Abstract
Alzheimer’s disease (AD) is the leading cause of dementia worldwide. Due to demographic change in higher income countries and rising life expectancy in middle- and low-income countries, the prevalence of AD will increase significantly in the coming years. In the search for effective AD prevention, the role of stress in the development of AD has come into focus. There is increasing evidence that chronic exposure to stress is a risk factor for AD and may also adversely affect the course of the disease. In our review, we present the current literature on the association of specific personality traits and the risk of developing AD. We also report on findings on dementia risk in patients with posttraumatic stress disorder. Furthermore, we describe the role of anxiety symptoms in AD and give a brief overview over the biological mechanisms behind the association of stress and AD.
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References
Albert MS, DeKosky ST, Dickson D et al (2011) The diagnosis of mild cognitive impairment due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimer’s Dement 7:270–279. https://doi.org/10.1016/j.jalz.2011.03.008
Alzheimer’s Disease International (2015) World Alzheimer Report 2015, the global impact of dementia: an analysis of prevalence, incidence, cost and trends. Alzheimer’s Disease International, London
American Psychiatric Association (ed) (2013) Diagnostic and statistical manual of mental disorders: DSM-5, 5th edn. American Psychiatric Association, Washington, D.C
Bateman RJ, Xiong C, Benzinger TLS et al (2012) Clinical and biomarker changes in dominantly inherited Alzheimer’s disease. N Engl J Med 367:795–804. https://doi.org/10.1056/NEJMoa1202753
Braak H, Del Tredici K (2015) The preclinical phase of the pathological process underlying sporadic Alzheimer’s disease. Brain 138:2814–2833. https://doi.org/10.1093/brain/awv236
Breslau N, Schultz L (2013) Neuroticism and post-traumatic stress disorder: a prospective investigation. Psychol Med 43:1697–1702. https://doi.org/10.1017/S0033291712002632
Brodaty H, Heffernan M, Draper B et al (2012) Neuropsychiatric symptoms in older people with and without cognitive impairment. J Alzheimer’s Dis 31:411–420. https://doi.org/10.3233/JAD-2012-120169
Chaudieu I, Beluche I, Norton J et al (2008) Abnormal reactions to environmental stress in elderly persons with anxiety disorders: evidence from a population study of diurnal cortisol changes. J Affect Disord 106:307–313. https://doi.org/10.1016/j.jad.2007.07.025
Costantini D, Marasco V, Møller AP (2011) A meta-analysis of glucocorticoids as modulators of oxidative stress in vertebrates. J Comp Physiol B. https://doi.org/10.1007/s00360-011-0566-2
Csernansky JG, Dong H, Fagan AM et al (2006) Plasma cortisol and progression of dementia in subjects with Alzheimer-type dementia. Am J Psychiatry 163:2164–2169. https://doi.org/10.1176/ajp.2006.163.12.2164
de Kloet CS, Vermetten E, Geuze E et al (2006) Assessment of HPA-axis function in posttraumatic stress disorder: pharmacological and non-pharmacological challenge tests, a review. J Psychiatr Res 40:550–567. https://doi.org/10.1016/j.jpsychires.2005.08.002
Donovan NJ, Locascio JJ, Marshall GA et al (2018) Longitudinal association of amyloid beta and anxious-depressive symptoms in cognitively normal older adults. Am J Psychiatry. https://doi.org/10.1176/appi.ajp.2017.17040442
Ennis GE, An Y, Resnick SM et al (2017) Long-term cortisol measures predict Alzheimer disease risk. Neurology 88:371–378. https://doi.org/10.1212/WNL.0000000000003537
Flatt JD, Gilsanz P, Quesenberry CPJ et al (2018) Post-traumatic stress disorder and risk of dementia among members of a health care delivery system. Alzheimers Dement 14:28–34. https://doi.org/10.1016/j.jalz.2017.04.014
Garcia-Banda G, Chellew K, Fornes J et al (2014) Neuroticism and cortisol: pinning down an expected effect. Int J Psychophysiol 91:132–138. https://doi.org/10.1016/j.ijpsycho.2013.12.005
Geda YE, Roberts RO, Knopman DS et al (2008) Prevalence of neuropsychiatric symptoms in mild cognitive impairment and normal cognitive aging: population-based study. Arch Gen Psychiatry 65:1193. https://doi.org/10.1001/archpsyc.65.10.1193
Geda YE, Roberts RO, Mielke MM et al (2014) Baseline neuropsychiatric symptoms and the risk of incident mild cognitive impairment: a population-based study. Am J Psychiatry 171:572–581. https://doi.org/10.1176/appi.ajp.2014.13060821
Gil-Bea FJ, Aisa B, Solomon A et al (2010) HPA axis dysregulation associated to apolipoprotein E4 genotype in Alzheimer’s disease. J Alzheimers Dis 22:829–838. https://doi.org/10.3233/JAD-2010-100663
Green KN (2006) Glucocorticoids increase amyloid-beta and tau pathology in a mouse model of Alzheimer’s disease. J Neurosci 26:9047–9056. https://doi.org/10.1523/JNEUROSCI.2797-06.2006
Hanseeuw BJ, Jonas V, Jackson J et al (2018) Association of anxiety with subcortical amyloidosis in cognitively normal older adults. Mol Psychiatry. https://doi.org/10.1038/s41380-018-0214-2
Harris-White ME, Chu T, Miller SA et al (2001) Estrogen (E2) and glucocorticoid (Gc) effects on microglia and Ab clearance in vitro and in vivo. Neurochem Int 14:435
Herman JP, McKlveen JM, Ghosal S et al (2016) Regulation of the hypothalamic–pituitary–adrenocortical stress response. In: Terjung R (ed) Comprehensive physiology. Wiley, Hoboken, pp 603–621
Hettema JM, Neale MC, Myers JM et al (2006) A population-based twin study of the relationship between neuroticism and internalizing disorders. Am J Psychiatry 8:857
Jack CR, Bennett DA, Blennow K et al (2018) NIA-AA research framework: toward a biological definition of Alzheimer’s disease. Alzheimer’s Dement 14:535–562. https://doi.org/10.1016/j.jalz.2018.02.018
Jansen WJ, Ossenkoppele R, Knol DL et al (2015) Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis. JAMA 313:1924. https://doi.org/10.1001/jama.2015.4668
Johansson L, Guo X, Duberstein PR et al (2014) Midlife personality and risk of Alzheimer disease and distress: a 38-year follow-up. Neurology 83:1538–1544. https://doi.org/10.1212/WNL.0000000000000907
Kamat PK, Kalani A, Rai S et al (2016) Mechanism of oxidative stress and synapse dysfunction in the pathogenesis of Alzheimer’s disease: understanding the therapeutics strategies. Mol Neurobiol 53:648–661. https://doi.org/10.1007/s12035-014-9053-6
Kendler KS, Myers J (2010) The genetic and environmental relationship between major depression and the five-factor model of personality. Psychol Med 40:801. https://doi.org/10.1017/S0033291709991140
Li X-X, Li Z (2018) The impact of anxiety on the progression of mild cognitive impairment to dementia in Chinese and English data bases: a systematic review and meta-analysis. Int J Geriatr Psychiatry 33:131–140. https://doi.org/10.1002/gps.4694
Lyketsos CG, Lopez O, Jones B et al (2002) Prevalence of neuropsychiatric symptoms in dementia and mild cognitive impairment: results from the cardiovascular health study. JAMA 288:1475. https://doi.org/10.1001/jama.288.12.1475
Mawanda F, Wallace RB, McCoy K, Abrams TE (2017) PTSD, psychotropic medication use, and the risk of dementia among US veterans: a retrospective cohort study. J Am Geriatr Soc 65:1043–1050. https://doi.org/10.1111/jgs.14756
McKhann GM, Knopman DS, Chertkow H et al (2011) The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimer’s Dement 7:263–269. https://doi.org/10.1016/j.jalz.2011.03.005
Meziab O, Kirby KA, Williams B et al (2014) Prisoner of war status, posttraumatic stress disorder, and dementia in older veterans. Alzheimers Dement 10:S236–S241. https://doi.org/10.1016/j.jalz.2014.04.004
Peavy GM, Salmon DP, Jacobson MW et al (2009) Effects of chronic stress on memory decline in cognitively normal and mildly impaired older adults. Am J Psychiatry 166:1384–1391. https://doi.org/10.1176/appi.ajp.2009.09040461
Perin S, Harrington KD, Lim YY et al (2018) Amyloid burden and incident depressive symptoms in preclinical Alzheimer’s disease. J Affect Disord 229:269–274. https://doi.org/10.1016/j.jad.2017.12.101
Petkus AJ, Reynolds CA, Wetherell JL et al (2016) Anxiety is associated with increased risk of dementia in older Swedish twins. Alzheimers Dement 12:399–406. https://doi.org/10.1016/j.jalz.2015.09.008
Pietrzak RH, Lim YY, Neumeister A et al (2015) Amyloid-beta, anxiety, and cognitive decline in preclinical Alzheimer disease: a multicenter, prospective cohort study. JAMA Psychiatry 72:284–291. https://doi.org/10.1001/jamapsychiatry.2014.2476
Pocnet C, Rossier J, Antonietti J-P, von Gunten A (2011) Personality changes in patients with beginning Alzheimer disease. Can J Psychiatry 56:408–417. https://doi.org/10.1177/070674371105600704
Popp J, Wolfsgruber S, Heuser I et al (2015) Cerebrospinal fluid cortisol and clinical disease progression in MCI and dementia of Alzheimer’s type. Neurobiol Aging 36:601–607. https://doi.org/10.1016/j.neurobiolaging.2014.10.031
Qiu C, De Ronchi D, Fratiglioni L (2007) The epidemiology of the dementias: an update. Curr Opin Psychiatry 20:380–385. https://doi.org/10.1097/YCO.0b013e32816ebc7b
Qureshi SU, Kimbrell T, Pyne JM et al (2010) Greater prevalence and incidence of dementia in older veterans with posttraumatic stress disorder. J Am Geriatr Soc 58:1627–1633. https://doi.org/10.1111/j.1532-5415.2010.02977.x
Robins Wahlin T-B, Byrne GJ (2011) Personality changes in Alzheimer’s disease: a systematic review. Int J Geriatr Psychiatry 26:1019–1029. https://doi.org/10.1002/gps.2655
Roughead EE, Pratt NL, Kalisch Ellett LM et al (2017) Posttraumatic stress disorder, antipsychotic use and risk of dementia in veterans. J Am Geriatr Soc 65:1521–1526. https://doi.org/10.1111/jgs.14837
Savva GM, Zaccai J, Matthews FE et al (2009) Prevalence, correlates and course of behavioural and psychological symptoms of dementia in the population. Br J Psychiatry 194:212–219. https://doi.org/10.1192/bjp.bp.108.049619
Schiavone S, Jaquet V, Trabace L, Krause K-H (2013) Severe life stress and oxidative stress in the brain: from animal models to human pathology. Antioxid Redox Signal 18:1475–1490. https://doi.org/10.1089/ars.2012.4720
Schrijvers EMC, Direk N, Koudstaal PJ et al (2011) Associations of serum cortisol with cognitive function and dementia: the Rotterdam study. J Alzheimer’s Dis 25:671–677. https://doi.org/10.3233/JAD-2011-110224
Scott JC, Matt GE, Wrocklage KM et al (2015) A quantitative meta-analysis of neurocognitive functioning in posttraumatic stress disorder. Psychol Bull 141:105–140. https://doi.org/10.1037/a0038039
Sotiropoulos I, Catania C, Pinto LG et al (2011) Stress acts cumulatively to precipitate Alzheimer’s disease-like tau pathology and cognitive deficits. J Neurosci 31:7840–7847. https://doi.org/10.1523/JNEUROSCI.0730-11.2011
Sperling RA, Aisen PS, Beckett LA et al (2011) Toward defining the preclinical stages of Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimer’s Dement 7:280–292. https://doi.org/10.1016/j.jalz.2011.03.003
Starkstein SE, Jorge R, Petracca G, Robinson RG (2007) The construct of generalized anxiety disorder in Alzheimer disease. Am J Geriatr Psychiatry 15:42–49. https://doi.org/10.1097/01.JGP.0000229664.11306.b9
Terracciano A, Iacono D, O’Brien RJ et al (2013) Personality and resilience to Alzheimer’s disease neuropathology: a prospective autopsy study. Neurobiol Aging 34:1045–1050. https://doi.org/10.1016/j.neurobiolaging.2012.08.008
Terracciano A, Sutin AR, An Y et al (2014) Personality and risk of Alzheimer’s disease: new data and meta-analysis. Alzheimers Dement 10:179–186. https://doi.org/10.1016/j.jalz.2013.03.002
Terracciano A, An Y, Sutin AR et al (2017) Personality change in the preclinical phase of Alzheimer disease. JAMA Psychiatry 74:1259–1265. https://doi.org/10.1001/jamapsychiatry.2017.2816
Wadsworth LP, Lorius N, Donovan NJ et al (2012) Neuropsychiatric symptoms and global functional impairment along the Alzheimer’s Continuum. Dement Geriatr Cogn Disord 34:96–111. https://doi.org/10.1159/000342119
Wang T-Y, Wei H-T, Liou Y-J et al (2016) Risk for developing dementia among patients with posttraumatic stress disorder: a nationwide longitudinal study. J Affect Disord 205:306–310. https://doi.org/10.1016/j.jad.2016.08.013
Wilson RS, Evans DA, Bienias JL et al (2003) Proneness to psychological distress is associated with risk of Alzheimer’s disease. Neurology 61:1479–1485. https://doi.org/10.1212/01.WNL.0000096167.56734.59
Wilson RS, Arnold SE, Schneider JA et al (2006) Chronic psychological distress and risk of Alzheimer’s disease in old age. Neuroepidemiology 27:143–153. https://doi.org/10.1159/000095761
Wilson RS, Begeny CT, Boyle PA et al (2011) Vulnerability to stress, anxiety, and development of dementia in old age. Am J Geriatr Psychiatry 19:327–334. https://doi.org/10.1097/JGP.0b013e31820119da
Yaffe K, Vittinghoff E, Lindquist K et al (2010) Posttraumatic stress disorder and risk of dementia among US veterans. Arch Gen Psychiatry 67:608–613. https://doi.org/10.1001/archgenpsychiatry.2010.61
Zhao Q-F, Tan L, Wang H-F et al (2016) The prevalence of neuropsychiatric symptoms in Alzheimer’s disease: systematic review and meta-analysis. J Affect Disord 190:264–271. https://doi.org/10.1016/j.jad.2015.09.069
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F.J. reports Grant support from Eli Lilly, and personal fees for consultancy from Eli Lilly, Roche, Merck, Janssen Pharmaceutica, Biogen, Danone and AC Immune. All other authors declare that they have no conflict of interest.
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Escher, C.M., Sannemann, L. & Jessen, F. Stress and Alzheimer’s disease. J Neural Transm 126, 1155–1161 (2019). https://doi.org/10.1007/s00702-019-01988-z
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DOI: https://doi.org/10.1007/s00702-019-01988-z