APOE E4 Carriers Show Prospective Memory Enhancement Under Nicotine, and Evidence for Specialisation Within Medial BA10

There is evidence to suggest that the APOE ɛ4 allele (which confers an increased risk of developing dementia) might be associated with cognitive advantages earlier in life. Further, nicotine might selectively benefit ɛ4 carriers. We used fMRI to explore performance on a prospective memory (PM) task in young adults (age 18–30) with and without nicotine using a within-subjects design. Participants performed an ongoing task while retaining a PM instruction to respond to specific stimuli embedded in the task. Nicotine effects varied according to APOE status. Reaction times to the PM cue were improved under nicotine in ɛ4 carriers, but not in ɛ3 carriers. In an event-related analysis, extrastriate responses to PM trials were enhanced by nicotine only in ɛ4 carriers. These differences in early visual processing may contribute to the behavioral findings. Activity in medial BA10 (previously implicated in PM) differentiated ɛ4 from ɛ3 carriers. One BA10 subregion showed greater deactivation in ɛ4 carriers during PM trials. Activity in other BA10 subregions was modulated by PM reaction time, pointing to region-specific effects within medial BA10. In addition, activity in right hippocampal formation was only seen in ɛ4 carriers receiving nicotine. These results demonstrate that cognitive enhancement by nicotine can selectively benefit APOE ɛ4 carriers, and point to genotype-specific differences in neural activity during PM. In addition, these results show that the role of medial BA10 in PM likely involves varying contributions from functionally specific subregions.

[1]  Raja Parasuraman,et al.  Scaling of visuospatial attention undergoes differential longitudinal change as a function of APOE genotype prior to old age: results from the NIMH BIOCARD study. , 2005, Neuropsychology.

[2]  Angela J. Yu,et al.  Uncertainty, Neuromodulation, and Attention , 2005, Neuron.

[3]  S. Scott,et al.  The role of the rostral frontal cortex (area 10) in prospective memory: a lateral versus medial dissociation , 2003, Neuropsychologia.

[4]  K. Zilles,et al.  Nicotine Modulates Reorienting of Visuospatial Attention and Neural Activity in Human Parietal Cortex , 2005, Neuropsychopharmacology.

[5]  Gereon R. Fink,et al.  fMRI Data Predict Individual Differences of Behavioral Effects of Nicotine: A Partial Least Square Analysis , 2007, Journal of Cognitive Neuroscience.

[6]  J. Rusted,et al.  Prospective memory or prospective attention: physiological and pharmacological support for an attentional model. , 2008, The international journal of neuropsychopharmacology.

[7]  Scott T. Grafton,et al.  Wandering Minds: The Default Network and Stimulus-Independent Thought , 2007, Science.

[8]  Anna-Lisa Cohen,et al.  Separable brain systems supporting cued versus self-initiated realization of delayed intentions. , 2009, Journal of experimental psychology. Learning, memory, and cognition.

[9]  K. Fagerström,et al.  Clinical Pharmacokinetics of Nasal Nicotine Delivery , 1996, Clinical pharmacokinetics.

[10]  T. Allison,et al.  Modulation of human extrastriate visual processing by selective attention to colours and words. , 1998, Brain : a journal of neurology.

[11]  S. Gauthier,et al.  Apolipoprotein E4 allele as a predictor of cholinergic deficits and treatment outcome in Alzheimer disease. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[12]  J. Rusted,et al.  Nicotine improves memory for delayed intentions , 2005, Psychopharmacology.

[13]  S J Heishman,et al.  Effect of nicotine on brain activation during performance of a working memory task , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[14]  Mark S. Cohen,et al.  Patterns of brain activation in people at risk for Alzheimer's disease. , 2000, The New England journal of medicine.

[15]  Veena Kumari,et al.  Cognitive effects of nicotine in humans: an fMRI study , 2003, NeuroImage.

[16]  G. Fink,et al.  Effects of the cholinergic agonist nicotine on reorienting of visual spatial attention and top-down attentional control , 2008, Neuroscience.

[17]  Mark A McDaniel,et al.  Brain regions and their dynamics in prospective memory retrieval: a MEG study. , 2007, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[18]  Mark W. Bondi,et al.  Revision of the apolipoprotein E compensatory mechanism recruitment hypothesis , 2008, Alzheimer's & Dementia.

[19]  S. Stone-Elander,et al.  Cerebral effects of nicotine during cognition in smokers and non-smokers , 1998, Psychopharmacology.

[20]  J. Pitha,et al.  A Possible Role of Apolipoprotein E Polymorphism in Predisposition to Higher Education , 2001, Neuropsychobiology.

[21]  R. Dolan,et al.  Cholinergic modulation of cognition: Insights from human pharmacological functional neuroimaging , 2011, Progress in Neurobiology.

[22]  Eliot Hazeltine,et al.  Dissociable Contributions of Prefrontal and Parietal Cortices to Response Selection , 2002, NeuroImage.

[23]  Paul M. Matthews,et al.  Differential effects of the APOE genotype on brain function across the lifespan , 2011, NeuroImage.

[24]  J. Rusted,et al.  Acute effects of nicotine administration during prospective memory, an event related fMRI study , 2011, Neuropsychologia.

[25]  Lars T Westlye,et al.  Increased Hippocampal Default Mode Synchronization during Rest in Middle-Aged and Elderly APOE ε4 Carriers: Relationships with Memory Performance , 2011, The Journal of Neuroscience.

[26]  S. Tsai,et al.  Intelligence and event-related potentials for young female human volunteer apolipoprotein E epsilon4 and non-epsilon4 carriers. , 2000, Neuroscience letters.

[27]  Karl J. Friston,et al.  Stochastic Designs in Event-Related fMRI , 1999, NeuroImage.

[28]  J. Rusted,et al.  Positive effects of nicotine on cognition: the deployment of attention for prospective memory , 2008, Psychopharmacology.

[29]  R. Parasuraman,et al.  Effects of apolipoprotein E genotype on spatial attention, working memory, and their interaction in healthy, middle-aged adults: results From the National Institute of Mental Health's BIOCARD study. , 2005, Neuropsychology.

[30]  Amy L. Shelton,et al.  Altered medial temporal lobe responses during visuospatial encoding in healthy APOE*4 carriers , 2008, Neurobiology of Aging.

[31]  Ira Driscoll,et al.  Apolipoprotein E and prospective memory in normally aging adults. , 2005, Neuropsychology.

[32]  E. Stein,et al.  Cognitive Mechanisms of Nicotine on Visual Attention , 2002, Neuron.

[33]  S. Tsai,et al.  Intelligence and event-related potentials for young female human volunteer apolipoprotein E ε4 and non-ε4 carriers , 2000, Neuroscience Letters.

[34]  Richard B. Buxton,et al.  Resting-state BOLD networks versus task-associated functional MRI for distinguishing Alzheimer's disease risk groups , 2009, NeuroImage.

[35]  Simon B. Eickhoff,et al.  A new SPM toolbox for combining probabilistic cytoarchitectonic maps and functional imaging data , 2005, NeuroImage.

[36]  C. Frith,et al.  Brain regions involved in prospective memory as determined by positron emission tomography , 2001, Neuropsychologia.

[37]  Ian J. Deary,et al.  Cognitive change and the APOE epsilon 4 allele. , 2002 .

[38]  Eric Nyberg,et al.  Nicotine effects on default mode network during resting state , 2011, Psychopharmacology.

[39]  Effects of scopolamine on verbal memory; a retrieval or acquisition deficit? , 1989, Neuropsychobiology.

[40]  Lisa T. Eyler,et al.  Verbal paired-associate learning by APOE genotype in non-demented older adults: fMRI evidence of a right hemispheric compensatory response , 2007, Neurobiology of Aging.

[41]  L. Murri,et al.  Causative and susceptibility genes for Alzheimer’s disease: a review , 2003, Brain Research Bulletin.

[42]  P. Burgess,et al.  Functional neuroimaging studies of prospective memory: What have we learnt so far? , 2011, Neuropsychologia.

[43]  Caroline Hayward,et al.  Ageing: Cognitive change and the APOE ɛ4 allele , 2002, Nature.

[44]  M. Schölvinck,et al.  Differential components of prospective memory? Evidence from fMRI , 2006, Neuropsychologia.

[45]  Clare E. Mackay,et al.  The effects of APOE-ε4 on the BOLD response , 2012, Neurobiology of Aging.

[46]  W. Gehring,et al.  More attention must be paid: The neurobiology of attentional effort , 2006, Brain Research Reviews.

[47]  Iroise Dumontheil,et al.  Function and localization within rostral prefrontal cortex (area 10) , 2007, Philosophical Transactions of the Royal Society B: Biological Sciences.

[48]  Yihong Yang,et al.  Nicotine Enhances Visuospatial Attention by Deactivating Areas of the Resting Brain Default Network , 2007, The Journal of Neuroscience.

[49]  P. Matthews,et al.  Distinct patterns of brain activity in young carriers of the APOE e4 allele , 2009, NeuroImage.

[50]  Paul S Tofts,et al.  MRI of carriers of the apolipoprotein E e4 allele–evidence for structural differences in normal‐appearing brain tissue in e4+ relative to e4– young adults , 2013, NMR in biomedicine.

[51]  Peter Boesiger,et al.  Better memory and neural efficiency in young apolipoprotein E epsilon4 carriers. , 2007, Cerebral cortex.

[52]  Mark D'Esposito,et al.  Goal-directed attention alters the tuning of object-based representations in extrastriate cortex , 2012, Front. Hum. Neurosci..

[53]  T. Arendt,et al.  Plastic neuronal remodeling is impaired in patients with Alzheimer's disease carrying apolipoprotein epsilon 4 allele. , 1997, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[54]  H. Braak,et al.  Diagnostic Criteria for Neuropathologic Assessment of Alzheimer’s Disease , 1997, Neurobiology of Aging.

[55]  J. Jia,et al.  Meta-analysis of APOE4 allele and outcome after traumatic brain injury. , 2008, Journal of neurotrauma.

[56]  Sachin Dixit,et al.  APOE4 Allele Disrupts Resting State fMRI Connectivity in the Absence of Amyloid Plaques or Decreased CSF Aβ42 , 2010, The Journal of Neuroscience.

[57]  Naji Tabet,et al.  Positive Effects of Cholinergic Stimulation Favor Young APOE ɛ4 Carriers , 2010, Neuropsychopharmacology.

[58]  D. Delis,et al.  APOE genotype is associated with left-handedness and visuospatial skills in children , 2010, Neurobiology of Aging.

[59]  Hillary C. M. Nelson.  The National Adult Reading Test , 1982 .

[60]  Clare E. Mackay,et al.  The effects of APOE on brain activity do not simply reflect the risk of Alzheimer's disease , 2012, Neurobiology of Aging.

[61]  Jared Stokes,et al.  Temporal lobe functional activity and connectivity in young adult APOE ɛ4 carriers , 2010, Alzheimer's & Dementia.

[62]  Peter Boesiger,et al.  Better Memory and Neural Efficiency in Young Apolipoprotein E ε4 Carriers , 2007 .

[63]  J. Haxby,et al.  Cholinergic enhancement and increased selectivity of perceptual processing during working memory. , 2000, Science.

[64]  M. Goldberg,et al.  Attention, intention, and priority in the parietal lobe. , 2010, Annual review of neuroscience.

[65]  R. Mahley,et al.  Apolipoprotein E: cholesterol transport protein with expanding role in cell biology. , 1988, Science.

[66]  R. Parasuraman,et al.  The apolipoprotein E gene, attention, and brain function. , 2002, Neuropsychology.

[67]  Yaakov Stern,et al.  fMRI evidence of compensatory mechanisms in older adults at genetic risk for Alzheimer disease , 2005, Neurology.

[68]  Vinod Menon,et al.  Functional connectivity in the resting brain: A network analysis of the default mode hypothesis , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[69]  L. Castro,et al.  Prospective memory and mesial temporal epilepsy associated with hippocampal sclerosis , 2008, Neuropsychologia.

[70]  Clare E. Mackay,et al.  The effects of APOE on the functional architecture of the resting brain , 2012, NeuroImage.