The Loss when Losing a Loved One. (PDF)

The Loss when Losing a Loved One. Epidemiological studies of prolonged grief disorder. Heidi Saavedra Pérez  The work described in this thesis was performed within the framework of the Rotterdam Study at the Department of Epidemiology of the Erasmus Medical Center, Rotterdam, the Netherlands. The contribution of the study participants, the staff from the Rotterdam Study and all general practitioners and pharmacists is gratefully acknowledged. The Rotterdam Study is funded by Erasmus MC and Erasmus University Rotterdam; the Netherlands Organization for Health Research and Development, the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam Financial support for the publication was kindly provided by the Department of Epidemiology, Erasmus Medical Center and Erasmus University Rotterdam. Cover image: Eileen Campuzano Layout: Conejo de Colores Printing: ISBN: © Heidi Saavedra Pérez, 2018. For all published articles, the copyright has been transferred to the respective publisher.  The loss when Losing a Loved one. Epidemiological studies of prolonged grief disorder. Het verlies bij het verliezen van een geliefde. Epidemiologische studies van langdurige rouwstoornis. Proefschrift ter verkrijging van de graad van doctor aan de Erasmus Universiteit Rotterdam op gezag van de rector magnificus Prof.dr. R.C.M.E Engels en volgens besluit van het College voor Promoties. De openbare verdediging zal plaatsvinden op dinsdag 12 februari 2019 om 15.30 uur Heidi Saavedra Pérez geboren te Panamá, Panamá.  PROMOTIECOMMISSIE: Promotoren: Prof.dr. M.A. Ikram Prof.dr.H.W. Tiemeier Overige leden: Prof.dr Myriam Hunink Prof.dr. Paul Boelen Prof.dr Francesco Mattace Raso  Introduction. Cognition, structural brain changes and complicated grief. A population-based study. Prolonged Grief and Cognitive Decline: A Prospective Population-Based Study in Middle-Aged and Older Persons. The Longitudinal and Cross-Sectional Associations of Grief and Complicated Grief with Sleep Quality in Older Adults. The Impact of complicated grief on diurnal cortisol levels two years after loss: A population-based study. Silent brain infarcts: A cause of depression in the elderly? Markers of cerebral small vessel disease and severity of depression in the general population. Discussion Summary PhD portfolio List of publications About the author Acknowledgements 9 17 41 63 83 105 115 133 153 159 CONTENTS: Chapter 1. Chapter 2. Chapter 3. Chapter 4. Chapter 5. Chapter 6. Chapter 7. Chapter 8. Chapter 9. Chapter 10.     9 CHAPTER 1 Introduction  10  11 The most common serious adverse life event is the experience of the death of a significant person. Grief is the most usual reaction to such a loss, and is considered a normal and natural, albeit difficult, transition (1). Grief as a topic of study emerged in 20th century. Freud (1917), in his paper on mourning and melancholia attempted to differentiate the normal process of mourning from melancholia. Despite their similarities, Freud states, there are some fundamental differences: mourning is recognized as a healthy and normal process that is necessary for the recovery of the loss and would not be seen as pathology nor a need for medical intervention. However, melancholia is pathological condition, and a dangerous illness due to its poor prognosis and the common suicidal tendency (2). Though loss is an event that most people INTRODUCTION will encounter multiple times in their lives, it also can be a severely stressing experience. Although grief usually resolves within a delimited period, it may still have negative consequences for the health of a person: the exacerbation of preexisting levels of depression (3), increased risk of suicide (4), anxiety disorders (5), and decline in cognitive functioning (6-9), physical health problems, and higher rates of disability, use of medication and hospitalization (10) have all been associated with grief. Moreover, about 9-20% of the persons cannot deal with the loss and show symptoms of complicated and unresolved grief, termed prolonged grief disorder (PGD) (11). The prevalence varies with age, social, cultural and clinical background (12, 13). We can remember the famous queen of Castile, named Joanna the Mad, who could not cope with the death of her husband Philip the  12 Chapter 1 Handsome, and during 8 months, she remained with her husband’s coffin in a funeral procession that awoke awe and fear in the population. PGD includes a set of symptoms of separation distress, such as yearning for the deceased or intense feelings of loneliness; and traumatic distress, such as feelings of disbelief or that life is empty, being emotionally numb or troubled accepting the death, or bitterness. The symptoms are prominent, remain elevated at 6 months and beyond after the loss to the point of functional impairment, and are often resistant to antidepressant treatment (14, 15). PGD strongly affects the wellbeing of the person and has a great impact on the quality of life (16, 17). PGD has been associated with sleep disturbances (18), depression and a higher risk of suicide (19), and poor health (20). The impact of PGD on the cognitive functioning of adults and elderly persons is less known. This PhD thesis is divided into 8 chapters: Chapter 2 explores PGD, cognition and brain volumes. Chapter 3 focuses on PGD and cognitive decline. Chapter 4 explores PGD and sleep quality. Chapter 5 focuses on PGD and cortisol levels. Chapter 6 presents the research on the relation of silent brain infarcts with depression in the elderly. Chapter 7 presents markers of cerebral small vessel disease with severity of depression in the general population. Finally, in chapter 8, I discuss the main findings of this thesis. Cognition and Prolonged grief disorder From the earliest clinical descriptions of grief, researchers have noted that individuals with PGD have greater neurocognitive deficits compared to persons with normal grief and persons without grief (21). Several studies investigated the relation of (acute) grief with cognitive impairment, showing memory decline (immediate and delayed recall) in participants with grief (22,23); and worse performance in tests of attention (24). Recently, a descriptive study examined global and domain-specific cognitive functioning in individuals with PGD using the Montreal test. They found that participants had lower total Montreal scores, and visuospatial and attention scores relative to control participants (25). Yet, the relation between PGD remains a gap in the literature. Despite the absence of longitudinal studies of PGD and cognition, several explanations of the potential impact on cognitive decline have been put forward: Persons, who lose a loved one, show  13 Introduction sensory-perceptual alterations that have been associated with hallucinations and delusions. These deficits are more common in persons with PGD than in those without PGD (25% and 2%, respectively) (26). Equally, the attention of persons with PGD is usually directed toward aspects of the environment associated with the deceased (27). These findings suggest that persons with PGD may exhibit attentional bias or impairment in their interpretation of information of their external environment (28). They also exhibit a grief-related avoidance behavior (29), which is positively associated with overall PGD symptom severity (30). However, the temporal relation between PGD and cognition has not been determined; also, whether cognitive function in persons with PGD declines over the time has not been studied. We cannot rule out reverse causality; that is that cognitive problems precede the onset of grief and are related to its persistence. The underlying hypothesis for my thesis is that poor cognitive performance in persons with PGD relates with brain structural changes and the cognitive decline could be a symptom of the onset of a mild cognitive impairment. The aim of this thesis was to examine the relationship of PGD with different domains of cognition, and with brain volumes assessed by MRI in the general population. We also compared the cognitive decline prospectively through 7 years. Sleep and Prolonged grief disorder When a loved one dies, the majority of bereaved persons develops sleep problems, and this has been a frequent topic of study (31). Being widowed or without a partner has been associated with lower sleep quality (32). Few studies have study the prospective association between PGD and quality sleep, showing an overall poor sleep quality (33) The aim of this chapter was to examine the relationship between the sleep qualities and sleep duration in persons with normal grief and PGD, and a non- grieving reference group. The hypothalamic-pituitary-adrenal axis and Prolonged grief disorder Under conditions of stress, the hypothalamic-pituitary-adrenocortical (HPA) axis is stimulated and activates the secretion of cortisol into the bloodstream. An acute psychosocial stress like losing a loved one is typically accompanied by increased secretion of cortisol, as an adaptation to the stressor and then a return to normal levels; but it is the chronic dysregulation of cortisol that is  14 Chapter 1 implicated in a host of psychological and physical health conditions (34). Previous studies of grief and cortisol showed more dysregulation on cortisol patterns and an increased mortality risk of the bereaved person (35,36). These few previous studies showed conflicting and controversial results, in one study a flatter slope across the day was observed in persons with PGD, but in another study the occurrence of a flatter slope in persons with grief was independent of the symptoms of PGD (37,38). In this chapter, we aimed to examine the association of morning cortisol and summary cortisol measures, e.g. the slope and the morning rise, with grief and PGD. Silent brain infarcts and depression Alexopoulus introduced the term of vascular depression in 1997, and presenting this hypothesis he postulated that cerebral small vessel diseases can cause or exacerbate depression in elderly people (39). Krishnan proposed the same concept focusing on vascular lesions such as white matter lesions (WMLs) using magneting resonance imaging (MRI) methods (40). In this chapter, we aimed to test the association of non-clinical cerebral small vessel disease with depression longitudinally in general population. Study Setting The analyses performed in this thesis were based on data from Rotterdam Study, a large population based prospective cohort among adults aged 55 or over living in the Ommoord district in the city of Rotterdam in The Netherlands (78 % of 10,215 invitees) (21). In the Rotterdam Study, the measurement of PGD is through the Inventory of Complicated Grief (ICG), which was introduced in the fourth follow-up examination (2002-2004) of the original cohort and in the second follow-up examination of the additional cohort (2004-2005). All data for this study were collected during an interview at the participant’s home. (41).  15 Introduction Rozenzweig A, Prigerson, H, Miller, MD, Reynolds, CF 3rd. Bereavement and late-life depression: grief and its complications in the elderly. Annu Rev Med 1997; 48: 421-8. Freud (1917). Mourning and Melancholia. The Standard Edition of the Complete Psychological Works of Sigmund Freud, XIV (1914-1916): On the History of the PsychoAnalytic Movement, Papers on Metapsychology and Other Works (pp. 237-258). Gilewski MJ, Farberow NL, Gallagher DE, et al: Interaction of depression and bereavement on mental health in the elderly. Psychol Aging 1991;6:67-75. Erlangsen A, Jeune B, Bille-Brahe U, et al: Loss of partner and suicide risks among oldest old: a population- based register study. Age Ageing 2004;33:378-83. Shear MK, Skritskaya NA. Bereavement and anxiety. Curr Psychiatry Rep. 2012 Jun;14(3):169-75. doi: 10.1007/s11920-012-0270-2. Aartsen MJ, Van Tilburg T, Smits CH, et al: Does widowhood affect memory performance of older persons? Psychol Med 2005;35:217-26. Corruble E, Falissard B, Gorwood P: DSM bereavement exclusion for major depression and objective cognitive impairment. J Affect Disord 2011;130:113-7. Rosnick CB, Small BJ, Burton AM: The effect of spousal bereavement on cognitive functioning in a sample of older adults. Neuropsychol Dev Cogn B Aging Neuropsychol Cogn 2010;17:257-69. Ward L, Mathias JL, Hitchings SE: Relationships between bereavement and cognitive functioning in older adults. Gerontology 2007;53:362-72. Stroebe M, Schut H, Stroebe W: Health outcomes of bereavement. Lancet, 2007;370:1960-73. 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