Sex Differences in the Neural Correlates of Spatial Context Memory Decline in Healthy Aging

Aging is associated with episodic memory decline and alterations in memory-related brain function. However, it remains unclear if age-related memory decline is associated with similar patterns of brain aging in women and men. In the current task fMRI study, we tested the hypothesis that there are sex differences in the effect of age and memory performance on brain activity during episodic encoding and retrieval of face–location associations (spatial context memory). Forty-one women and 41 men between the ages of 21 and 76 years participated in this study. Between-group multivariate partial least squares analysis of the fMRI data was conducted to directly test for sex differences and similarities in age-related and performance-related patterns of brain activity. Our behavioral analysis indicated no significant sex differences in retrieval accuracy on the fMRI tasks. In relation to performance effects, we observed similarities and differences in how retrieval accuracy related to brain activity in women and men. Both sexes activated dorsal and lateral PFC, inferior parietal cortex, and left parahippocampal gyrus at encoding, and this supported subsequent memory performance. However, there were sex differences in retrieval activity in these same regions and in lateral occipital-temporal and ventrolateral PFC. In relation to age effects, we observed sex differences in the effect of age on memory-related activity within PFC, inferior parietal cortex, parahippocampal gyrus, and lateral occipital-temporal cortices. Overall, our findings suggest that the neural correlates of age-related spatial context memory decline differ in women compared with men.

[1]  M. Donahue,et al.  Vessel‐encoded arterial spin labeling (VE‐ASL) reveals elevated flow territory asymmetry in older adults with substandard verbal memory performance , 2014, Journal of magnetic resonance imaging : JMRI.

[2]  A R McIntosh,et al.  Frontotemporal interactions in face encoding and recognition. , 1999, Brain research. Cognitive brain research.

[3]  Cheryl L. Grady,et al.  Understanding variability in the BOLD signal and why it matters for aging , 2013, Brain Imaging and Behavior.

[4]  Mahzarin R. Banaji,et al.  Encoding-Specific Effects of Social Cognition on the Neural Correlates of Subsequent Memory , 2004, The Journal of Neuroscience.

[5]  R. Gur,et al.  Gender differences in aging: cognition, emotions, and neuroimaging studies , 2002, Dialogues in clinical neuroscience.

[6]  S. Cansino.  Episodic memory decay along the adult lifespan: a review of behavioral and neurophysiological evidence. , 2009, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[7]  Anthony Randal McIntosh,et al.  Partial least squares analysis of neuroimaging data: applications and advances , 2004, NeuroImage.

[8]  Jeffrey D. Johnson,et al.  Recollection and the reinstatement of encoding-related cortical activity. , 2007, Cerebral cortex.

[9]  K. Zilles,et al.  Coordinate‐based activation likelihood estimation meta‐analysis of neuroimaging data: A random‐effects approach based on empirical estimates of spatial uncertainty , 2009, Human brain mapping.

[10]  Marcia K. Johnson,et al.  Source monitoring 15 years later: what have we learned from fMRI about the neural mechanisms of source memory? , 2009, Psychological bulletin.

[11]  E. D. de Haan,et al.  Endogenous sex hormone levels and cognitive function in aging men , 2005, Neurology.

[12]  C Caltagirone,et al.  Age and sex differences in cerebral hemodynamics: a transcranial Doppler study. , 1998, Stroke.

[13]  W. Sommer,et al.  Sex differences in face cognition. , 2013, Acta psychologica.

[14]  Lin Ma,et al.  Use of 3D pseudo-continuous arterial spin labeling to characterize sex and age differences in cerebral blood flow , 2016, Neuroradiology.

[15]  R A Harshman,et al.  Sex differences in brain organization for verbal and non-verbal functions. , 1984, Progress in brain research.

[16]  Marcia K. Johnson,et al.  Source monitoring. , 1993, Psychological bulletin.

[17]  R. Gura,et al.  Sex di erences in brain-behavior relationships between verbal episodic memory and resting regional cerebral blood , 2015 .

[18]  Peiying Liu,et al.  Age-related differences in memory-encoding fMRI responses after accounting for decline in vascular reactivity , 2013, NeuroImage.

[19]  Eugene S. Edgington,et al.  Randomization Tests , 2011, International Encyclopedia of Statistical Science.

[20]  M. Rajah,et al.  Age-related changes in prefrontal cortex activity are associated with behavioural deficits in both temporal and spatial context memory retrieval in older adults , 2010, Cortex.

[21]  Julia Spaniol,et al.  Aging and the neural correlates of source memory: over-recruitment and functional reorganization , 2012, Neurobiology of Aging.

[22]  N. Makris,et al.  Reorganization of Functional Networks in Verbal Working Memory Circuitry in Early Midlife: The Impact of Sex and Menopausal Status , 2016, Cerebral cortex.

[23]  Robert Tibshirani,et al.  Bootstrap Methods for Standard Errors, Confidence Intervals, and Other Measures of Statistical Accuracy , 1986 .

[24]  E. Glisky,et al.  Double dissociation between item and source memory. , 1995 .

[25]  Thomas T. Liu,et al.  Cerebral blood flow and BOLD responses to a memory encoding task: A comparison between healthy young and elderly adults , 2007, NeuroImage.

[26]  S. Resnick,et al.  Longitudinal assessment of serum free testosterone concentration predicts memory performance and cognitive status in elderly men. , 2002, The Journal of clinical endocrinology and metabolism.

[27]  John A. E. Anderson,et al.  A multivariate analysis of age-related differences in default mode and task-positive networks across multiple cognitive domains. , 2010, Cerebral cortex.

[28]  Mark D'Esposito,et al.  Region-specific changes in prefrontal function with age: a review of PET and fMRI studies on working and episodic memory. , 2005, Brain : a journal of neurology.

[29]  Matthew L Senjem,et al.  Age, Sex, and APOE ε4 Effects on Memory, Brain Structure, and β-Amyloid Across the Adult Life Span. , 2015, JAMA neurology.

[30]  C. Oppenheim,et al.  Sex Differences in the Neural Correlates of Specific and General Autobiographical Memory , 2016, Frontiers in Human Neuroscience.

[31]  Roberto Cabeza,et al.  Aging Gracefully: Compensatory Brain Activity in High-Performing Older Adults , 2002, NeuroImage.

[32]  M. N. Rajah,et al.  Maintenance, reserve and compensation: the cognitive neuroscience of healthy ageing , 2018, Nature Reviews Neuroscience.

[33]  Lars-Göran Nilsson,et al.  Sex Differences in Cognition are Stable Over a 10-Year Period in Adulthood and Old Age , 2006, Neuropsychology, development, and cognition. Section B, Aging, neuropsychology and cognition.

[34]  M. Crossley,et al.  A male advantage for spatial and object but not verbal working memory using the n-back task , 2011, Brain and Cognition.

[35]  A. Herlitz,et al.  Verified Hormone Therapy Improves Episodic Memory Performance in Healthy Postmenopausal Women , 2006, Neuropsychology, development, and cognition. Section B, Aging, neuropsychology and cognition.

[36]  Elizabeth Hampson,et al.  Cognitive Pattern in Men and Women Is Influenced by Fluctuations in Sex Hormones , 1994 .

[37]  A. Dale,et al.  Selective averaging of rapidly presented individual trials using fMRI , 1997, Human brain mapping.

[38]  N. Makris,et al.  Impact of Sex and Menopausal Status on Episodic Memory Circuitry in Early Midlife , 2016, The Journal of Neuroscience.

[39]  G. Winocur,et al.  Age effects on social cognition: faces tell a different story. , 2006, Psychology and aging.

[40]  D. Bates,et al.  Fitting Linear Mixed-Effects Models Using lme4 , 2014, 1406.5823.

[41]  A. Loven.  Sex Differences in Cognitive Functions , 2009 .

[42]  N. Newcombe,et al.  The role of experience in spatial test performance: A meta-analysis , 1989 .

[43]  Jerzy Bodurka,et al.  Functional neuroimaging of sex differences in autobiographical memory recall , 2013, Human brain mapping.

[44]  F. Pelliccia,et al.  Time Since Menopause Influences the Acute and Chronic Effect of Estrogens on Endothelial Function , 2007, Arteriosclerosis, thrombosis, and vascular biology.

[45]  Raquel E Gur,et al.  Sex differences in brain-behavior relationships between verbal episodic memory and resting regional cerebral blood flow , 2000, Neuropsychologia.

[46]  Charles D. Smith,et al.  Partial least squares for discrimination in fMRI data. , 2012, Magnetic resonance imaging.

[47]  R Core Team,et al.  R: A language and environment for statistical computing. , 2014 .

[48]  M. D’Esposito,et al.  Alterations in the BOLD fMRI signal with ageing and disease: a challenge for neuroimaging , 2003, Nature Reviews Neuroscience.

[49]  M. Natasha Rajah,et al.  Changes in the modulation of brain activity during context encoding vs. context retrieval across the adult lifespan , 2016, NeuroImage.

[50]  Jemett L. Desmond,et al.  Semantic encoding and retrieval in the left inferior prefrontal cortex: a functional MRI study of task difficulty and process specificity , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[51]  Michael D. Rugg,et al.  Right dorsolateral prefrontal cortex is engaged during post-retrieval processing of both episodic and semantic information , 2009, Neuropsychologia.

[52]  E. Tulving.  Précis of Elements of episodic memory , 1984, Behavioral and Brain Sciences.

[53]  A meta-analysis of cortisol response to challenge in human aging: importance of gender , 2005, Psychoneuroendocrinology.

[54]  N. Raz,et al.  Differential effects of aging on memory for content and context: a meta-analysis. , 1995, Psychology and aging.

[55]  Charan Ranganath,et al.  Prefrontal Cortex and Long-Term Memory Encoding: An Integrative Review of Findings from Neuropsychology and Neuroimaging , 2007, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[56]  C. Pike,et al.  Brain levels of sex steroid hormones in men and women during normal aging and in Alzheimer's disease , 2011, Neurobiology of Aging.

[57]  J. Pruessner.  The interplay of sex and gender on the reactivity of the endocrine stress axis in humans , 2018, Current Opinion in Behavioral Sciences.

[58]  Michael D. Rugg,et al.  Overlap between the Neural Correlates of Cued Recall and Source Memory: Evidence for a Generic Recollection Network? , 2012, Journal of Cognitive Neuroscience.

[59]  Endel Tulving,et al.  Prefrontal cortex and episodic memory retrieval mode. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[60]  H Yonas,et al.  Increased stroke risk predicted by compromised cerebral blood flow reactivity. , 1993, Journal of neurosurgery.

[61]  A. Herlitz,et al.  Sex differences in episodic memory: the impact of verbal and visuospatial ability. , 1999, Neuropsychology.

[62]  I. Loy-English,et al.  Gender differences in dementia risk factors. , 2007, Gender medicine.

[63]  R. Cabeza,et al.  Effects of aging on the neural correlates of successful item and source memory encoding. , 2008, Journal of experimental psychology. Learning, memory, and cognition.

[64]  A. Herlitz,et al.  Sex differences in episodic memory: Minimal influence of estradiol , 2003, Brain and Cognition.

[65]  A. Herlitz,et al.  Gender differences in episodic memory , 1997, Memory & cognition.

[66]  Selene Cansino,et al.  Neural correlates of source memory retrieval in young, middle-aged and elderly adults , 2012, Biological Psychology.

[67]  Philippe Fossati,et al.  Modulation of Memory Formation by Stimulus Content: Specific Role of the Medial Prefrontal Cortex in the Successful Encoding of Social Pictures , 2007, Journal of Cognitive Neuroscience.

[68]  Andreas Papassotiropoulos,et al.  Sex-Dependent Dissociation between Emotional Appraisal and Memory: A Large-Scale Behavioral and fMRI Study , 2015, The Journal of Neuroscience.

[69]  L Nyberg,et al.  Brain activation during episodic memory retrieval: sex differences. , 2000, Acta psychologica.

[70]  M. Rajah,et al.  Age-related changes in frequency of mind-wandering and task-related interferences during memory encoding and their impact on retrieval , 2013, Memory.

[71]  C. Lawton.  Gender differences in way-finding strategies: Relationship to spatial ability and spatial anxiety , 1994 .

[72]  Cinthya Estrada-Manilla,et al.  Brain activity during source memory retrieval in young, middle-aged and old adults , 2015, Brain Research.

[73]  Cinthya Estrada-Manilla,et al.  fMRI subsequent source memory effects in young, middle-aged and old adults , 2015, Behavioural Brain Research.

[74]  Alzheimer's Association∗.  2019 Alzheimer's disease facts and figures , 2019, Alzheimer's & Dementia.

[75]  Deanna M. Barch,et al.  Sex influences on material-sensitive functional lateralization in working and episodic memory: Men and women are not all that different , 2006, NeuroImage.

[76]  Agneta Herlitz,et al.  Sex differences in episodic memory: The impact of verbal and visuospatial ability. , 1999 .

[77]  S. Studenski,et al.  Bioavailable Testosterone Linearly Declines Over A Wide Age Spectrum in Men and Women From The Baltimore Longitudinal Study of Aging. , 2016, The journals of gerontology. Series A, Biological sciences and medical sciences.

[78]  Nicole M. Long,et al.  Modulation of Task Demands Suggests That Semantic Processing Interferes With the Formation of Episodic Associations , 2017, Journal of experimental psychology. Learning, memory, and cognition.

[79]  C. Grady.  Cognitive Neuroscience of Aging , 2008, Annals of the New York Academy of Sciences.

[80]  C. Pike,et al.  Androgen regulation of β-amyloid protein and the risk of Alzheimer's disease , 2008, Brain Research Reviews.

[81]  S. Cansino,et al.  Age-related changes in neural activity during source memory encoding in young, middle-aged and elderly adults , 2010, Neuropsychologia.

[82]  Yaakov Stern,et al.  Separating function from structure in perfusion imaging of the aging brain , 2009, Human brain mapping.

[83]  R. Cabeza,et al.  Imaging Cognition: An Empirical Review of PET Studies with Normal Subjects , 1997, Journal of Cognitive Neuroscience.

[84]  E. Ankudowich,et al.  Changes in the correlation between spatial and temporal source memory performance and BOLD activity across the adult lifespan , 2017, Cortex.

[85]  P. Vemuri,et al.  Clinical epidemiology of Alzheimer’s disease: assessing sex and gender differences , 2014, Clinical epidemiology.

[86]  L. Jacoby,et al.  Cognitive and neural effects of semantic encoding strategy training in older adults. , 2012, Cerebral cortex.

[87]  M. D’Esposito,et al.  Reducing vascular variability of fMRI data across aging populations using a breathholding task , 2007, Human brain mapping.

[88]  C J Hamilton,et al.  Beyond sex differences in visuo-spatial processing: the impact of gender trait possession. , 1995, British journal of psychology.

[89]  C. Lewin,et al.  Sex differences favoring women in verbal but not in visuospatial episodic memory. , 2001, Neuropsychology.

[90]  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.

[91]  D. Schacter,et al.  The relation between source memory and aging. , 1991, Psychology and aging.

[92]  J. Goldstein,et al.  Sex differences in episodic memory in early midlife: impact of reproductive aging , 2017, Menopause.

[93]  D Friedman,et al.  Item and source memory: differential age effects revealed by event‐related potentials , 1997, Neuroreport.

[94]  M. J. Sharps,et al.  Spatial Cognition and Gender , 1994 .

[95]  Florin Dolcos,et al.  Attention-related activity during episodic memory retrieval: a cross-function fMRI study , 2003, Neuropsychologia.

[96]  Albert Postma,et al.  Sex Differences in Object Location Memory , 1998, Brain and Cognition.

[97]  Michael R. Dulas,et al.  Aging Affects the Interaction between Attentional Control and Source Memory: An fMRI Study , 2014, Journal of Cognitive Neuroscience.

[98]  C. Friedenreich,et al.  Effects of cardiorespiratory fitness and cerebral blood flow on cognitive outcomes in older women , 2010, Neurobiology of Aging.

[99]  V. Henderson.  Action of estrogens in the aging brain: dementia and cognitive aging. , 2010, Biochimica et biophysica acta.

[100]  R. Cabeza,et al.  Imaging Cognition II: An Empirical Review of 275 PET and fMRI Studies , 2000, Journal of Cognitive Neuroscience.

[101]  Per B. Brockhoff,et al.  lmerTest Package: Tests in Linear Mixed Effects Models , 2017 .

[102]  D. Jolley,et al.  Cost benefits of a medically supervised day treatment program for patients with Alzheimer's disease and other forms of dementia , 1989 .

[103]  M. Natasha Rajah,et al.  Similarities in the patterns of prefrontal cortex activity during spatial and temporal context memory retrieval after equating for task structure and performance , 2011, NeuroImage.

[104]  M. Torrens.  Co-Planar Stereotaxic Atlas of the Human Brain—3-Dimensional Proportional System: An Approach to Cerebral Imaging, J. Talairach, P. Tournoux. Georg Thieme Verlag, New York (1988), 122 pp., 130 figs. DM 268 , 1990 .

[105]  Dirk H. Hellhammer,et al.  OPPOSING EFFECTS OF DHEA REPLACEMENT IN ELDERLY SUBJECTS ON DECLARATIVE MEMORY AND ATTENTION AFTER EXPOSURE TO A LABORATORY STRESSOR , 1998, Psychoneuroendocrinology.

[106]  Michael J. Martinez,et al.  Bias between MNI and Talairach coordinates analyzed using the ICBM‐152 brain template , 2007, Human brain mapping.

[107]  Florin Dolcos,et al.  Similarities and Differences in the Neural Correlates of Episodic Memory Retrieval and Working Memory , 2002, NeuroImage.

[108]  J. Morrison,et al.  Estrogen, Menopause, and the Aging Brain: How Basic Neuroscience Can Inform Hormone Therapy in Women , 2006, The Journal of Neuroscience.

[109]  J. V. Haxby,et al.  Spatial Pattern Analysis of Functional Brain Images Using Partial Least Squares , 1996, NeuroImage.

[110]  Audrey Duarte,et al.  The effects of aging on material-independent and material-dependent neural correlates of source memory retrieval. , 2012, Cerebral cortex.

[111]  David Maillet,et al.  Context Memory Decline in Middle Aged Adults is Related to Changes in Prefrontal Cortex Function. , 2016, Cerebral cortex.

[112]  R. C. Oldfield.  THE ASSESSMENT AND ANALYSIS OF HANDEDNESS , 1971 .

[113]  Andrew L. Mackinnon,et al.  Estimation de l’intelligence prémorbide chez les francophones , 2005 .

[114]  Bart Rypma,et al.  Neural and vascular variability and the fMRI-BOLD response in normal aging. , 2010, Magnetic resonance imaging.

[115]  A. Herlitz,et al.  Sex Differences in Episodic Memory , 2008 .

[116]  C. Grady,et al.  Event-related fMRI studies of episodic encoding and retrieval: Meta-analyses using activation likelihood estimation , 2009, Neuropsychologia.

[117]  H. Spiers,et al.  Prefrontal and medial temporal lobe interactions in long-term memory , 2003, Nature Reviews Neuroscience.

[118]  M. Mapstone,et al.  Memory complaints and memory performance in the menopausal transition , 2009, Menopause.

[119]  Lila Davachi,et al.  Behavioral / Systems / Cognitive Differential Encoding Mechanisms for Subsequent Associative Recognition and Free Recall , 2012 .

[120]  Roberto Cabeza,et al.  Gender differences in autobiographical memory for everyday events: Retrieval elicited by SenseCam images versus verbal cues , 2011, Memory.

[121]  E. Metter,et al.  Longitudinal effects of aging on serum total and free testosterone levels in healthy men. Baltimore Longitudinal Study of Aging. , 2001, The Journal of clinical endocrinology and metabolism.

[122]  Marcia K. Johnson,et al.  Age-related differences in agenda-driven monitoring of format and task information , 2013, Neuropsychologia.

[123]  L. Newby,et al.  Age Moderates the Short-Term Effects of Transdermal 17β-Estradiol on Endothelium-Dependent Vascular Function in Postmenopausal Women , 2007, Arteriosclerosis, thrombosis, and vascular biology.

[124]  Andrew R. Bender,et al.  Associative deficit in recognition memory in a lifespan sample of healthy adults. , 2010, Psychology and aging.

[125]  R. C. Oldfield.  The assessment and analysis of handedness: the Edinburgh inventory. , 1971, Neuropsychologia.

[126]  Rena Li,et al.  Brain sex matters: Estrogen in cognition and Alzheimer’s disease , 2014, Molecular and Cellular Endocrinology.

[127]  A. R. McIntosh,et al.  Spatiotemporal analysis of event-related fMRI data using partial least squares , 2004, NeuroImage.

[128]  C. Ranganath,et al.  The Dorsolateral Prefrontal Cortex Contributes to Successful Relational Memory Encoding , 2007, The Journal of Neuroscience.