Effect of purpose in life on the relation between Alzheimer disease pathologic changes on cognitive function in advanced age.

CONTEXT Purpose in life is associated with a substantially reduced risk of Alzheimer disease (AD), but the neurobiologic basis of this protective effect remains unknown. OBJECTIVE To test the hypothesis that purpose in life reduces the deleterious effects of AD pathologic changes on cognition in advanced age. DESIGN A longitudinal, epidemiologic, clinicopathologic study of aging was conducted that included detailed annual clinical evaluations and brain autopsy. PARTICIPANTS Two hundred forty-six community-based older persons from the Rush Memory and Aging Project participated. MAIN OUTCOME MEASURES Purpose in life was assessed via structured interview, and cognitive function was evaluated annually and proximate to death. On postmortem examination, 3 indexes of AD pathologic features were quantified: global AD pathologic changes, amyloid, and tangles. The associations of disease pathologic changes and purpose in life with cognition were examined using linear regression and mixed models. RESULTS Purpose in life modified the association between the global measure of AD pathologic changes and cognition (mean [SE] parameter estimate, 0.532 [0.211]; P = .01), such that participants who reported higher levels of purpose in life exhibited better cognitive function despite the burden of the disease. Purpose in life also reduced the association of tangles with cognition (parameter estimate, 0.042 [0.019]; P = .03), and the protective effect of purpose in life persisted even after controlling for several potentially confounding variables. Furthermore, in analyses examining whether purpose in life modified the association between AD pathologic effects and the rate of cognitive decline, we found that higher levels of purpose in life reduced the effect of AD pathologic changes on cognitive decline (parameter estimate, 0.085 [0.039]; P = .03). CONCLUSION Higher levels of purpose in life reduce the deleterious effects of AD pathologic changes on cognition in advanced age.

[1]  M. Viitanen,et al.  Cognitive reserve hypothesis: Pittsburgh Compound B and fluorodeoxyglucose positron emission tomography in relation to education in mild Alzheimer's disease , 2008, Annals of neurology.

[2]  Roger L. Brown,et al.  Psychosocial predictors of changing sleep patterns in aging women: a multiple pathway approach. , 2010, Psychology and aging.

[3]  J. Schneider,et al.  Neuropathology of older persons without cognitive impairment from two community-based studies , 2006, Neurology.

[4]  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.

[5]  D. Bennett,et al.  Education modifies the association of amyloid but not tangles with cognitive function , 2005, Neurology.

[6]  J. Schneider,et al.  The effect of social networks on the relation between Alzheimer's disease pathology and level of cognitive function in old people: a longitudinal cohort study , 2006, The Lancet Neurology.

[7]  R. Adolphs,et al.  The social brain: neural basis of social knowledge. , 2009, Annual review of psychology.

[8]  J. Schneider,et al.  Education modifies the relation of AD pathology to level of cognitive function in older persons , 2003, Neurology.

[9]  Keith A. Johnson,et al.  Cognition, Reserve, and Amyloid Deposition in Normal Aging , 2009, Annals of neurology.

[10]  U. Lindenberger,et al.  Well-being affects changes in perceptual speed in advanced old age: longitudinal evidence for a dynamic link. , 2007, Developmental psychology.

[11]  B. Singer,et al.  Psychological well-being: meaning, measurement, and implications for psychotherapy research. , 1996, Psychotherapy and psychosomatics.

[12]  Rosemarie A. Martin,et al.  Purpose in life predicts treatment outcome among adult cocaine abusers in treatment. , 2011, Journal of substance abuse treatment.

[13]  David A. Bennett,et al.  The Rush Memory and Aging Project: Study Design and Baseline Characteristics of the Study Cohort , 2005, Neuroepidemiology.

[14]  C. Keyes,et al.  The structure of psychological well-being revisited. , 1995, Journal of personality and social psychology.

[15]  D. Bennett,et al.  Correlates of Life Space in a Volunteer Cohort of Older Adults , 2007, Experimental aging research.

[16]  David A. Bennett,et al.  Postmortem Indices Linking Risk Factors to Cognition: Results From the Religious Order Study and the Memory and Aging Project , 2006, Alzheimer disease and associated disorders.

[17]  D. Bennett,et al.  Early and late life cognitive activity and cognitive systems in old age , 2005, Journal of the International Neuropsychological Society.

[18]  David A Bennett,et al.  Purpose in Life Is Associated With Mortality Among Community-Dwelling Older Persons , 2009, Psychosomatic medicine.

[19]  Yaakov Stern,et al.  Cognitive Reserve and Lifestyle , 2003, Journal of clinical and experimental neuropsychology.

[20]  B. Winblad,et al.  Influence of social network on occurrence of dementia: a community-based longitudinal study , 2000, The Lancet.

[21]  Heather L. Urry,et al.  Social relationships, sleep quality, and interleukin-6 in aging women. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[22]  D. Bennett,et al.  Processing resources reduce the effect of Alzheimer pathology on other cognitive systems , 2008, Neurology.

[23]  M. Mintun,et al.  Alzheimer disease and cognitive reserve: variation of education effect with carbon 11-labeled Pittsburgh Compound B uptake. , 2008, Archives of neurology.

[24]  David A Bennett,et al.  Effect of a purpose in life on risk of incident Alzheimer disease and mild cognitive impairment in community-dwelling older persons. , 2010, Archives of general psychiatry.

[25]  D. Bennett,et al.  The neuropathology of older persons with and without dementia from community versus clinic cohorts. , 2009, Journal of Alzheimer's disease : JAD.

[26]  Jeffrey A. James,et al.  Frequent amyloid deposition without significant cognitive impairment among the elderly. , 2008, Archives of neurology.

[27]  D. Bennett,et al.  Purpose in life is associated with a reduced risk of incident disability among community-dwelling older persons. , 2010, The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry.

[28]  J. Schneider,et al.  Chronic Distress, Age-Related Neuropathology, and Late-Life Dementia , 2007, Psychosomatic medicine.

[29]  C. Ryff,et al.  Personality and well-being: reexamining methods and meanings. , 1997, Journal of personality and social psychology.

[30]  M. Folstein,et al.  Clinical diagnosis of Alzheimer's disease: Report of the NINCDS—ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease , 2011, Neurology.

[31]  Keith A. Johnson,et al.  Neuropathology of Cognitively Normal Elderly , 2003, Journal of neuropathology and experimental neurology.

[32]  W. Markesbery,et al.  Alzheimer's neurofibrillary pathology and the spectrum of cognitive function: Findings from the Nun Study , 2002, Annals of neurology.

[33]  Y. Gustafson,et al.  Purpose in Life among Men and Women Aged 85 Years and Older , 2010, International journal of aging & human development.

[34]  Richard J. Davidson,et al.  Psychological Well-Being and Ill-Being: Do They Have Distinct or Mirrored Biological Correlates? , 2006, Psychotherapy and Psychosomatics.

[35]  J. Morrison,et al.  Tangle and neuron numbers, but not amyloid load, predict cognitive status in Alzheimer’s disease , 2003, Neurology.

[36]  Karen M. Gosche,et al.  Very Early Detection of Alzheimer Neuropathology and the Role of Brain Reserve in Modifying Its Clinical Expression , 2005, Journal of geriatric psychiatry and neurology.

[37]  G. Westerhof,et al.  Improvement in personal meaning mediates the effects of a life review intervention on depressive symptoms in a randomized controlled trial. , 2010, The Gerontologist.

[38]  D. Bennett,et al.  Depressive symptoms, clinical AD, and cortical plaques and tangles in older persons , 2003, Neurology.

[39]  V. Frankl,et al.  Man's search for meaning: An introduction to logotherapy, 4th ed. , 1992 .

[40]  D. Bennett,et al.  Chronic distress and incidence of mild cognitive impairment , 2007, Neurology.

[41]  R. Adolphs.  The neurobiology of social cognition , 2001, Current Opinion in Neurobiology.

[42]  Patrick E. McKnight,et al.  Purpose in Life as a System that Creates and Sustains Health and Well-Being: An Integrative, Testable Theory , 2009 .

[43]  David A. Bennett,et al.  Decision Rules Guiding the Clinical Diagnosis of Alzheimer’s Disease in Two Community-Based Cohort Studies Compared to Standard Practice in a Clinic-Based Cohort Study , 2006, Neuroepidemiology.

[44]  M. Pinquart.  Creating and maintaining purpose in life in old age: A meta-analysis , 2002 .

[45]  A. Wood,et al.  The absence of positive psychological (eudemonic) well-being as a risk factor for depression: a ten year cohort study. , 2010, Journal of affective disorders.

[46]  D. Bennett,et al.  Mild cognitive impairment: risk of Alzheimer disease and rate of cognitive decline. , 2006, Neurology.

[47]  Yaakov Stern,et al.  Cognitive Reserve: Implications for Assessment and Intervention , 2013, Folia Phoniatrica et Logopaedica.

[48]  Denise C. Park,et al.  Beta-Amyloid Deposition and the Aging Brain , 2009, Neuropsychology Review.

[49]  Lull Gf,et al.  THE AMERICAN MEDICAL ASSOCIATION. , 1947, Science.

[50]  Charles D. Smith,et al.  Preclinical AD Workgroup staging: pathological correlates and potential challenges , 2012, Neurobiology of Aging.

[51]  Yaakov Stern,et al.  Association of life activities with cerebral blood flow in Alzheimer disease: implications for the cognitive reserve hypothesis. , 2003, Archives of neurology.

[52]  J. Morris,et al.  Education and reported onset of symptoms among individuals with Alzheimer disease. , 2008, Archives of neurology.

[53]  B. Singer,et al.  Positive health: connecting well-being with biology. , 2004, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[54]  F. Huppert,et al.  Psychometric evaluation and predictive validity of Ryff's psychological well-being items in a UK birth cohort sample of women , 2006, Health and quality of life outcomes.

[55]  David A Bennett,et al.  Conscientiousness and the incidence of Alzheimer disease and mild cognitive impairment. , 2007, Archives of general psychiatry.