth, M., et al. (2014). Cortical thickness mediates the effect of β-amyloid on episodic memory. Neurology, 82(9), 761–767.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Viola, K. L., & Klein, W. L. (2015). Amyloid B oligomers in Alzheimer’s disease pathogenesis, treatment, and diagnosis. Acta Neuropathologica, 129, 183–206.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vlassenko, A. G., McCue, L., Jasielec, M. S., et al. (2016). Imaging and cerebrospinal fluid biomarkers in early preclinical alzheimer disease. Annals of Neurology, 80(3), 379–387.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Voevodskaya, O., Sundgren, P. C., Strandberg, O., et al. (2016). Myo-inositol changes precede amyloid pathology and relate to APOE genotype in Alzheimer disease. Neurology, 86(19), 1754–1761.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vos, S. J., Xiong, C., Visser, P. J., et al. (2013). Preclinical Alzheimer's disease and its outcome: A longitudinal cohort study. Lancet Neurology, 12(10), 957–965.

    Article  PubMed  PubMed Central  Google Scholar 

  • Vos, S. J., Gordon, B. A., Su, Y., et al. (2016). NIA-AA staging of preclinical Alzheimer disease: Discordance and concordance of CSF and imaging biomarkers. Neurobiology of Aging, 44, 1–8.

    Article  PubMed  PubMed Central  Google Scholar 

  • Wirth, M., Madison, C. M., Rabinovici, G. D., et al. (2013a). Alzheimer’s disease neurodegenerative biomarkers are associated with decreased cognitive function but not β-amyloid in cognitively normal older individuals. Neurobiology of Disease, 33(13), 5553–5563.

    CAS  Google Scholar 

  • Wirth, M., Oh, H., Mormino, E. C., et al. (2013b). The effect of amyloid β on cognitive decline is modulated by neural integrity in cognitively normal elderly. Alzheimer’s & Dementia, 9(6), 687–698.

    Article  Google Scholar 

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Acknowledgments

SDH is supported by National Institute on Aging grant K23AG040625, and the American Federation for Aging Research (AFAR). NHS serves as a consultant to Biogen. The funding agencies had no role in this study.

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Authors and Affiliations

  1. Department of Family Medicine, USC Keck School of Medicine, 1000 S. Fremont Avenue, Unit 22, HSA Building A-6, 4th Floor, Room 6437A, Alhambra, CA, 91803, USA

    S. Duke Han & Caroline P. Nguyen

  2. Department of Neurology, USC Keck School of Medicine, Los Angeles, CA, USA

    S. Duke Han

  3. Department of Psychology, USC Dornsife College, Los Angeles, CA, USA

    S. Duke Han & Daniel A. Nation

  4. USC School of Gerontology, Los Angeles, CA, USA

    S. Duke Han

  5. Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA

    Nikki H. Stricker

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  1. S. Duke Han
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Correspondence to S. Duke Han.

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A correction to this article is available online at https://doi.org/10.1007/s11065-017-9366-0.

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Duke Han, S., Nguyen, C.P., Stricker, N.H. et al. Detectable Neuropsychological Differences in Early Preclinical Alzheimer’s Disease: A Meta-Analysis. Neuropsychol Rev 27, 305–325 (2017). https://doi.org/10.1007/s11065-017-9345-5

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