Distinct mechanisms of impairment in cognitive ageing and Alzheimer's disease.

Similar manifestations of functional decline in ageing and Alzheimer's disease obscure differences in the underlying cognitive mechanisms of impairment. We sought to examine the contributions of top-down attentional and bottom-up perceptual factors to visual self-movement processing in ageing and Alzheimer's disease. We administered a novel heading discrimination task requiring subjects to determine direction of simulated self-movement from left or right offset optic flow fields of several sizes (25 degrees, 40 degrees or 60 degrees in diameter) to 18 Alzheimer's disease subjects (mean age = 75.3, 55% female), 21 older adult control subjects (mean age = 72.4, 67% female), and 26 younger control subjects (mean age = 26.5, 63% female). We also administered computerized measures of processing speed and divided and selective attention, and psychophysical measures of visual motion perception to all subjects. Both older groups showed significant difficulty in judging the direction of virtual self-movement [F(2,194) = 40.5, P < 0.001] and optic flow stimulus size had little effect on heading discrimination for any group. Both older groups showed impairments on measures of divided [F(2,62) = 22.2, P < 0.01] and selective [F(2,62) = 63.0, P < 0.001] attention relative to the younger adult control group, while the Alzheimer's disease group showed a selective impairment in outward optic flow perception [F(2,64) = 6.3, P = 0.003] relative to both control groups. Multiple linear regression revealed distinct attentional and perceptual contributions to heading discrimination performance for the two older groups. In older adult control subjects, poorer heading discrimination was attributable to attentional deficits (R(2) adj = 0.41, P = 0.001) whereas, in Alzheimer's disease patients, it was largely attributable to deficits of visual motion perception (R(2) adj = 0.57, P < 0.001). These findings suggest that successive attentional and perceptual deficits play independent roles in the progressive functional impairments of ageing and Alzheimer's disease. We speculate that the attentional deficits that dominate in older adults may promote the development of the perceptual deficits that further constrain performance in Alzheimer's disease.

[1]  H. Braak,et al.  Neuropathological stageing of Alzheimer-related changes , 2004, Acta Neuropathologica.

[2]  R. Parasuraman,et al.  The scaling of spatial attention in visual search and its modification in healthy aging , 2004, Perception & psychophysics.

[3]  R. Petersen,et al.  Clinical, genetic, and neuropathologic characteristics of posterior cortical atrophy , 2004, Neurology.

[4]  C. Duffy,et al.  Behavioral influences on cortical neuronal responses to optic flow. , 2007, Cerebral cortex.

[5]  H. Soininen,et al.  Decline of Frontal Lobe Functions in Subjects with Age-associated Memory Impairment , 1997, Neurology.

[6]  G. Trick,et al.  Visual sensitivity to motion , 1991, Neurology.

[7]  Abass Alavi,et al.  Structural and functional imaging correlates for age-related changes in the brain. , 2007, Seminars in nuclear medicine.

[8]  J. A. Renner,et al.  Progressive posterior cortical dysfunction , 2004, Neurology.

[9]  T. Salthouse The processing-speed theory of adult age differences in cognition. , 1996, Psychological review.

[10]  J. Winn,et al.  Brain , 1878, The Lancet.

[11]  Elisabet Englund,et al.  Regional pattern of degeneration in Alzheimer's disease: neuronal loss and histopathological grading. , 2002, Histopathology.

[12]  M. O’Sullivan,et al.  Incidence of ALS in Italy , 2001, Neurology.

[13]  R. Wurtz,et al.  Planar directional contributions to optic flow responses in MST neurons. , 1997, Journal of neurophysiology.

[14]  S. Black,et al.  Spatial-and object-based attentional deficits in Alzheimer''s disease , 1997 .

[15]  A. Dale,et al.  Thinning of the cerebral cortex in aging. , 2004, Cerebral cortex.

[16]  R. West,et al.  An application of prefrontal cortex function theory to cognitive aging. , 1996, Psychological bulletin.

[17]  P. Greenwood,et al.  The frontal aging hypothesis evaluated , 2000, Journal of the International Neuropsychological Society.

[18]  W Makous,et al.  Visual mechanisms of spatial disorientation in Alzheimer's disease. , 2001, Cerebral cortex.

[19]  M. Lezak Neuropsychological assessment, 3rd ed. , 1995 .

[20]  L. Mucke,et al.  Reducing Endogenous Tau Ameliorates Amyloid ß-Induced Deficits in an Alzheimer's Disease Mouse Model , 2007, Science.

[21]  Charles J Duffy,et al.  A visuospatial variant of mild cognitive impairment , 2003, Neurology.

[22]  M. Folstein,et al.  Clinical diagnosis of Alzheimer's disease , 1984, Neurology.

[23]  R. Wurtz,et al.  An illusory transformation of optic flow fields , 1993, Vision Research.

[24]  Yuka Sasaki,et al.  Greater Disruption Due to Failure of Inhibitory Control on an Ambiguous Distractor , 2006, Science.

[25]  Richard J. A. van Wezel,et al.  An illusory transformation of optic flow fields without local motion interactions , 2004, Vision Research.

[26]  R. Mansfield,et al.  Analysis of visual behavior , 1982 .

[27]  Jeffrey L. Cummings,et al.  Cognitive and behavioral heterogeneity in Alzheimer’s disease: seeking the neurobiological basis , 2000, Neurobiology of Aging.

[28]  Edith V. Sullivan,et al.  Frontal circuitry degradation marks healthy adult aging: Evidence from diffusion tensor imaging , 2005, NeuroImage.

[29]  L. Cauller Layer I of primary sensory neocortex: where top-down converges upon bottom-up , 1995, Behavioural Brain Research.

[30]  L. O. Harvey,et al.  Efficient estimation of sensory thresholds with ML-PEST. , 1997, Spatial vision.

[31]  M. Posner,et al.  Orienting of Attention* , 1980, The Quarterly journal of experimental psychology.

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

[33]  C. Duffy,et al.  Neurophysiological and perceptual correlates of navigational impairment in Alzheimer's disease. , 2006, Brain : a journal of neurology.

[34]  H. Komatsu,et al.  Relation of cortical areas MT and MST to pursuit eye movements. III. Interaction with full-field visual stimulation. , 1988, Journal of neurophysiology.

[35]  Christopher Patrick Taylor,et al.  Aging Reduces Center-Surround Antagonism in Visual Motion Processing , 2005, Neuron.

[36]  Cheryl L. Dahle,et al.  Regional brain changes in aging healthy adults: general trends, individual differences and modifiers. , 2005, Cerebral cortex.

[37]  F. N. Dempster,et al.  The rise and fall of the inhibitory mechanism: Toward a unified theory of cognitive development and aging , 1992 .

[38]  Leslie G. Ungerleider Two cortical visual systems , 1982 .

[39]  J. Morrison,et al.  An Anatomic Substrate for Visual Disconnection in Alzheimer's Disease a , 1991, Annals of the New York Academy of Sciences.

[40]  Tirin Moore,et al.  Changes in Visual Receptive Fields with Microstimulation of Frontal Cortex , 2006, Neuron.

[41]  A. Brun,et al.  Distribution of cerebral degeneration in Alzheimer's disease , 1976, Archiv für Psychiatrie und Nervenkrankheiten.

[42]  T. Albright,et al.  Adaptive Surround Modulation in Cortical Area MT , 2007, Neuron.

[43]  C. Duffy,et al.  Heading representation in MST: sensory interactions and population encoding. , 2003, Journal of neurophysiology.

[44]  G. V. Van Hoesen,et al.  The topographical and neuroanatomical distribution of neurofibrillary tangles and neuritic plaques in the cerebral cortex of patients with Alzheimer's disease. , 1991, Cerebral cortex.

[45]  J. Money,et al.  A standardized road-map test of direction sense , 1965 .

[46]  N Butters,et al.  Directed and divided attention in Alzheimer's disease: impairment in shifting of attention to global and local stimuli. , 1992, Journal of clinical and experimental neuropsychology.

[47]  A. W. Blackwell,et al.  Age differences in perceiving the direction of self-motion from optical flow. , 1989, Journal of gerontology.

[48]  C. Duffy,et al.  Cortical neuronal responses to optic flow are shaped by visual strategies for steering. , 2008, Cerebral cortex.

[49]  D. Gitelman,et al.  Dynamic allocation of attention in aging and Alzheimer disease: uncoupling of the eye and mind. , 2001, Archives of neurology.

[50]  A. Leventhal,et al.  GABA and Its Agonists Improved Visual Cortical Function in Senescent Monkeys , 2003, Science.

[51]  M. Mamelak Alzheimer’ s disease, oxidative stress and gammahydroxybutyrate , 2007, Neurobiology of Aging.

[52]  M. Mesulam,et al.  From sensation to cognition. , 1998, Brain : a journal of neurology.

[53]  C. Duffy,et al.  Neurophysiologic analyses of low- and high-level visual processing in Alzheimer disease , 2007, Neurology.