Associations of Widowhood and β-Amyloid With Cognitive Decline in Cognitively Unimpaired Older Adults | Dementia and Cognitive Impairment | JAMA Network Open | JAMA Network
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1.
Patterson  C. World Alzheimer Report 2018: the state of the art of dementia research: new frontiers. https://www.alz.co.uk/research/WorldAlzheimerReport2018.pdf. Accessed January 17, 2020.
2.
Roberts  AW, Ogunwole  SU, Blakeslee  L, Rabe  MA. The population 65 years and older in the United States: 2016. https://www.census.gov/content/dam/Census/library/publications/2018/acs/ACS-38.pdf. Accessed January 17, 2020.
3.
Aartsen  MJ, van Tilburg  T, Smits  CH, Knipscheer  KCPM.  A longitudinal study of the impact of physical and cognitive decline on the personal network in old age.  J Soc Pers Relat. 2004;21(2):249-266. doi:10.1177/0265407504041386Google ScholarCrossref
4.
Karlamangla  AS, Miller-Martinez  D, Aneshensel  CS, Seeman  TE, Wight  RG, Chodosh  J.  Trajectories of cognitive function in late life in the United States: demographic and socioeconomic predictors.  Am J Epidemiol. 2009;170(3):331-342. doi:10.1093/aje/kwp154PubMedGoogle ScholarCrossref
5.
Shin  SH, Kim  G, Park  S.  Widowhood status as a risk factor for cognitive decline among older adults.  Am J Geriatr Psychiatry. 2018;26(7):778-787. doi:10.1016/j.jagp.2018.03.013PubMedGoogle ScholarCrossref
6.
Zhang  Z, Li  LW, Xu  H, Liu  J.  Does widowhood affect cognitive function among Chinese older adults?  SSM Popul Health. 2018;7:100329. doi:10.1016/j.ssmph.2018.100329PubMedGoogle Scholar
7.
Sommerlad  A, Ruegger  J, Singh-Manoux  A, Lewis  G, Livingston  G.  Marriage and risk of dementia: systematic review and meta-analysis of observational studies.  J Neurol Neurosurg Psychiatry. 2018;89(3):231-238. doi:10.1136/jnnp-2017-316274PubMedGoogle ScholarCrossref
8.
Sperling  RA, Aisen  PS, Beckett  LA,  et al.  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.  Alzheimers Dement. 2011;7(3):280-292. doi:10.1016/j.jalz.2011.03.003PubMedGoogle ScholarCrossref
9.
Jack  CR  Jr, Bennett  DA, Blennow  K,  et al; Contributors.  NIA-AA Research Framework: toward a biological definition of Alzheimer’s disease.  Alzheimers Dement. 2018;14(4):535-562. doi:10.1016/j.jalz.2018.02.018PubMedGoogle ScholarCrossref
10.
Burnham  SC, Bourgeat  P, Doré  V,  et al; AIBL Research Group.  Clinical and cognitive trajectories in cognitively healthy elderly individuals with suspected non-Alzheimer’s disease pathophysiology (SNAP) or Alzheimer’s disease pathology: a longitudinal study.  Lancet Neurol. 2016;15(10):1044-1053. doi:10.1016/S1474-4422(16)30125-9PubMedGoogle ScholarCrossref
11.
Donohue  MC, Sperling  RA, Petersen  R, Sun  CK, Weiner  MW, Aisen  PS; Alzheimer’s Disease Neuroimaging Initiative.  Association between elevated brain amyloid and subsequent cognitive decline among cognitively normal persons.  JAMA. 2017;317(22):2305-2316. doi:10.1001/jama.2017.6669PubMedGoogle ScholarCrossref
12.
Biddle  KD, d’Oleire Uquillas  F, Jacobs  HIL,  et al.  Social engagement and amyloid-β-related cognitive decline in cognitively normal older adults.  Am J Geriatr Psychiatry. 2019;27(11):1247-1256. doi:10.1016/j.jagp.2019.05.005PubMedGoogle ScholarCrossref
13.
Morris  JC.  The Clinical Dementia Rating (CDR): current version and scoring rules.  Neurology. 1993;43(11):2412-2414. doi:10.1212/WNL.43.11.2412-aPubMedGoogle ScholarCrossref
14.
Abikoff  H, Alvir  J, Hong  G,  et al.  Logical memory subtest of the Wechsler Memory Scale: age and education norms and alternate-form reliability of two scoring systems.  J Clin Exp Neuropsychol. 1987;9(4):435-448. doi:10.1080/01688638708405063PubMedGoogle ScholarCrossref
15.
Folstein  MF, Folstein  SE, McHugh  PR.  “Mini-Mental State”: a practical method for grading the cognitive state of patients for the clinician.  J Psychiatr Res. 1975;12(3):189-198. doi:10.1016/0022-3956(75)90026-6PubMedGoogle ScholarCrossref
16.
Yesavage  JA, Brink  TL, Rose  TL,  et al.  Development and validation of a Geriatric Depression Screening scale: a preliminary report.  J Psychiatr Res. 1982-1983;17(1):37-49. doi:10.1016/0022-3956(82)90033-4PubMedGoogle ScholarCrossref
17.
Mormino  EC, Papp  KV, Rentz  DM,  et al.  Early and late change on the preclinical Alzheimer’s cognitive composite in clinically normal older individuals with elevated amyloid β.  Alzheimers Dement. 2017;13(9):1004-1012. doi:10.1016/j.jalz.2017.01.018PubMedGoogle ScholarCrossref
18.
Weschler  D.  WMS-R Weschler Memory Scale Revised Manual. New York, NY: Harcourt Brace Jovanovich, Inc; 1987.
19.
Grober  E, Hall  C, Sanders  AE, Lipton  RB.  Free and cued selective reminding distinguishes Alzheimer’s disease from vascular dementia.  J Am Geriatr Soc. 2008;56(5):944-946. doi:10.1111/j.1532-5415.2008.01652.xPubMedGoogle ScholarCrossref
20.
Buckley  RF, Schultz  AP, Hedden  T,  et al.  Functional network integrity presages cognitive decline in preclinical Alzheimer disease.  Neurology. 2017;89(1):29-37. doi:10.1212/WNL.0000000000004059PubMedGoogle ScholarCrossref
21.
Hollingshead  AB.  Two Factor Index of Social Position. New Haven, CT: Yale University Press; 1957.
22.
D’Agostino  RB  Sr, Vasan  RS, Pencina  MJ,  et al.  General cardiovascular risk profile for use in primary care: the Framingham Heart Study.  Circulation. 2008;117(6):743-753. doi:10.1161/CIRCULATIONAHA.107.699579PubMedGoogle ScholarCrossref
23.
Rabin  JS, Schultz  AP, Hedden  T,  et al.  Interactive associations of vascular risk and β-amyloid burden with cognitive decline in clinically normal elderly individuals: findings from the Harvard Aging Brain Study.  JAMA Neurol. 2018;75(9):1124-1131. doi:10.1001/jamaneurol.2018.1123PubMedGoogle ScholarCrossref
24.
Stewart  AL, Mills  KM, King  AC, Haskell  WL, Gillis  D, Ritter  PL.  CHAMPS physical activity questionnaire for older adults: outcomes for interventions.  Med Sci Sports Exerc. 2001;33(7):1126-1141. doi:10.1097/00005768-200107000-00010PubMedGoogle ScholarCrossref
25.
Seeman  TE, Lusignolo  TM, Albert  M, Berkman  L.  Social relationships, social support, and patterns of cognitive aging in healthy, high-functioning older adults: MacArthur studies of successful aging.  Health Psychol. 2001;20(4):243-255. doi:10.1037/0278-6133.20.4.243PubMedGoogle ScholarCrossref
26.
Dale  AM, Fischl  B, Sereno  MI.  Cortical surface-based analysis: segmentation and surface reconstruction.  Neuroimage. 1999;9(2):179-194. doi:10.1006/nimg.1998.0395PubMedGoogle ScholarCrossref
27.
Fischl  B, Sereno  MI, Dale  AM.  Cortical surface-based analysis: inflation, flattening, and a surface-based coordinate system.  Neuroimage. 1999;9(2):195-207. doi:10.1006/nimg.1998.0396PubMedGoogle ScholarCrossref
28.
Jacobs  HIL, Hedden  T, Schultz  AP,  et al.  Structural tract alterations predict downstream tau accumulation in amyloid-positive older individuals.  Nat Neurosci. 2018;21(3):424-431. doi:10.1038/s41593-018-0070-zPubMedGoogle ScholarCrossref
29.
Mormino  EC, Betensky  RA, Hedden  T,  et al.  Synergistic effect of β-amyloid and neurodegeneration on cognitive decline in clinically normal individuals.  JAMA Neurol. 2014;71(11):1379-1385. doi:10.1001/jamaneurol.2014.2031PubMedGoogle ScholarCrossref
30.
Johnson  KA, Gregas  M, Becker  JA,  et al.  Imaging of amyloid burden and distribution in cerebral amyloid angiopathy.  Ann Neurol. 2007;62(3):229-234. doi:10.1002/ana.21164PubMedGoogle ScholarCrossref
31.
Price  JC, Klunk  WE, Lopresti  BJ,  et al.  Kinetic modeling of amyloid binding in humans using PET imaging and Pittsburgh Compound-B.  J Cereb Blood Flow Metab. 2005;25(11):1528-1547. doi:10.1038/sj.jcbfm.9600146PubMedGoogle ScholarCrossref
32.
Greve  DN, Svarer  C, Fisher  PM,  et al.  Cortical surface-based analysis reduces bias and variance in kinetic modeling of brain PET data.  Neuroimage. 2014;92:225-236. doi:10.1016/j.neuroimage.2013.12.021PubMedGoogle ScholarCrossref
33.
Hanseeuw  BJ, Betensky  RA, Schultz  AP,  et al.  Fluorodeoxyglucose metabolism associated with tau-amyloid interaction predicts memory decline.  Ann Neurol. 2017;81(4):583-596. doi:10.1002/ana.24910PubMedGoogle ScholarCrossref
34.
Holmes  TH, Rahe  RH.  The Social Readjustment Rating Scale.  J Psychosom Res. 1967;11(2):213-218. doi:10.1016/0022-3999(67)90010-4PubMedGoogle ScholarCrossref
35.
Fried  EI, Bockting  C, Arjadi  R,  et al.  From loss to loneliness: the relationship between bereavement and depressive symptoms.  J Abnorm Psychol. 2015;124(2):256-265. doi:10.1037/abn0000028PubMedGoogle ScholarCrossref
36.
Wilcox  S, Evenson  KR, Aragaki  A, Wassertheil-Smoller  S, Mouton  CP, Loevinger  BL.  The effects of widowhood on physical and mental health, health behaviors, and health outcomes: the Women’s Health Initiative.  Health Psychol. 2003;22(5):513-522. doi:10.1037/0278-6133.22.5.513PubMedGoogle ScholarCrossref
37.
Reynolds  CF  III, Hoch  CC, Buysse  DJ,  et al.  Electroencephalographic sleep in spousal bereavement and bereavement-related depression of late life.  Biol Psychiatry. 1992;31(1):69-82. doi:10.1016/0006-3223(92)90007-MPubMedGoogle ScholarCrossref
38.
Pasternak  RE, Reynolds  CF  III, Hoch  CC,  et al.  Sleep in spousally bereaved elders with subsyndromal depressive symptoms.  Psychiatry Res. 1992;43(1):43-53. doi:10.1016/0165-1781(92)90140-XPubMedGoogle ScholarCrossref
39.
Buckley  T, Mihailidou  AS, Bartrop  R,  et al.  Haemodynamic changes during early bereavement: potential contribution to increased cardiovascular risk.  Heart Lung Circ. 2011;20(2):91-98. doi:10.1016/j.hlc.2010.10.073PubMedGoogle ScholarCrossref
40.
Irwin  M, Daniels  M, Risch  SC, Bloom  E, Weiner  H.  Plasma cortisol and natural killer cell activity during bereavement.  Biol Psychiatry. 1988;24(2):173-178. doi:10.1016/0006-3223(88)90272-7PubMedGoogle ScholarCrossref
41.
Buckley  T, Sunari  D, Marshall  A, Bartrop  R, McKinley  S, Tofler  G.  Physiological correlates of bereavement and the impact of bereavement interventions.  Dialogues Clin Neurosci. 2012;14(2):129-139.PubMedGoogle Scholar
42.
Buckley  T, Morel-Kopp  MC, Ward  C,  et al.  Inflammatory and thrombotic changes in early bereavement: a prospective evaluation.  Eur J Prev Cardiol. 2012;19(5):1145-1152. doi:10.1177/1741826711421686PubMedGoogle ScholarCrossref
43.
Fagundes  CP, Brown  RL, Chen  MA,  et al.  Grief, depressive symptoms, and inflammation in the spousally bereaved.  Psychoneuroendocrinology. 2019;100:190-197. doi:10.1016/j.psyneuen.2018.10.006PubMedGoogle ScholarCrossref
44.
Gerra  G, Monti  D, Panerai  AE,  et al.  Long-term immune-endocrine effects of bereavement: relationships with anxiety levels and mood.  Psychiatry Res. 2003;121(2):145-158. doi:10.1016/S0165-1781(03)00255-5PubMedGoogle ScholarCrossref
45.
Carey  IM, Shah  SM, DeWilde  S, Harris  T, Victor  CR, Cook  DG.  Increased risk of acute cardiovascular events after partner bereavement: a matched cohort study.  JAMA Intern Med. 2014;174(4):598-605. doi:10.1001/jamainternmed.2013.14558PubMedGoogle ScholarCrossref
46.
Stroebe  M, Schut  H, Stroebe  W.  Health outcomes of bereavement.  Lancet. 2007;370(9603):1960-1973. doi:10.1016/S0140-6736(07)61816-9PubMedGoogle ScholarCrossref
47.
Bae  JB, Kim  YJ, Han  JW,  et al.  Incidence of and risk factors for Alzheimer’s disease and mild cognitive impairment in Korean elderly.  Dement Geriatr Cogn Disord. 2015;39(1-2):105-115. doi:10.1159/000366555PubMedGoogle ScholarCrossref
48.
Sundström  A, Westerlund  O, Mousavi-Nasab  H, Adolfsson  R, Nilsson  LG.  The relationship between marital and parental status and the risk of dementia.  Int Psychogeriatr. 2014;26(5):749-757. doi:10.1017/S1041610213002652PubMedGoogle ScholarCrossref
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    1 Comment for this article
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    RE: Associations of widowhood and β-amyloid with cognitive decline in cognitively unimpaired older adults
    Tomoyuki Kawada, MD | Nippon Medical School
    I have read the article by Biddle et al. (1) with great interest. The authors conducted a prospective study to determine the effect of widowhood status on the level of brain β-amyloid and cognitive decline in 257 participants. The authors concluded that being widowed was significantly associated with accelerated β-amyloid-related cognitive decline during 3 years. Namely, the rate of cognitive decline among widowed participants with high β-amyloid was nearly 3 times faster than among married participants with high β-amyloid, presenting standardized regression coefficients (95% confidence intervals [CIs]) of -0.33 (-0.46 to -0.19) and -0.12 (-0.18 to -0.01), respectively. I have a concern about their study with special reference to sex difference, because percentage of widowed women occupied 88.6% of all widowed participants (n=35).

    I previously conducted a cross-sectional study to determine whether marital status is an independent risk factor for poor self-rated health (2). Adjusted odds ratios (ORs) (95% CI) of being male, having disease, physical complaints, depressive state, having lower levels of education, and being divorced for poor self-rated health were 1.41 (1.18–1.69), 10.8 (8.62–13.7), 1.11 (1.09–1.12), 1.11 (1.08–1.13), 1.22 (1.02–1.46), and 1.53 (1.01–2.31), respectively. I presented that health status was affected especially in male divorced inhabitants, and sex difference regarding health risk should be specified by further prospective studies.

    Regarding sex difference, Cuijpers et al. (3) conducted a meta-analysis of prospective studies regarding the effect of depression on mortality, stratified by sex. Among people with depression, relative risk (RR) (95% confidence interval [CI]) of men against women for mortality was 1.97 (1.63-2.37). In addition, RRs (95% CIs) of depression for mortality in women and in men were 1.55 (1.32-1.82) and 2.04 (1.76-2.37), respectively. Trevisan e al. also conducted a prospective study to examine the association between marital status and the incidence of frailty (4). Adjusted ORs (95% CIs) of men who had never married and were widowed against married men for developing frailty were 3.84 (2.76-5.35) and 1.43 (1.06-1.95), respectively. In contrast, adjusted OR (95% CI) of widowed women against married women for developing frailty was 0.77 (0.66-0.91).

    Although the mechanism of sex difference cannot be specified, frailty is a predictor of cognitive impairment and depression (5,6). Poor self-rated health is closely related to multi-morbidity, unhealthy behaviors and frailty (7), and risk factors for the progression of cognitive decline and increased level of brain β-amyloid should be evaluated by considering sex difference.


    References

    1. Biddle KD, Jacobs HIL, d'Oleire Uquillas F, et al. JAMA Netw Open 2020;3(2):e200121. doi:10.1001/jamanetworkopen.2020.0121

    2. Kawada T, Suzuki S. J Divorce Remarriage 2011;52(1):48-54.

    3. Cuijpers P, Vogelzangs N, Twisk J, et al. J Affect Disord 2014;161:47-54. doi:10.1016/j.jad.2014.03.003

    4. Trevisan C, Veronese N, Maggi S, et al. J Womens Health (Larchmt) 2016;25(6):630-637. doi:10.1089/jwh.2015.5592

    5. Chu NM, Bandeen-Roche K, Tian J, et al. J Gerontol A Biol Sci Med Sci 2019;74(11):1761-1770. doi:10.1093/gerona/glz134

    6. Brown PJ, Roose SP, O'Boyle KR, et al. Am J Geriatr Psychiatry 2020;28(2):145-154. doi:10.1016/j.jagp.2019.10.005

    7. Feenstra M, van Munster BC, MacNeil Vroomen JL, et al. BMJ Open 2020;10(2):e035012. doi:10.1136/bmjopen-2019-035012
    CONFLICT OF INTEREST: None Reported
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    Original Investigation
    Geriatrics
    February 26, 2020

    Associations of Widowhood and β-Amyloid With Cognitive Decline in Cognitively Unimpaired Older Adults

    Author Affiliations
    • 1Division of Geriatric Psychiatry, Department of Psychiatry, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
    • 2School for Mental Health and Neuroscience, Alzheimer Centre, Limburg, Maastricht University, Maastricht, the Netherlands
    • 3Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston
    • 4Princeton Neuroscience Institute, Princeton, New Jersey
    • 5Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston
    • 6Department of Neurology, Brigham and Women’s Hospital, Boston, Massachusetts
    • 7Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston
    JAMA Netw Open. 2020;3(2):e200121. doi:10.1001/jamanetworkopen.2020.0121
    Key Points español 中文 (chinese)

    Question  Is widowhood a specific risk factor associated with more rapid cognitive decline among cognitively unimpaired older adults with higher levels of brain β-amyloid, the Alzheimer disease biomarker?

    Findings  In this cohort study of 257 community-dwelling cognitively unimpaired older adults, widowhood and β-amyloid were additively and interactively associated with cognitive decline. These results were independent of demographic factors, cardiovascular disease risk, depression, health-related behaviors, and social support factors.

    Meaning  These findings suggest that widowhood may be an understudied risk factor for cognitive decline associated with Alzheimer disease and highlight the need for increased research and clinical attention to this high-risk group.

    Abstract

    Importance  To reduce the rising incidence of clinical impairment due to Alzheimer disease, it is essential to define older adults at highest risk. Widowhood may be an unrecognized factor contributing to accelerated clinical progression along the Alzheimer disease pathway among cognitively unimpaired older adults.

    Objective  To determine whether widowhood status and level of brain β-amyloid (ie, the Alzheimer disease pathologic protein) are additively or interactively associated with cognitive decline among cognitively unimpaired older adults.

    Design, Setting, and Participants  In this cohort study, 257 married, widowed, and unmarried (ie, never married, divorced, or separated) participants from the Harvard Aging Brain Study longitudinal cohort underwent baseline evaluation of neocortical β-amyloid levels using Pittsburgh compound B positron emission tomography and 4 annual cognitive assessments. Data were collected from September 2010 to February 2017 and analyzed from July 2018 to July 2019.

    Main Outcomes and Measures  Cognitive performance was measured using the Preclinical Alzheimer Cognitive Composite.

    Results  Of the 257 participants, 153 (59.5%) were women, and the mean (SD) age was 73.5 (6.1) years; 145 participants (56.4%) were married (66 [45.5%] women), 77 (30.0%) were unmarried (56 [72.7%] women), and 35 (13.6%) were widowed (31 [88.6%] women). Compared with married participants, widowed participants demonstrated worsening cognitive performance after adjusting for age, sex, socioeconomic status, depression, and β-amyloid levels (β = −0.11; 95% CI, −0.19 to −0.04; P = .002) with no difference observed between married and unmarried participants. Furthermore, widowed participants with higher baseline β-amyloid levels exhibited steeper cognitive decline (β = −0.22; 95% CI, −0.42 to −0.03; P = .02), indicating both independent and interactive associations of β-amyloid levels and widowhood with cognition. In a secondary model using dichotomous β-amyloid–marital status groupings, the rate of cognitive decline among widowed participants with high β-amyloid was nearly 3 times faster than among married participants with high β-amyloid (widowed, high β-amyloid: β, −0.33; 95% CI, −0.46 to −0.19; P < .001; married, high β-amyloid: β, −0.12; 95% CI, −0.18 to −0.01; P < .001).

    Conclusions and Relevance  In a sample of cognitively unimpaired older adults, being widowed was associated with accelerated β-amyloid–related cognitive decline during 3 years. Cognitively unimpaired, widowed older adults were particularly susceptible to Alzheimer disease clinical progression, emphasizing the need for increased research attention and evidenced-based interventions for this high-risk group.

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