Functional Neural Correlates of Attentional Deficits in Amnestic Mild Cognitive Impairment

Although amnestic mild cognitive impairment (aMCI; often considered a prodromal phase of Alzheimer’s disease, AD) is most recognized by its implications for decline in memory function, research suggests that deficits in attention are present early in aMCI and may be predictive of progression to AD. The present study used functional magnetic resonance imaging to examine differences in the brain during the attention network test between 8 individuals with aMCI and 8 neurologically healthy, demographically matched controls. While there were no significant behavioral differences between groups for the alerting and orienting functions, patients with aMCI showed more activity in neural regions typically associated with the networks subserving these functions (e.g., temporoparietal junction and posterior parietal regions, respectively). More importantly, there were both behavioral (i.e., greater conflict effect) and corresponding neural deficits in executive control (e.g., less activation in the prefrontal and anterior cingulate cortices). Although based on a small number of patients, our findings suggest that deficits of attention, especially the executive control of attention, may significantly contribute to the behavioral and cognitive deficits of aMCI.

[1]  J. Foster Selective attention in Alzheimer's disease. , 2001, Frontiers in bioscience : a journal and virtual library.

[2]  R. Davidson,et al.  The integration of negative affect, pain and cognitive control in the cingulate cortex , 2011, Nature Reviews Neuroscience.

[3]  E. Duchesnay,et al.  Longitudinal brain metabolic changes from amnestic Mild Cognitive Impairment to Alzheimer's disease , 2009, NeuroImage.

[4]  M. Rapp,et al.  Attention and executive control predict Alzheimer disease in late life: results from the Berlin Aging Study (BASE). , 2005, The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry.

[5]  J. Kaye,et al.  Attention deficit in Alzheimer's disease is not simulated by an anticholinergic/antihistaminergic drug and is distinct from deficits in healthy aging , 1994, Neurology.

[6]  C. Bottino,et al.  Cognitive intervention in amnestic Mild Cognitive Impairment: A systematic review , 2012, Neuroscience & Biobehavioral Reviews.

[7]  Kuncheng Li,et al.  Visual attention deficits in Alzheimer's disease: an fMRI study , 2005, Neuroscience Letters.

[8]  B Horwitz,et al.  Longitudinal study of the early neuropsychological and cerebral metabolic changes in dementia of the Alzheimer type. , 1988, Journal of clinical and experimental neuropsychology.

[9]  N Butters,et al.  Detection and staging of dementia in Alzheimer's disease. Use of the neuropsychological measures developed for the Consortium to Establish a Registry for Alzheimer's Disease. , 1992, Archives of neurology.

[10]  M. Corbetta,et al.  Control of goal-directed and stimulus-driven attention in the brain , 2002, Nature Reviews Neuroscience.

[11]  P. Johannsen,et al.  Cortical Responses to Sustained and Divided Attention in Alzheimer's Disease , 1999, NeuroImage.

[12]  Maria Victoria Sebastian,et al.  Attentional Dysfunction of the Central Executive in Ad: Evidence from Dual Task and Perseveration Errors , 2006, Cortex.

[13]  S. Petersen,et al.  A dual-networks architecture of top-down control , 2008, Trends in Cognitive Sciences.

[14]  Lars Bäckman,et al.  Cognitive impairment in preclinical Alzheimer's disease: a meta-analysis. , 2005, Neuropsychology.

[15]  Bruce D. McCandliss,et al.  Testing the Efficiency and Independence of Attentional Networks , 2002, Journal of Cognitive Neuroscience.

[16]  J. Haxby,et al.  Attention and brain function in Alzheimer's disease: A review. , 1993 .

[17]  Efstathios D. Gennatas,et al.  Divergent network connectivity changes in behavioural variant frontotemporal dementia and Alzheimer's disease. , 2010, Brain : a journal of neurology.

[18]  Keith A. Johnson,et al.  MRI-guided SPECT perfusion measures and volumetric MRI in prodromal Alzheimer disease. , 2003, Archives of neurology.

[19]  Benjamin J. Shannon,et al.  Molecular, Structural, and Functional Characterization of Alzheimer's Disease: Evidence for a Relationship between Default Activity, Amyloid, and Memory , 2005, The Journal of Neuroscience.

[20]  M. Sano Neuropsychological Testing in the Diagnosis of Dementia , 2006, Journal of geriatric psychiatry and neurology.

[21]  R Bucks,et al.  Attention and fluctuating attention in patients with dementia with Lewy bodies and Alzheimer disease. , 2001, Archives of neurology.

[22]  Eric Salmon,et al.  Metabolic correlates of clinical heterogeneity in questionable Alzheimer's disease , 2008, Neurobiology of Aging.

[23]  J. Haxby,et al.  Longitudinal study of cerebral metabolic asymmetries and associated neuropsychological patterns in early dementia of the Alzheimer type. , 1990, Archives of neurology.

[24]  D. Perani,et al.  MCI conversion to dementia and the APOE genotype , 2004, Neurology.

[25]  S. Folstein,et al.  "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. , 1975, Journal of psychiatric research.

[26]  J. Cummings,et al.  Executive control function: a review of its promise and challenges for clinical research. A report from the Committee on Research of the American Neuropsychiatric Association. , 2002, The Journal of neuropsychiatry and clinical neurosciences.

[27]  Brian R Ott,et al.  Interactions between phasic alerting and spatial orienting: effects of normal aging and Alzheimer's disease. , 2004, Neuropsychology.

[28]  Diego Fernandez-Duque,et al.  Attentional networks in normal aging and Alzheimer's disease. , 2006, Neuropsychology.

[29]  S. Rombouts,et al.  Altered resting state networks in mild cognitive impairment and mild Alzheimer's disease: An fMRI study , 2005, Human brain mapping.

[30]  R. Buckner,et al.  Functional-Anatomic Fractionation of the Brain's Default Network , 2010, Neuron.

[31]  R. Petersen,et al.  Mild cognitive impairment , 2006, The Lancet.

[32]  A. Baddeley,et al.  Attentional control in Alzheimer's disease. , 2001, Brain : a journal of neurology.

[33]  David A. Balota,et al.  Inhibition of Return and Visuospatial Attention in Healthy Older Adults and Individuals With Dementia of the Alzheimer Type , 1997 .

[34]  M. Mandelkern,et al.  Executive deficits and regional brain metabolism in Alzheimer's disease , 2010, International journal of geriatric psychiatry.

[35]  P. Cras,et al.  RECENT DEVELOPMENTS IN ALZHEIMER’S DISEASE , 2001, Acta clinica Belgica.

[36]  M. Posner,et al.  Cognitive and emotional influences in anterior cingulate cortex , 2000, Trends in Cognitive Sciences.

[37]  H. Möller,et al.  Functional connectivity of the fusiform gyrus during a face-matching task in subjects with mild cognitive impairment. , 2006, Brain : a journal of neurology.

[38]  D. Bennett,et al.  Vitamin E and donepezil for the treatment of mild cognitive impairment. , 2005, The New England journal of medicine.

[39]  Jin Fan,et al.  Searching for the Majority: Algorithms of Voluntary Control , 2008, PloS one.

[40]  R. de Raedt,et al.  Attentional processes discriminate between patients with mild Alzheimer's disease and cognitively healthy elderly , 2006, International Psychogeriatrics.

[41]  J. Hodges,et al.  The nature and staging of attention dysfunction in early (minimal and mild) Alzheimer’s disease: relationship to episodic and semantic memory impairment , 2000, Neuropsychologia.

[42]  Eric Salmon,et al.  Executive Dysfunction in Alzheimer's Disease , 1999, Cortex.

[43]  J. Price,et al.  Mild cognitive impairment represents early-stage Alzheimer disease. , 2001, Archives of neurology.

[44]  Tianzi Jiang,et al.  Changes in hippocampal connectivity in the early stages of Alzheimer's disease: Evidence from resting state fMRI , 2006, NeuroImage.

[45]  J. Hart,et al.  Distinct prefrontal cortex activity associated with item memory and source memory for visual shapes. , 2003, Brain research. Cognitive brain research.

[46]  A. Tales,et al.  Alerting and orienting in Alzheimer's disease. , 2006, Neuropsychology.

[47]  J V Haxby,et al.  Visuospatial attention in dementia of the Alzheimer type. , 1992, Brain : a journal of neurology.

[48]  Considering phasic alerting in Alzheimer's disease: comment on Tales et al. (2006). , 2006, Neuropsychology.

[49]  C. Marra,et al.  Predictors of Cognitive Decline in the Early Stage of Probable Alzheimer’s Disease , 2000, Dementia and Geriatric Cognitive Disorders.

[50]  D. Stuss,et al.  Visual attention deficits in Alzheimer's disease: simple versus conjoined feature search. , 1999, Neuropsychology.

[51]  B L Holman,et al.  Preclinical prediction of Alzheimer's disease using SPECT , 1998, Neurology.

[52]  J. Pardo,et al.  Attentional Mechanisms , 2022 .

[53]  K Ball,et al.  Visual attention impairments in Alzheimer’s disease , 2000, Neurology.

[54]  E. Warriner,et al.  Balancing the Need for Reliability and Time Efficiency: Short Forms of the Wechsler Adult Intelligence Scale-III , 2004 .

[55]  Jin Fan,et al.  Testing the behavioral interaction and integration of attentional networks , 2009, Brain and Cognition.

[56]  Giovanni Giulietti,et al.  Damage to the cingulum contributes to alzheimer's disease pathophysiology by deafferentation mechanism , 2012, Human brain mapping.

[57]  Marco Rabuffetti,et al.  Specific Impairments of Selective Attention in Mild Alzheimer’s Disease , 2005, Journal of clinical and experimental neuropsychology.

[58]  J. Cummings,et al.  Executive Control Function , 2002 .

[59]  J. Morris The Clinical Dementia Rating (CDR) , 1993, Neurology.

[60]  E Magni,et al.  Executive dysfunction in early Alzheimer's disease. , 1996, Journal of neurology, neurosurgery, and psychiatry.

[61]  P. Pietrini,et al.  Altered brain functional connectivity and impaired short-term memory in Alzheimer's disease. , 2001, Brain : a journal of neurology.

[62]  J R Moeller,et al.  Activate your online subscription , 2000, Neurology.

[63]  Ying Han,et al.  Frequency-dependent changes in the amplitude of low-frequency fluctuations in amnestic mild cognitive impairment: A resting-state fMRI study , 2011, NeuroImage.

[64]  M. Greicius,et al.  Default-mode network activity distinguishes Alzheimer's disease from healthy aging: Evidence from functional MRI , 2004, Proc. Natl. Acad. Sci. USA.

[65]  Zuzana Walker,et al.  The functional anatomy of divided attention in amnestic mild cognitive impairment. , 2005, Brain : a journal of neurology.

[66]  Keith A Hutchison,et al.  Spatial attention and response control in healthy younger and older adults and individuals with Alzheimer's disease: evidence for disproportionate selection impairments in the Simon task. , 2007, Neuropsychology.

[67]  Jin Fan,et al.  Human attentional networks. , 2004, Psychiatrische Praxis.

[68]  J. Miller,et al.  A warning about median reaction time. , 1988, Journal of experimental psychology. Human perception and performance.

[69]  D. Balota,et al.  Memory efficiency and the strategic control of attention at encoding: impairments of value-directed remembering in Alzheimer's disease. , 2009, Neuropsychology.

[70]  J. Muir,et al.  Phasic visual alertness in Alzheimer's disease and ageing , 2002, Neuroreport.

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

[72]  Jin Fan,et al.  Selective impairment of attentional networks of orienting and executive control in schizophrenia , 2005, Schizophrenia Research.

[73]  Vince D. Calhoun,et al.  Alterations in Memory Networks in Mild Cognitive Impairment and Alzheimer's Disease: An Independent Component Analysis , 2006, The Journal of Neuroscience.

[74]  M. Corbetta,et al.  The Reorienting System of the Human Brain: From Environment to Theory of Mind , 2008, Neuron.

[75]  P. Remy,et al.  Executive function deficits in early Alzheimer's disease and their relations with episodic memory. , 2006, Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists.

[76]  N. Herrmann,et al.  Mild Cognitive Impairment: An Operational Definition and Its Conversion Rate to Alzheimer’s Disease , 2005, Dementia and Geriatric Cognitive Disorders.

[77]  R. Turner,et al.  Event-Related fMRI: Characterizing Differential Responses , 1998, NeuroImage.

[78]  J. Hodges,et al.  Attention and executive deficits in Alzheimer's disease. A critical review. , 1999, Brain : a journal of neurology.

[79]  Kathryn Ziegler-Graham,et al.  Forecasting the global burden of Alzheimer’s disease , 2007, Alzheimer's & Dementia.

[80]  J. Haxby,et al.  Sustained Attention in Mild Alzheimer's Disease , 2005, Developmental neuropsychology.

[81]  P. Aisen,et al.  Recent developments in Alzheimer's disease therapeutics , 2009, BMC medicine.

[82]  M. Posner,et al.  The attention system of the human brain. , 1990, Annual review of neuroscience.

[83]  N. Cowan Evolving conceptions of memory storage, selective attention, and their mutual constraints within the human information-processing system. , 1988, Psychological bulletin.

[84]  D. Balota,et al.  Inhibition of return and visuospatial attention in healthy older adults and individuals with dementia of the Alzheimer type. , 1997, Neuropsychology.

[85]  Karl J. Friston,et al.  Analysis of fMRI Time-Series Revisited , 1995, NeuroImage.

[86]  Howard Chertkow,et al.  Selective attention impairments in Alzheimer's disease: evidence for dissociable components. , 2004, Neuropsychology.

[87]  Jin Fan,et al.  The activation of attentional networks , 2005, NeuroImage.

[88]  Ginette Lafleche,et al.  Executive function deficits in mild Alzheimer's disease. , 1995 .

[89]  R. Nebes,et al.  Focused and Divided Attention in Alzheimer's Disease , 1989, Cortex.

[90]  Rema Raman,et al.  Adding Delayed Recall to the Alzheimer Disease Assessment Scale is Useful in Studies of Mild Cognitive Impairment But Not Alzheimer Disease , 2011, Alzheimer disease and associated disorders.