Andrew J Saykin

Publications (265) View all

• Article: Dysexecutive and amnesic AD subtypes defined by single indicator and modern psychometric approaches: relationships with SNPs in ADNI.

  Shubhabrata Mukherjee, Emily Trittschuh, Laura E Gibbons, R Scott Mackin, Andrew Saykin, Paul K Crane
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  ABSTRACT: Previous investigators have suggested the existence of distinct cognitive phenotypes of Alzheimer's disease (AD): a dysexecutive subgroup with executive functioning worse than memory and an amnesic subgroup with memory worse than executive functioning. We evaluated data from the AD Neuroimaging Initiative. We assigned people with AD to dysexecutive and amnesic subgroups using single indicators, and analogously using the ADNI-Mem and ADNI-EF composite scores developed using modern psychometric approaches. We evaluated associations between subgroup membership, APOE genotype, and single nucleotide polymorphisms (SNPs) are associated with AD, and brain vascular disease defined as white matter hyperintensities (WMH) and MRI-identified infarcts. We hypothesized that APOE ε4 and alleles associated with higher risk for AD would predict amnesic subgroup membership; alleles associated with higher WMH or infarct burden would predict dysexecutive subgroup membership. Classification agreement between the two approaches was only fair (kappa = 0.23). There was no relationship between APOE alleles and the dysexecutive or amnesic phenotypes defined by either categorization approach. There were 58 AD-related and 25 WMH- or infarct-related SNPs for which odds ratios were > 1.5 or < 0.67 for dysexecutive vs. amnesic subgroup defined by either categorization approach. Higher proportions of SNPs had odds ratios in the hypothesized direction for the subgroups defined by the modern psychometric approach for AD-related (58 % vs. 38 %, p-value < 0.001) and brain vascular disease-related SNPs (48 vs. 32 %, p-value = 0.01). Genetic variation may underlie differential performance in memory and executive functioning among people with AD. Modern psychometric composite scores produced group assignments with more SNP associations in the hypothesized direction.
  Brain Imaging and Behavior 11/2012; · 1.66 Impact Factor
• Article: Advanced cognitive training for breast cancer survivors: a randomized controlled trial.

  Diane Von Ah, Janet S Carpenter, Andrew Saykin, Patrick Monahan, Jingwei Wu, Menggang Yu, George Rebok, Karlene Ball, Bryan Schneider, Michael Weaver, Eileen Tallman, Fred Unverzagt
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  ABSTRACT: The purpose of this study was to evaluate the preliminary efficacy and satisfaction/acceptability of training in memory or speed of processing versus wait-list control for improving cognitive function in breast cancer survivors. 82 breast cancer survivors completed a three-group randomized, controlled trial. Primary outcomes were objective neuropsychological tests of memory and speed of processing. Secondary outcomes were perceived cognitive functioning, symptom distress (mood disturbance, anxiety, and fatigue), quality of life, and intervention satisfaction/acceptability. Data were collected at baseline, post-intervention, and 2-month follow-up. Using repeated-measures mixed-linear ANCOVA models, each intervention was compared to wait-list control while adjusting for age, education, and baseline measures. The effect sizes for differences in means and the reliable improvement percentage were reported. The results show that domain-specific effects were seen for both interventions: memory training improved memory performance at 2-month follow-up (p = 0.036, d = 0.59); speed of processing training improved processing speed post-intervention (p = 0.040, d = 0.55) and 2-month follow-up (p = 0.016; d = 0.67). Transfer effects to non-trained domains were seen for speed of processing training with improved memory post-intervention (p = 0.007, d = 0.75) and 2-month follow-up (p = 0.004, d = 0.82). Both interventions were associated with improvements in perceived cognitive functioning, symptom distress, and quality of life. Ratings of satisfaction/acceptability were high for both interventions. It was concluded that while both interventions appeared promising, speed of processing training resulted in immediate and durable improvements in objective measures of processing speed and verbal memory. Speed of processing training may have broader benefits in this clinical population.
  Breast Cancer Research and Treatment 08/2012; 135(3):799-809. · 4.43 Impact Factor
• Conference Proceeding: Common gene networks underlying memory impairment: A comparison of pathway analysis methods in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort

  Vijay Ramanan, Sungeun Kim, Kelly Holohan, Li Shen, Kwangsik Ngo, Shannon Risacher, Tatiana Foroud, Shubhabrata Mukherjee, Paul Crane, Paul Aisen, Ronald Petersen, Michael Weiner, Andrew Saykin, Alzheimer's Disease Neuroimaging Initiative
  Alzheimer’s Association International Conference on Alzheimer’s Disease (AAIC), Vancouver, Canada; 07/2012
• Source

  Available from: Trygve Bakken

  Article: Association between mitochondrial DNA variations and Alzheimer's disease in the ADNI cohort.

  Anita Lakatos, Olga Derbeneva, Danny Younes, David Keator, Trygve Bakken, Maria Lvova, Marty Brandon, Guia Guffanti, Dora Reglodi, Andrew Saykin, Michael Weiner, Fabio Macciardi, Nicholas Schork, Douglas C Wallace, Steven G Potkin
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  ABSTRACT: Despite the central role of amyloid deposition in the development of Alzheimer's disease (AD), the pathogenesis of AD still remains elusive at the molecular level. Increasing evidence suggests that compromised mitochondrial function contributes to the aging process and thus may increase the risk of AD. Dysfunctional mitochondria contribute to reactive oxygen species (ROS) which can lead to extensive macromolecule oxidative damage and the progression of amyloid pathology. Oxidative stress and amyloid toxicity leave neurons chemically vulnerable. Because the brain relies on aerobic metabolism, it is apparent that mitochondria are critical for the cerebral function. Mitochondrial DNA sequence changes could shift cell dynamics and facilitate neuronal vulnerability. Therefore we postulated that mitochondrial DNA sequence polymorphisms may increase the risk of AD. We evaluated the role of mitochondrial haplogroups derived from 138 mitochondrial polymorphisms in 358 Caucasian Alzheimer's Disease Neuroimaging Initiative (ADNI) subjects. Our results indicate that the mitochondrial haplogroup UK may confer genetic susceptibility to AD independently of the apolipoprotein E4 (APOE4) allele.
  Neurobiology of aging 08/2010; 31(8):1355-63. · 5.94 Impact Factor
• Article: Voxel and surface-based topography of memory and executive deficits in mild cognitive impairment and Alzheimer's disease.

  Kwangsik Nho, Shannon L Risacher, Paul K Crane, Charles Decarli, M Maria Glymour, Christian Habeck, Sungeun Kim, Grace J Lee, Elizabeth Mormino, Shubhabrata Mukherjee, Li Shen, John D West, Andrew J Saykin
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  ABSTRACT: Mild cognitive impairment (MCI) and Alzheimer's disease (AD) are associated with a progressive loss of cognitive abilities. In the present report, we assessed the relationship of memory and executive function with brain structure in a sample of 810 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants, including 188 AD, 396 MCI, and 226 healthy older adults (HC). Composite scores of memory (ADNI-Mem) and executive function (ADNI-Exec) were generated by applying modern psychometric theory to item-level data from ADNI's neuropsychological battery. We performed voxel-based morphometry (VBM) and surface-based association (SurfStat) analyses to evaluate relationships of ADNI-Mem and ADNI-Exec with grey matter (GM) density and cortical thickness across the whole brain in the combined sample and within diagnostic groups. We observed strong associations between ADNI-Mem and medial and lateral temporal lobe atrophy. Lower ADNI-Exec scores were associated with advanced GM and cortical atrophy across broadly distributed regions, most impressively in the bilateral parietal and temporal lobes. We also evaluated ADNI-Exec adjusted for ADNI-Mem, and found associations with GM density and cortical thickness primarily in the bilateral parietal, temporal, and frontal lobes. Within-group analyses suggest these associations are strongest in patients with MCI and AD. The present study provides insight into the spatially unbiased associations between brain atrophy and memory and executive function, and underscores the importance of structural brain changes in early cognitive decline.
  Brain Imaging and Behavior 10/2012; · 1.66 Impact Factor