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Insights into the ageing mind: a view from cognitive neuroscience

Key Points

  • A number of physical and mental changes accompany the developmental process of ageing; some of the most prominent of these involve changes in memory function. This article reviews the main behavioural findings in cognitive ageing research, and the structural and functional brain basis of the memory changes that occur with age.

  • Cross-sectional behavioural research has found robust declines across the adult lifespan in the ability to form new episodic memories, to process information quickly and to invoke executive processes, although longitudinal studies indicate that these declines might occur primarily after the age of 60. Semantic memory and short-term memory show remarkable preservation across most of the adult lifespan, with declines occurring only very late in life. By contrast, autobiographical memory, emotional memory and implicit memory are relatively unaffected by ageing.

  • Structural changes in both grey and white matter map onto these behavioural changes in memory. The largest volumetric declines occur in the prefrontal cortex, which subserves strategic episodic encoding and executive processes. The loss of anterior white matter integrity and of dopamine receptors in the striatum and prefrontal cortex accompany these volumetric declines, further providing mechanisms for the disruption of circuits that underlie memory function.

  • Hippocampal volume declines are less apparent during normal ageing, although declines in functional activations of the hippocampus and surrounding cortex have been observed in healthy older adults. By contrast, pathological processes, such as those that accompany Alzheimer's disease, severely affect hippocampal regions. In particular, entorhinal cortex, which serves as an important relay between the prefrontal cortex and the hippocampus, is disproportionately affected by pathology.

  • The differential pattern of age-related changes in the prefrontal cortex and the hippocampus indicates a two-component model of cognitive ageing, with normal ageing primarily affecting prefrontal areas, and pathological ageing affecting medial temporal regions.

  • There is, however, wide variability among individuals in the extent, rate and pattern of age-related changes that are exhibited at both neural and behavioural levels. Some older adults have relatively intact memory function and also show patterns of functional activity in the prefrontal cortex that are often interpreted as being compensatory. Through investigation of differences among those older adults that are most resistant to and affected by ageing, researchers hope to determine how normal ageing affects cognition and how these effects might be mitigated.

Abstract

As we grow older, we may grow wiser, but we can also experience memory loss and cognitive slowing that can interfere with our daily routines. The cognitive neuroscience of human ageing, which relies largely on neuroimaging techniques, relates these cognitive changes to their neural substrates, including structural and functional changes in the prefrontal cortex, medial temporal lobe regions and white matter tracts. Much remains unknown about how normal ageing affects the neural basis of cognition, but recent research on individual differences in the trajectory of ageing effects is helping to distinguish normal from pathological origins of age-related cognitive changes.

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Figure 1: Cross-sectional and longitudinal estimates of age-related change in cognition.
Figure 2: Cross-sectional estimates of age-related volumetric change in lateral prefrontal cortex, visual cortex and hippocampus measured with magnetic resonance imaging.
Figure 3: Diffusion tensor images of anisotropy of white matter in young and normal elderly subjects.
Figure 4: Functional magnetic resonance imaging activations for subsequently remembered words.
Figure 5: Neural activations in prefrontal cortex during a memory encoding task.

References

  1. Salthouse, T. A. & Ferrer-Caja, E. What needs to be explained to account for age-related effects on multiple cognitive variables? Psychol. Aging 18, 91–110 (2003).

    Article  PubMed  Google Scholar 

  2. Craik, F. I. M. Memory changes in normal aging. Curr. Dir. Psychol. Sci. 3, 155–158 (1994).

    Article  Google Scholar 

  3. Park, D. C. et al. Mediators of long-term memory performance across the life span. Psychol. Aging 11, 621–637 (1996).

    Article  CAS  PubMed  Google Scholar 

  4. Park, D. C. et al. Models of visuospatial and verbal memory across the adult life span. Psychol. Aging 17, 299–320 (2002).

    Article  PubMed  Google Scholar 

  5. Schaie, K. W. Intellectual Development in Adulthood: The Seattle Longitudinal Study (Cambridge Univ. Press, Cambridge, 1996). This seminal longitudinal study of cognitive ageing followed 7 age cohorts across 35 years.

    Google Scholar 

  6. Hultsch, D. F., Hertzog, C., Dixon, R. A. & Small, B. J. Memory Change in the Aged (Cambridge Univ. Press, New York, 1998).

    Google Scholar 

  7. Zelinski, E. M. & Burnight, K. P. Sixteen-year longitudinal and time lag changes in memory and cognition in older adults. Psychol. Aging 12, 503–513 (1997).

    Article  CAS  PubMed  Google Scholar 

  8. Small, B. J., Fratiglioni, L., von Strauss, E. & Bäckman, L. Terminal decline and cognitive performance in very old age: does cause of death matter? Psychol. Aging 18, 193–202 (2003).

    Article  PubMed  Google Scholar 

  9. Wilson, R. S., Beckett, L. A., Bienias, J. L., Evans, D. A. & Bennett, D. A. Terminal decline in cognitive function. Neurology 60, 1782–1787 (2003).

    Article  CAS  PubMed  Google Scholar 

  10. Gregoire, J. & Van der Linden, M. Effects of age on forward and backward digit spans. Aging Neuropsychol. Cogn. 4, 140–149 (1997).

    Article  Google Scholar 

  11. Baltes, P. B., Staudinger, U. M., Maercker, A. & Smith, J. People nominated as wise: a comparative study of wisdom-related knowledge. Psychol. Aging 10, 155–166 (1995).

    Article  CAS  PubMed  Google Scholar 

  12. Shimamura, A. P. et al. Memory and cognitive abilities in university professors: evidence for successful aging. Psychol. Sci. 6, 271–277 (1995).

    Article  Google Scholar 

  13. Hedden, T., Lautenschlager, G. & Park, D. C. Contributions of processing ability and knowledge to verbal memory tasks across the adult life span. Q. J. Exp. Psychol. (in the press).

  14. Dixon, R. A., de Frias, C. M. & Baeckman, L. Characteristics of self-reported memory compensation in older adults. J. Clin. Exp. Neuropsychol. 23, 650–661 (2001).

    Article  CAS  PubMed  Google Scholar 

  15. Fromholt, P. et al. Life-narrative and word-cued autobiographical memories in centenarians: comparisons with 80-year-old control, depressed, and dementia groups. Memory 11, 81–88 (2003).

    Article  PubMed  Google Scholar 

  16. Happe, F. G., Winner, E. & Brownell, H. The getting of wisdom: theory of mind in old age. Dev. Psychol. 34, 358–362 (1998).

    Article  CAS  PubMed  Google Scholar 

  17. Carstensen, L. L., Fung, H. H. & Charles, S. T. Socioemotional selectivity theory and the regulation of emotion in the second half of life. Motivation Emotion 27, 103–123 (2003).

    Article  Google Scholar 

  18. La Voie, D. & Light, L. L. Adult age differences in repetition priming: a meta-analysis. Psychol. Aging 9, 539–553 (1994).

    Article  CAS  PubMed  Google Scholar 

  19. Jacoby, L. L. Ironic effects of repetition: measuring age-related differences in memory. J. Exp. Psychol. Learn. Mem. Cogn. 25, 3–22 (1999).

    Article  CAS  PubMed  Google Scholar 

  20. Spencer, W. D. & Raz, N. Differential effects of aging on memory for content and context: a meta-analysis. Psychol. Aging 10, 527–539 (1995).

    Article  CAS  PubMed  Google Scholar 

  21. Haug, H. & Eggers, R. Morphometry of the human cortex cerebri and corpus striatum during aging. Neurobiol. Aging 12, 336–338 (1991).

    Article  CAS  PubMed  Google Scholar 

  22. Resnick, S. M., Pham, D. L., Kraut, M. A., Zonderman, A. B. & Davatzikos, C. Longitudinal magnetic resonance imaging studies of older adults: a shrinking brain. J. Neurosci. 23, 3295–3301 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Terry, R. D. Cell death or synaptic loss in Alzheimer disease. J. Neuropathol. Exp. Neurol. 59, 1118–1119 (2000).

    Article  CAS  PubMed  Google Scholar 

  24. Terry, R. D. & Katzman, R. Life span and synapses: will there be a primary senile dementia? Neurobiol. Aging 22, 347–348 (2001).

    Article  CAS  PubMed  Google Scholar 

  25. Raz, N. et al. Aging, sexual dimorphism, and hemispheric asymmetry of the cerebral cortex: replicability of regional differences in volume. Neurobiol. Aging (in the press).

  26. Raz, N. et al. Differential aging of the human striatum: longitudinal evidence. Am. J. Neuroradiol. (in the press).

  27. West, R. L. An application of prefrontal cortex function theory to cognitive aging. Psychol. Bull. 120, 272–292 (1996). An important review of the relationships between PFC and cognitive ageing effects.

    Article  CAS  PubMed  Google Scholar 

  28. Gabrieli, J. D. Memory systems analyses of mnemonic disorders in aging and age-related diseases. Proc. Natl Acad. Sci. USA 93, 13534–13540 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Volkow, N. D. et al. Measuring age-related changes in dopamine D2 receptors with 11C-raclopride and 18F-N-methylspiroperidol. Psychiatry Res. 67, 11–16 (1996).

    Article  CAS  PubMed  Google Scholar 

  30. Head, D. et al. Differential vulnerability of anterior white matter in nondemented aging with minimal acceleration in dementia of the Alzheimer type: evidence from diffusion tensor imaging. Cereb. Cortex (in the press). This paper offers a comprehensive DTI study of white matter changes in normal and demented ageing.

  31. Li, S. C. & Sikstrom, S. Integrative neurocomputational perspectives on cognitive aging, neuromodulation, and representation. Neurosci. Biobehav. Rev. 26, 795–808 (2002).

    Article  PubMed  Google Scholar 

  32. Braver, T. S. & Barch, D. M. A theory of cognitive control, aging cognition, and neuromodulation. Neurosci. Biobehav. Rev. 26, 809–817 (2002).

    Article  PubMed  Google Scholar 

  33. Braak, H. et al. Pattern of brain destruction in Parkinson's and Alzheimer's diseases. J. Neural Transm. 103, 455–490 (1996).

    Article  CAS  PubMed  Google Scholar 

  34. Dickerson, B. C. et al. MRI-derived entorhinal and hippocampal atrophy in incipient and very mild Alzheimer's disease. Neurobiol. Aging 22, 747–754 (2001).

    Article  CAS  PubMed  Google Scholar 

  35. Killiany, R. J. et al. Use of structural magnetic resonance imaging to predict who will get Alzheimer's disease. Ann. Neurol. 47, 430–439 (2000). Shows that volume of entorhinal cortex is related to subsequent progression to dementia.

    Article  CAS  PubMed  Google Scholar 

  36. Sliwinski, M., Lipton, R. B., Buschke, H. & Stewart, W. The effects of preclinical dementia on estimates of normal cognitive functioning in aging. J. Gerontol. B Psychol. Sci. Soc. Sci. 51, 217–225 (1996).

    Article  Google Scholar 

  37. Moscovitch, M. & Winocur, G. Frontal lobes, memory, and aging. Ann. NY Acad. Sci. 769, 119–150 (1995).

    Article  CAS  PubMed  Google Scholar 

  38. Raz, N., Gunning-Dixon, F. M., Head, D., Dupuis, J. H. & Acker, J. D. Neuroanatomical correlates of cognitive aging: evidence from structural magnetic resonance imaging. Neuropsychology 12, 95–114 (1998). This study demonstrated relationships between PFC volume and executive function, and between hippocampal volume and explicit memory, in later life.

    Article  CAS  PubMed  Google Scholar 

  39. Tisserand, D. J. et al. Regional frontal cortical volumes decrease differentially in aging: an MRI study to compare volumetric approaches and voxel-based morphometry. Neuroimage 17, 657–669 (2002).

    Article  PubMed  Google Scholar 

  40. Salat, D. H., Kaye, J. A. & Janowsky, J. S. Selective preservation and degeneration within the prefrontal cortex in aging and Alzheimer disease. Arch. Neurol. 58, 1403–1408 (2001).

    Article  CAS  PubMed  Google Scholar 

  41. Thompson, P. M. et al. Dynamics of gray matter loss in Alzheimer's disease. J. Neurosci. 23, 994–1005 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Bourgeois, J. P., Goldman-Rakic, P. S. & Rakic, P. Synaptogenesis in the prefrontal cortex of rhesus monkeys. Cereb. Cortex 4, 78–96 (1994).

    Article  CAS  PubMed  Google Scholar 

  43. Liu, X., Erikson, C. & Brun, A. Cortical synaptic changes and gliosis in normal aging, Alzheimer's disease and frontal lobe degeneration. Dementia 7, 128–134 (1996).

    CAS  PubMed  Google Scholar 

  44. Gunning-Dixon, F. M., Head, D., McQuain, J., Acker, J. D. & Raz, N. Differential aging of the human striatum: a prospective MR imaging study. Am. J. Neuroradiol. 19, 1501–1507 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Goldman-Rakic, P. S. & Brown, R. M. Regional changes of monoamines in cerebral cortex and subcortical structures of aging rhesus monkeys. Neuroscience 6, 177–187 (1981).

    Article  CAS  PubMed  Google Scholar 

  46. Volkow, N. D. et al. Parallel loss of presynaptic and postsynaptic dopamine markers in normal aging. Ann. Neurol. 44, 143–147 (1998).

    Article  CAS  PubMed  Google Scholar 

  47. Volkow, N. D. et al. Association between age-related decline in brain dopamine activity and impairment in frontal and cingulate metabolism. Am. J. Psychiatry 157, 75–80 (2000). The first study to show a correlation of frontal and cingulate function with age-related declines in dopamine receptors.

    Article  CAS  PubMed  Google Scholar 

  48. Wang, G. J. et al. Evaluation of age-related changes in serotonin 5-HT2 and dopamine D2 receptor availability in healthy human subjects. Life Sci. 56, PL249–253 (1995).

    CAS  PubMed  Google Scholar 

  49. Sheline, Y. I., Mintun, M. A., Moerlein, S. M. & Snyder, A. Z. Greater loss of 5-HT2A receptors in midlife than in late life. Am. J. Psychiatry 159, 430–435 (2002).

    Article  PubMed  Google Scholar 

  50. Schretlen, D. et al. Elucidating the contributions of processing speed, executive ability, and frontal lobe volume to normal age-related differences in fluid intelligence. J. Int. Neuropsychol. Soc. 6, 52–61 (2000).

    Article  CAS  PubMed  Google Scholar 

  51. Arnsten, A. F. & Goldman-Rakic, P. S. α2-Adrenergic mechanisms in prefrontal cortex associated with cognitive decline in aged non-human primates. Science 230, 1273–1276 (1985).

    Article  CAS  PubMed  Google Scholar 

  52. Arnsten, A. F., Cai, J. X., Steere, J. C. & Goldman-Rakic, P. S. Dopamine D2 receptor mechanisms contribute to age-related cognitive decline: the effects of quinpirole on memory and motor performance in monkeys. J. Neurosci. 15, 3429–3439 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Volkow, N. D. et al. Association between decline in brain dopamine activity with age and cognitive and motor impairment in healthy individuals. Am. J. Psychiatry 155, 344–349 (1998).

    Article  CAS  PubMed  Google Scholar 

  54. Bäckman, L. et al. Age-related cognitive deficits mediated by changes in the striatal dopamine system. Am. J. Psychiatry 157, 635–637 (2000). An important study demonstrating that age-related declines in dopamine receptors account for declines in performance on speed of processing and episodic memory tasks.

    Article  PubMed  Google Scholar 

  55. Bunge, S. A., Ochsner, K. N., Desmond, J. E., Glover, G. H. & Gabrieli, J. D. Prefrontal regions involved in keeping information in and out of mind. Brain 124, 2074–2086 (2001).

    Article  CAS  PubMed  Google Scholar 

  56. Rypma, B., Berger, J. S. & D'Esposito, M. The influence of working-memory demand and subject performance on prefrontal cortical activity. J. Cogn. Neurosci. 14, 721–731 (2002).

    Article  PubMed  Google Scholar 

  57. D'Esposito, M., Postle, B. R., Jonides, J. & Smith, E. E. The neural substrate and temporal dynamics of interference effects in working memory as revealed by event-related functional MRI. Proc. Natl Acad. Sci. USA 96, 7514–7519 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Hazeltine, E., Bunge, S. A., Scanlon, M. D. & Gabrieli, J. D. Material-dependent and material-independent selection processes in the frontal and parietal lobes: an event-related fMRI investigation of response competition. Neuropsychologia 41, 1208–1217 (2003).

    Article  PubMed  Google Scholar 

  59. Bunge, S. A., Kahn, I., Wallis, J. D., Miller, E. K. & Wagner, A. D. Neural circuits subserving the retrieval and maintenance of abstract rules. J. Neurophysiol. (in the press).

  60. Dreher, J. C. & Grafman, J. Dissociating the roles of the rostral anterior cingulate and the lateral prefrontal cortices in performing two tasks simultaneously or successively. Cereb. Cortex 13, 329–339 (2003).

    Article  PubMed  Google Scholar 

  61. Konishi, S., Wheeler, M. E., Donaldson, D. I. & Buckner, R. L. Neural correlates of episodic retrieval success. Neuroimage 12, 276–286 (2000).

    Article  CAS  PubMed  Google Scholar 

  62. Wagner, A. D., Maril, A., Bjork, R. A. & Schacter, D. L. Prefrontal contributions to executive control: fMRI evidence for functional distinctions within lateral prefrontal cortex. Neuroimage 14, 1337–1347 (2001).

    Article  CAS  PubMed  Google Scholar 

  63. Rypma, B. & D'Esposito, M. Isolating the neural mechanisms of age-related changes in human working memory. Nature Neurosci. 3, 509–515 (2000). This imaging study provided evidence that age-related declines in working memory retrieval are mediated by dorsolateral PFC, and that the relationship between speed of retrieval and PFC activation reverses with age.

    Article  CAS  PubMed  Google Scholar 

  64. Stebbins, G. T. et al. Aging effects on memory encoding in the frontal lobes. Psychol. Aging 17, 44–55 (2002).

    Article  PubMed  Google Scholar 

  65. Logan, J. M., Sanders, A. L., Snyder, A. Z., Morris, J. C. & Buckner, R. L. Under-recruitment and nonselective recruitment: dissociable neural mechanisms associated with aging. Neuron 33, 827–840 (2002).

    Article  CAS  PubMed  Google Scholar 

  66. Cabeza, R. Hemispheric asymmetry reduction in older adults: the HAROLD model. Psychol. Aging 17, 85–100 (2002).

    Article  PubMed  Google Scholar 

  67. Grady, C. L. et al. Age-related changes in regional cerebral blood flow during working memory for faces. Neuroimage 8, 409–425 (1998).

    Article  CAS  PubMed  Google Scholar 

  68. Rypma, B., Prabhakaran, V., Desmond, J. E. & Gabrieli, J. D. Age differences in prefrontal cortical activity in working memory. Psychol. Aging 16, 371–384 (2001).

    Article  CAS  PubMed  Google Scholar 

  69. Jonides, J. et al. Age differences in behavior and PET activation reveal differences in interference resolution in verbal working memory. J. Cogn. Neurosci. 12, 188–196 (2000).

    Article  CAS  PubMed  Google Scholar 

  70. DiGirolamo, G. J. et al. General and task-specific frontal lobe recruitment in older adults during executive processes: a fMRI investigation of task-switching. Neuroreport 12, 2065–2071 (2001).

    Article  CAS  PubMed  Google Scholar 

  71. Chen, Z. G., Li, T. Q. & Hindmarsh, T. Diffusion tensor trace mapping in normal adult brain using single-shot EPI technique. A methodological study of the aging brain. Acta Radiol. 42, 447–458 (2001).

    CAS  PubMed  Google Scholar 

  72. Guttmann, C. R. et al. White matter changes with normal aging. Neurology 50, 972–978 (1998).

    Article  CAS  PubMed  Google Scholar 

  73. Bartzokis, G. et al. White matter structural integrity in healthy aging adults and patients with Alzheimer disease: a magnetic resonance imaging study. Arch. Neurol. 60, 393–398 (2003).

    Article  PubMed  Google Scholar 

  74. O'Sullivan, M. et al. Evidence for cortical 'disconnection' as a mechanism of age-related cognitive decline. Neurology 57, 632–638 (2001).

    Article  CAS  PubMed  Google Scholar 

  75. Gunning-Dixon, F. M. & Raz, N. The cognitive correlates of white matter abnormalities in normal aging: a quantitative review. Neuropsychology 14, 224–232 (2000).

    Article  CAS  PubMed  Google Scholar 

  76. Erickson, C. A. & Barnes, C. A. The neurobiology of memory changes in normal aging. Exp. Gerontol. 38, 61–69 (2003).

    Article  CAS  PubMed  Google Scholar 

  77. Rapp, P. R., Deroche, P. S., Mao, Y. & Burwell, R. D. Neuron number in the parahippocampal region is preserved in aged rats with spatial learning deficits. Cereb. Cortex 12, 1171–1179 (2002).

    Article  PubMed  Google Scholar 

  78. Rasmussen, T., Schliemann, T., Sorensen, J. C., Zimmer, J. & West, M. J. Memory impaired aged rats: no loss of principal hippocampal and subicular neurons. Neurobiol. Aging 17, 143–147 (1996).

    Article  CAS  PubMed  Google Scholar 

  79. West, M. J. Regionally specific loss of neurons in the aging human hippocampus. Neurobiol. Aging 14, 287–293 (1993).

    Article  CAS  PubMed  Google Scholar 

  80. Flood, D. G., Buell, S. J., Horwitz, G. J. & Coleman, P. D. Dendritic extent in human dentate gyrus granule cells in normal aging and senile dementia. Brain Res. 402, 205–216 (1987).

    Article  CAS  PubMed  Google Scholar 

  81. Kempermann, G., Gast, D., Kronenberg, G., Yamaguchi, M. & Gage, F. H. Early determination and long-term persistence of adult-generated new neurons in the hippocampus of mice. Development 130, 391–399 (2003).

    Article  CAS  PubMed  Google Scholar 

  82. Raz, N., Rodrigue, K. M., Head, D., Kennedy, K. M. & Acker, J. D. Differential aging of the medial temporal lobe: a study of a five-year change. Neurology (in the press).

  83. Jack, C. R. Jr et al. Rate of medial temporal lobe atrophy in typical aging and Alzheimer's disease. Neurology 51, 993–999 (1998).

    Article  PubMed  Google Scholar 

  84. Rosen, A. C. et al. Differential associations between entorhinal and hippocampal volumes and memory performance in older adults. Behav. Neurosci. (in the press).

  85. Small, S. A., Tsai, W. Y., DeLaPaz, R., Mayeux, R. & Stern, Y. Imaging hippocampal function across the human life span: is memory decline normal or not? Ann. Neurol. 51, 290–295 (2002). A provocative paper that used structural imaging to show differential influences of normal ageing and pathology on hippocampal subregions.

    Article  PubMed  Google Scholar 

  86. Zeineh, M. M., Engel, S. A., Thompson, P. M. & Bookheimer, S. Y. Dynamics of the hippocampus during encoding and retrieval of face-name pairs. Science 299, 577–580 (2003).

    Article  CAS  PubMed  Google Scholar 

  87. Daselaar, S. M., Veltman, D. J., Rombouts, S. A., Raaijmakers, J. G. & Jonker, C. Neuroanatomical correlates of episodic encoding and retrieval in young and elderly subjects. Brain 126, 43–56 (2003).

    Article  CAS  PubMed  Google Scholar 

  88. Mitchell, K. J., Johnson, M. K., Raye, C. L. & D'Esposito, M. fMRI evidence of age-related hippocampal dysfunction in feature binding in working memory. Brain Res. Cogn. Brain Res. 10, 197–206 (2000). This study demonstrates a contribution of the hippocampus to age-related deficits in binding multiple features of a memory representation.

    Article  CAS  PubMed  Google Scholar 

  89. Morcom, A. M., Good, C. D., Frackowiak, R. S. & Rugg, M. D. Age effects on the neural correlates of successful memory encoding. Brain 126, 213–229 (2003).

    Article  PubMed  Google Scholar 

  90. Park, D. C. et al. Working memory for complex scenes: age differences in frontal and hippocampal activations. J. Cogn. Neurosci. (in the press).

  91. Sperling, R. A. et al. fMRI studies of associative encoding in young and elderly controls and mild Alzheimer's disease. J. Neurol. Neurosurg. Psychiatry 74, 44–50 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Cabeza, R., Anderson, N. D., Locantore, J. K. & McIntosh, A. R. Aging gracefully: compensatory brain activity in high-performing older adults. Neuroimage 17, 1394–1402 (2002). A well-designed study showing that bilateral functional activity exhibited by older adults is related to higher memory performance.

    Article  PubMed  Google Scholar 

  93. Rosen, A. C. et al. Variable effects of aging on frontal lobe contributions to memory. Neuroreport 13, 2425–2428 (2002).

    Article  PubMed  Google Scholar 

  94. Iidaka, T. et al. Age-related differences in the medial temporal lobe responses to emotional faces as revealed by fMRI. Hippocampus 12, 352–362 (2002).

    Article  PubMed  Google Scholar 

  95. Mather, M. et al. Amygdala responses to emotionally valenced stimuli in older and younger adults. Psychol. Sci. (in the press).

  96. Good, C. D. et al. A voxel-based morphometric study of ageing in 465 normal adult human brains. Neuroimage 14, 21–36 (2001).

    Article  CAS  PubMed  Google Scholar 

  97. Soininen, H. S. et al. Volumetric MRI analysis of the amygdala and the hippocampus in subjects with age-associated memory impairment: correlation to visual and verbal memory. Neurology 44, 1660–1668 (1994).

    Article  CAS  PubMed  Google Scholar 

  98. Gunning-Dixon, F. M. et al. Age-related differences in brain activation during emotional face processing. Neurobiol. Aging 24, 285–295 (2003).

    Article  PubMed  Google Scholar 

  99. Ylikoski, R. et al. Heterogeneity of cognitive profiles in aging: successful aging, normal aging, and individuals at risk for cognitive decline. Eur. J. Neurol. 6, 645–652 (1999).

    Article  CAS  PubMed  Google Scholar 

  100. Small, S. A. Age-related memory decline: current concepts and future directions. Arch. Neurol. 58, 360–364 (2001).

    Article  CAS  PubMed  Google Scholar 

  101. Hultsch, D. F., MacDonald, S. W. & Dixon, R. A. Variability in reaction time performance of younger and older adults. J. Gerontol. B Psychol. Sci. Soc. Sci. 57, P101–115 (2002).

    Article  PubMed  Google Scholar 

  102. Shammi, P., Bosman, E. & Stuss, D. T. Aging and variability in performance. Aging Neuropsychol. Cogn. 5, 1–13 (1998).

    Article  Google Scholar 

  103. Rapp, P. R. & Amaral, D. G. Individual differences in the cognitive and neurobiological consequences of normal aging. Trends Neurosci. 15, 340–345 (1992).

    Article  CAS  PubMed  Google Scholar 

  104. Hedden, T. & Park, D. C. Contributions of source and inhibitory mechanisms to age-related retroactive interference in verbal working memory. J. Exp. Psychol. Gen. 132, 93–112 (2003).

    Article  PubMed  Google Scholar 

  105. Lindenberger, U. & Baltes, P. B. Sensory functioning and intelligence in old age: a strong connection. Psychol. Aging 9, 339–355 (1994).

    Article  CAS  PubMed  Google Scholar 

  106. Wilson, R. S. et al. Individual differences in rates of change in cognitive abilities of older persons. Psychol. Aging 17, 179–193 (2002).

    Article  PubMed  Google Scholar 

  107. Glisky, E. L., Rubin, S. R. & Davidson, P. S. R. Source memory in older adults: an encoding or retrieval problem? J. Exp. Psychol. Learn. Mem. Cogn. 27, 1131–1146 (2001). An important investigation of individual variability in ageing, this study found that neuropsychological measures of frontal, but not hippocampal, function predict individual differences in source memory preformance.

    Article  CAS  PubMed  Google Scholar 

  108. Davidson, P. S. R. & Glisky, E. L. Neuropsychological correlates of recollection and familiarity in normal aging. Cogn. Affect. Behav. Neurosci. 2, 174–186 (2002).

    Article  PubMed  Google Scholar 

  109. D'Esposito, M., Deouell, L. & Gazzaley, A. The impact of alterations of neurovascular coupling on BOLD fMRI signal: implications for studies of aging and disease. Nature Rev. Neurosci. 4, 863–872 (2003).

    Article  CAS  Google Scholar 

  110. Reuter-Lorenz, P. A. et al. Age differences in the frontal lateralization of verbal and spatial working memory revealed by PET. J. Cogn. Neurosci. 12, 174–187 (2000). This study first suggested that bilateral activity in older adults might be due to compensatory mechanisms.

    Article  CAS  PubMed  Google Scholar 

  111. Reuter-Lorenz, P. A. New visions of the aging mind and brain. Trends Cogn. Sci. 6, 394–400 (2002).

    Article  PubMed  Google Scholar 

  112. Smith, E. E. et al. The neural basis of task-switching in working memory: effects of performance and aging. Proc. Natl Acad. Sci. USA 98, 2095–2100 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Meyer, D. E., Glass, J. M., Mueller, S. T., Seymour, T. L. & Kieras, D. E. Executive-process interactive control: a unified computational theory for answering 20 questions (and more) about cognitive ageing. Eur. J. Cogn. Psychol. 13, 123–164 (2001).

    Article  Google Scholar 

  114. Hasher, L. & Zacks, R. T. in The Psychology of Learning and Motivation: Advances in Research and Theory (ed. Bower, G. H.) 193–225 (Academic, San Diego, 1988).

    Google Scholar 

  115. Riemenschneider, M. et al. A polymorphism of the brain-derived neurotrophic factor (BDNF) is associated with Alzheimer's disease in patients lacking the Apolipoprotein E ε4 allele. Mol. Psychiatry 7, 782–785 (2002).

    Article  CAS  PubMed  Google Scholar 

  116. Hariri, A. R. et al. Brain-derived neurotrophic factor val66met polymorphism affects human memory-related hippocampal activity and predicts memory performance. J. Neurosci. 23, 6690–6694 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Herndon, L. A. et al. Stochastic and genetic factors influence tissue-specific decline in ageing C. elegans. Nature 419, 808–814 (2002).

    Article  CAS  PubMed  Google Scholar 

  118. Small, S. A., Stern, Y., Tang, M. & Mayeux, R. Selective decline in memory function among healthy elderly. Neurology 52, 1392–1396 (1999).

    Article  CAS  PubMed  Google Scholar 

  119. Hofer, S. M. & Sliwinski, M. J. Understanding ageing. An evaluation of research designs for assessing the interdependence of ageing-related changes. Gerontology 47, 341–352 (2001).

    Article  CAS  PubMed  Google Scholar 

  120. Salthouse, T. A. & Nesselroade, J. R. An examination of the Hofer and Sliwinski evaluation. Gerontology 48, 18–21 (2002).

    Article  PubMed  Google Scholar 

  121. Basser, P. J., Mattiello, J. & LeBihan, D. MR diffusion tensor spectroscopy and imaging. Biophys. J. 66, 259–267 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Moseley, M., Bammer, R. & Illes, J. Diffusion-tensor imaging of cognitive performance. Brain Cogn. 50, 396–413 (2002).

    Article  PubMed  Google Scholar 

  123. Petersen, R. C. et al. Mild cognitive impairment: clinical characterization and outcome. Arch. Neurol. 56, 303–338 (1999).

    Article  CAS  PubMed  Google Scholar 

  124. Rusinek, H. et al. Regional brain atrophy rate predicts future cognitive decline: 6-year longitudinal MR imaging study of normal aging. Radiology 229, 691–696 (2003).

    Article  PubMed  Google Scholar 

  125. Small, S. A., Nava, A. S., Perera, G. M., Delapaz, R. & Stern, Y. Evaluating the function of hippocampal subregions with high-resolution MRI in Alzheimer's disease and aging. Microsc. Res. Tech. 51, 101–108 (2000).

    Article  CAS  PubMed  Google Scholar 

  126. Guillozet, A. L., Weintraub, S., Mash, D. C. & Mesulam, M. M. Neurofibrillary tangles, amyloid, and memory in aging and mild cognitive impairment. Arch. Neurol. 60, 729–736 (2003).

    Article  PubMed  Google Scholar 

  127. Albert, S. M. et al. Functional significance of mild cognitive impairment in elderly patients without a dementia diagnosis. Am. J. Geriatr. Psychiatry 7, 213–220 (1999).

    Article  CAS  PubMed  Google Scholar 

  128. Albert, M. S. et al. Predictors of cognitive change in older persons: MacArthur studies of successful aging. Psychol. Aging 10, 578–589 (1995).

    Article  CAS  PubMed  Google Scholar 

  129. Hultsch, D. F., Hertzog, C., Small, B. J. & Dixon, R. A. Use it or lose it: engaged lifestyle as a buffer of cognitive decline in aging? Psychol. Aging 14, 245–263 (1999).

    Article  CAS  PubMed  Google Scholar 

  130. Wilson, R. S. et al. Participation in cognitively stimulating activities and risk of incident Alzheimer disease. J. Am. Med. Assoc. 287, 742–748 (2002).

    Article  Google Scholar 

  131. Kempermann, G., Gast, D. & Gage, F. H. Neuroplasticity in old age: sustained fivefold induction of hippocampal neurogenesis by long-term environmental enrichment. Ann. Neurol. 52, 135–143 (2002).

    Article  PubMed  Google Scholar 

  132. Kramer, A. F. et al. Ageing, fitness and neurocognitive function. Nature 400, 418–419 (1999).

    Article  CAS  PubMed  Google Scholar 

  133. Colcombe, S. J. et al. Aerobic fitness reduces brain tissue loss in aging humans. J. Gerontol. A Biol. Sci. Med. Sci. 58, 176–180 (2003). Demonstrates the neuroprotective effects of aerobic exercise for older adults.

    Article  PubMed  Google Scholar 

  134. Tabbarah, M., Crimmins, E. M. & Seeman, T. E. The relationship between cognitive and physical performance: MacArthur studies of successful aging. J. Gerontol. A Biol. Sci. Med. Sci. 57, M228–235 (2002).

    Article  PubMed  Google Scholar 

  135. Wilson, R. S. et al. Proneness to psychological distress is associated with risk of Alzheimer's disease. Neurology 61, 1479–1485 (2003).

    Article  CAS  PubMed  Google Scholar 

  136. Sapolsky, R. M. Stress, The Aging Brain, and The Mechanisms of Neuron Death (MIT Press, Cambridge, Massachusetts, 1992).

    Google Scholar 

  137. de Leon, M. J. et al. Cortisol reduces hippocampal glucose metabolism in normal elderly, but not in Alzheimer's disease. J. Clin. Endocrinol. Metab. 82, 3251–3259 (1997).

    CAS  PubMed  Google Scholar 

  138. Morris, M. C. et al. Consumption of fish and n-3 fatty acids and risk of incident Alzheimer disease. Arch. Neurol. 60, 940–946 (2003).

    Article  PubMed  Google Scholar 

  139. Solfrizzi, V. et al. High monounsaturated fatty acids intake protects against age-related cognitive decline. Neurology 52, 1563–1569 (1999).

    Article  CAS  PubMed  Google Scholar 

  140. Morris, M. C., Evans, D. A., Bienias, J. L., Tangney, C. C. & Wilson, R. S. Vitamin E and cognitive decline in older persons. Arch. Neurol. 59, 1125–1132 (2002).

    Article  PubMed  Google Scholar 

  141. Galli, R. L., Shukitt-Hale, B., Youdim, K. A. & Joseph, J. A. Fruit polyphenolics and brain aging: nutritional interventions targeting age–related neuronal and behavioral deficits. Ann. NY Acad. Sci. 959, 128–132 (2002).

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

T.H. is supported by an NRSA fellowship from the National Institutes of Health. This review was supported by grants from the National Institute on Ageing to J.D.E.G. The authors thank A. Wagner, A. Rosen, D. Bergerbest and K. Goosens for comments on earlier drafts.

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Correspondence to Trey Hedden.

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DATABASES

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Alzheimer disease

Parkinson disease

FURTHER INFORMATION

Encyclopedia of Life Sciences

ageing and the brain

Gabrieli Cognitive Neuroscience Laboratory

Glossary

EXECUTIVE PROCESSES

General purpose cognitive mechanisms for goal-oriented organization and manipulation of information stored in working memory, and for switching among several tasks and sources of information.

FRONTOSTRIATAL SYSTEM

The frontal lobes and the basal ganglia (striatum and other related structures) are powerfully interconnected by several anatomically segregated loops from the frontal cortex to the striatum through the thalamus and back to the frontal cortex. So, many motor, cognitive and emotional actions are mediated by interactions among the components of this frontostriatal system.

WISCONSIN CARD SORTING TASK

A test that is used to measure behavioural flexibility in which subjects receive cards with different symbols and are asked to sort them by a certain feature (such as their colour). After the rule is learned, the subjects, without warning, are required to 'shift set' and sort them by a different feature (such as the shape of the symbols). People with prefrontal cortex lesions show impaired performance on this task and 'perseverate' — they carry on sorting the cards by a particular feature despite being told that it is incorrect.

FLUID INTELLIGENCE

The ability to reason rapidly about new problems, as contrasted with crystallized intelligence, which involves the use of previously acquired semantic or procedural knowledge.

HAEMODYNAMIC RESPONSE FUNCTION

The time course of changes in blood flow, volume and oxygenation level that occur in the brain in response to neural activity.

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Hedden, T., Gabrieli, J. Insights into the ageing mind: a view from cognitive neuroscience. Nat Rev Neurosci 5, 87–96 (2004). https://doi.org/10.1038/nrn1323

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