Longitudinal modeling of frontal cognition in APOE ε4 homozygotes, heterozygotes, and noncarriers

被引:77
作者
Caselli, R. J. [1 ,6 ]
Dueck, A. C. [2 ]
Locke, D. E. C. [3 ,6 ]
Hoffman-Snyder, C. R. [1 ,6 ]
Woodruff, B. K. [1 ,6 ]
Rapcsak, S. Z. [4 ,6 ,7 ]
Reiman, E. M. [5 ,6 ]
机构
[1] Mayo Clin Arizona, Dept Neurol, Scottsdale, AZ 85259 USA
[2] Mayo Clin Arizona, Dept Biostat, Scottsdale, AZ 85259 USA
[3] Mayo Clin Arizona, Dept Psychol, Scottsdale, AZ 85259 USA
[4] Univ Arizona, Dept Neurol, Tucson, AZ USA
[5] Univ Arizona, Dept Psychiat, Tucson, AZ USA
[6] Arizona Alzheimers Res Consortium, Phoenix, AZ USA
[7] So Arizona VA Hlth Care Syst, Tucson, AZ USA
关键词
AMYLOID-BETA-PEPTIDE; ALZHEIMERS-DISEASE; EXECUTIVE CONTROL; DECLINE; TAU; IMPAIRMENT; TOXICITY; LESIONS; BEGINS; ALLELE;
D O I
10.1212/WNL.0b013e3182167147
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Background: Fibrillar amyloid deposition preferentially affects the frontal lobes, temporal pole/neocortex, and posterior cingulate by age 65 years in APOE epsilon 4 carriers prior to the diagnosis of mild cognitive impairment (MCI) and Alzheimer disease (AD), but is it impairing frontally mediated neuropsychological performance? Methods: A total of 71 epsilon 4 homozygotes (HMZ), 194 epsilon 4 heterozygotes (HTZ), and 356 epsilon 4 noncarriers (NC) who did not differ significantly in mean age (56.6 years), years of education (15.6), gender (70% women), or follow-up duration (6.3 years) had neuropsychological testing every 2 years including the Auditory Verbal Learning Test (AVLT) and frontal/executive tasks sensitive to psychomotor speed, working memory, problem solving, and activity. A subset also received the Iowa Gambling Task (IGT). Findings were then tested in a clinical sample of 27 patients with incident MCI and AD. Results: APOE epsilon 4 carriers had greater acceleration of decline (quadratic effect) than NC on the AVLT (p = 0.04) but not on any frontal test. APOE epsilon 4 HMZ had greater velocity of decline (linear effects) than NC on all mental arithmetic tests: paced auditory serial attention task (PASAT) 3 second (p = 0.01) and 2 second (p = 0.004) versions; and Wechsler Adult Intelligence Scale-Revised arithmetic (p = 0.048). IGT performance did not differ between 12 epsilon 4 HMZ, 27 epsilon 4 HTZ, and 44 NC. Among 27 patients with incident MCI and AD, the PASAT showed progressive decline preceding diagnosis in 50%. Conclusions: No frontal cognitive effects were as robust as memory decline. APOE epsilon 4 HMZ declined more quickly than NC on mental arithmetic tests related to frontal lobe-mediated working memory ability. Neurology (R) 2011; 76: 1383-1388
引用
收藏
页码:1383 / 1388
页数:6
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