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Spousal_Dementia_Car..
Spousal_Dementia_Car..
Spousal_Dementia_Car..
Spousal_Dementia_Car..
Spousal_Dementia_Car..
Spousal_Dementia_Car..
Spousal_Dementia_Car..
Spousal_Dementia_Car..
Spousal_Dementia_Car..
Spousal_Dementia_Car..
Spousal_Dementia_Car..
Spousal_Dementia_Car..
Spousal_Dementia_Car..
Spousal_Dementia_Car..
Spousal_Dementia_Car..
Spousal_Dementia_Car..
Spousal_Dementia_Car..
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  • 1. Incident dementia risk among spouse dementia caregivers Incident Dementia Risk Among Spousal Dementia Caregivers: The Cache County Study. Maria C. Norton, Ken R. Smith, Truls Østbye, JoAnn T. Tschanz, Chris Corcoran, Sarah Schwartz, Kathleen W. Piercy, Peter V. Rabins, David C. Steffens, Ingmar Skoog, John C. S. Breitner, Kathleen A. Welsh-Bohmer For the Cache County Investigators From the Department of Family Consumer and Human Development, Utah State University (Drs. Norton & Piercy); the Department of Family and Consumer Studies and the Huntsman Cancer Institute, University of Utah (Dr. Smith); the Department of Community and Family Medicine, Duke University Medical Center (Dr. Østbye); the Department of Psychology, Utah State University (Drs. Norton & Tschanz), the Department of Mathematics and Statistics, Utah State University (Dr. Corcoran and Ms. Schwartz); Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine (Dr. Rabins), the Department of Psychiatry and Behavioral Sciences, Duke University Medical Center (Dr. Steffens); VA Puget Sound Health Care System and Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle (Dr. Breitner); the Joseph and Kathleen Bryan Alzheimer’s Disease Research Center, Duke University (Drs. Østbye & Welsh-Bohmer). Address correspondence to: Dr. Maria Norton, Cache County Memory Study, Utah State University, 4440 Old Main Hill, Logan, UT 84322-4440; Phone: 435-797-1599; Email address maria.norton@usu.edu; Fax: 435-797-2771 Word Count: 4,556 Portions of this paper were presented at the International Conference on Alzheimer’s Disease in Vienna, Austria, July 11-16, 2009. This work was supported by NIH grants: AG-031272, AG-011380, and AG-021136 1
  • 2. Incident dementia risk among spouse dementia caregivers Abstract Chronic psychosocial stressors can increase risk in caregivers for adverse health outcomes including depression, anxiety, and cognitive decline. Few studies have examined the long-term effects on incident dementia risk of spousal dementia caregiving. In a population-based sample of 2,442 subjects (1,221 married couples) aged 65 and older, we tested the hypothesis that spousal dementia caregiving is associated with increased risk for incident dementia in the caregiver. Incident dementia was diagnosed in 255 subjects Cox proportional hazards regression tested the effect of time-dependent exposure to dementia caregiving adjusted for age, gender, APOE genotype, and (to control for shared socioeconomic status that may impact shared dementia risk) husband’s education and occupation. A subject (i.e.caregiver) whose spouse experienced incident dementia onset had a six-fold (HR=6.01, 95% CI: 2.23-16.17, p=.0004) increase in the hazard for incident dementia in relation to subjects whose spouses were dementia free. In gender-stratified analyses, husband caregivers were at even higher risk (HR=11.93, 95%CI: 1.67-85.52, p=.0136), compared to wife caregivers (HR=3.66, 95%CI: 1.15-11.61, p=.0277). These results suggest that the chronic and often severe stress associated with dementia caregiving exerts substantial risk for the development of dementia in spouse caregivers, with relative effects greater for husband caregivers. 2
  • 3. Incident dementia risk among spouse dementia caregivers Introduction Informal (unpaid) dementia caregiving is a difficult job involving great demands on the caregiver’s time and energy, with typically great physical demands in providing personal and instrumental assistance to the spouse with dementia (the care recipient). The caregiver burden often seems to be a cycle repeated every 24 hours which, to many caregivers, may seem like a “36 hour day” (Mace & Rabins, 2006). A feeling of loss of personal control or loss of individual self has also been associated with dementia caregiving (Boss, 1990). A growing body of research on dementia caregiving has demonstrated higher rates of depression (Bergman-Evan, 1994; Schulz et al, 1990; Pinquart & Sorensen, 2003; Sörensen et al, 2006), other physical health problems (Vitaliano, et al, 2003) and greater mortality (Christakis & Allison, 2006; Schulz & Beach, 1999) among caregivers. This may be especially true for spouse caregivers who are of the same age as, or even older than, the person with dementia, with the role of full-time caregiver potentially jeopardizing their own health. While spousal dementia caregivers may report a variety of positive aspects to their caregiving role (Bacon et al, 2009), the unique and extreme challenges of caregiving may result in physical and mental exhaustion, feelings of anxiety, loneliness and hopelessness. While providing care to an older person with physical impairments or other illnesses may also include many of these stressors, a study of over 1,500 caregiving households revealed that dementia caregivers provided more assistance, reported more personal sacrifices and reported that caregiving was more stressful, compared to caregivers of physically-impaired older adults (Ory, 1999). 3
  • 4. Incident dementia risk among spouse dementia caregivers While much has been published on the effect of caregiver stress on depression and cardiovascular health in the caregiver, very few studies have examined effects on the caregiver’s cognitive function and subsequent risk for dementia. A plausible biological mechanism has been suggested by McEwen and Sapolsky through maladaptive neuroendocrine response from chronic stress (McEwen; 2002; Sapolsky, Krey,& McEwen, 1986). An emerging literature showing associations between chronic stress from spousal caregiving and cognitive deficits in the caregivers supports this hypothesis. deVugt et al (2006) found that spouse dementia caregivers had significantly worse general cognitive functioning, speed of information processing and verbal memory, compared to age-, sex-, and education-matched controls. Another study found that caregivers of spouses with dementia performed more poorly on a digit symbol test of complex attention and cognitive speed (Caswell, et al, 2003). Results from the Nurses Health Study revealed that female caregivers of ill spouses performed worse than non-caregivers on a general cognitive screening test, and on a test of immediate and delayed recall of a 10-item word list (Lee, et al, 2004). Decline in vocabulary over a two-year period was significantly greater in caregivers of spouses with dementia than in matched controls (Vitaliano, et al, 2005). Finally, Mackenzie et al (2007) demonstrated that caregivers of relatives in palliative care exhibited significant impairments in attention and had difficulty monitoring their performance and regulating attentional resources, compared to a control sample. While these few studies show consistent evidence that the stress associated with spousal dementia caregiving may lead to declines in cognitive function for the caregiver, all studies were limited by small sample sizes. Importantly, no study included longitudinal follow-up of caregivers combined with in-depth clinical assessment for dementia that confirms whether these observed cognitive impairments are transitory or may actually lead to dementia in the caregiver. 4
  • 5. Incident dementia risk among spouse dementia caregivers We report here results from a population-based study of dementia wherein 2,442 older married individuals participated in up to 12 years of longitudinal cognitive evaluation. An in- depth dementia ascertainment protocol was employed to diagnose dementia in both spouses. Dementia onset ages were determined for each spouse, facilitating time-dependent analyses of the effects of exposure to spousal dementia caregiving. We hypothesized that after onset of caregiving for dementia, the caregiver is subsequently at increased risk for incident dementia, due to the chronic stress associated with spousal dementia caregiving. Further, because of the higher rates of incident dementia (Miech et al, 2002) and depression (Luijendijk et al, 2008) among women, and the greater tendency among women caregivers to report poorer well-being as a function of caregiver burden (Croog, et al, 2001), we hypothesized that the effect of spousal dementia caregiving on subsequent dementia in the caregiver would be stronger for wives caring for husbands with dementia, than for husbands caring for wives with dementia. Subjects The Cache County Study on Memory Health and Aging (CCMS) is an on-going investigation of aging in general, and dementia and cognitive impairment in particular, among the elderly population of Cache County, Utah. In 1995 we invited all elderly (age 65 or older) individuals who were permanent residents of Cache County to participate in the first wave of our study. There were 5,092 participants at the baseline interview in the CCMS, i.e. 90% of all eligible residents of Cache County. In this cohort, 3299 were married, 1534 were widowed, 167 were divorced or separated, 82 had never married, and 10 had missing marital status, as of the baseline interview. Of those who were married, 2,738 had a spouse who was also a CCMS participant. After removing from this sample 296 subjects with prevalent dementia, the final analysis sample for the present study included 2,442 participants, i.e. 1,221 married couples. 5
  • 6. Incident dementia risk among spouse dementia caregivers Each of these 2,442 participants serves as both the index subject whose incident dementia is being modeled, as well as the spouse whose dementia diagnosis (or lack thereof) is used to generate the exposure variable for each index subject. Of the 2442 observed participants, 229 were “exposed to” a spouse diagnosed with dementia and thereby to spousal dementia caregiving. These subjects with known exposure were observed an average of 9.22 (SD =3.05) years. This time includes observation time before (M = 5.09, SD = 3.20 years) and after (M = 4.14, SD = 3.15 years) spouse’s dementia onset. The remaining 2213 subjects who were never exposed to a spouse diagnosed with dementia were followed for a slightly longer period, on average (M = 4.45, SD = 4.24 years). Dementia Ascertainment Clinical Evaluation The CCMS utilized a multi-stage dementia ascertainment protocol described elsewhere (Breitner et al, 1999), which was repeated in four successive triennial waves (1995-7, 1998- 2000, 2002-4, and 2005-7). Briefly, within each wave, screening began with an in-person interview that included an adaptation (Tschanz et al, 2002) of the modified Mini-Mental State examination (3MS; Teng & Chui, 1987) or, for those unable to participate, the Informant Questionnaire for Cognitive Disorder in the Elderly (IQCODE; Jorm & Jacomb, 1989) administered to a collateral informant. Participants who screened positive for possible dementia then completed an in-depth clinical assessment (CA), as did a 19% sub-sample of “designated controls” who completed a CA in each wave. Specially trained nurses and psychometric technicians administered the CA, which included a brief physical evaluation, a detailed history of medical and cognitive symptoms, a structured neurological examination, and a one-hour battery of neuropsychological tests. 6
  • 7. Incident dementia risk among spouse dementia caregivers A geriatric psychiatrist and neuropsychologist reviewed these data and assigned working diagnoses of dementia (DSM-III-R; 1987) or other cognitive syndromes. Subjects with a working diagnosis of dementia were then selected for geriatric psychiatric examinations and laboratory studies including neuroimaging. To substantiate or refine their diagnoses, these individuals were re-examined 18 months after their initial CA. A multidisciplinary consensus panel of experts in neurology, geriatric psychiatry, neuropsychology, and cognitive neuroscience reviewed all available data and assigned final consensus diagnoses. Onset was defined as the year in which a participant unambiguously met DSM-III-R criteria for dementia. Imputation of Incident Dementia for Subjects with Incomplete Ascertainment Incomplete ascertainment was identified in 253 subjects who screened positive for dementia but failed to complete the CA (due to death, refusal or moving out of area between screening and CA). Four possible methods for addressing this scenario were considered. One approach would be to assume that 100% of all such individuals had dementia at the point of the screen positive result, while a second approach would assume that none of these individuals ever had dementia. A third approach would discard all observation years between the prior wave (where subject received a non-dementia diagnosis) to the point of the incomplete ascertainment with the screen positive result, an option that would discard 1,092 person-years of observation. A fourth approach (believed to get closest to “truth”) would be to impute dementia onset by utilization of all available screening data, employing conservative diagnostic criteria for dementia. It is this fourth approach that was used in the present study, where screening data were used to infer dementia status for those with incomplete ascertainment at their last wave of participation. [Note: We also ran models using the third approach (defining right censoring as of preceding wave with non-dementia diagnosis, i.e. no imputation) but as results were comparable, 7
  • 8. Incident dementia risk among spouse dementia caregivers we report herein only the models using the imputation approach which resulted in preservation of all person-years of observation.]. In Waves 1 and 2, individuals who were screen-positive on either the 3MS or IQCODE were asked to undergo further evaluation with the Dementia Questionnaire (DQ), a semi- structured informant interview designed to inventory cognitive or functional difficulties and medical conditions relevant to dementia (Kawas, et al, 1994). The DQ interviews were rated by a study neuropsychologist who estimated degree of cognitive impairment as 1=cognitively normal, 2=mild cognitive impairment, 3=moderate cognitive impairment, 4=severe cognitive impairment, or 5=dementia. Among subjects with “incomplete ascertainment,” where a DQ rating was available (Waves 1 and 2), it was used, with dementia imputed if DQ rating = 5, and non-dementia was imputed if DQ rating <5. When no DQ was available in Waves 1-4, data from the first screening stage were used, with conservative cut-points. If the IQCODE score was >= 3.6 (Se=.80, and Sp=.82; Jorm, 2004) or if the 3MS was below an age/gender/education-specific cut-off score (Se=1.00-.61, Sp=.83-.94 for age groups 65-69, 70-74, 75-79, 80-84, 85-89, 90+ years, respectively; Tschanz, et al, 2002), dementia was imputed, and non-dementia was imputed otherwise. Whenever dementia was imputed with DQ rating, 3MS, or IQCODE data, the onset age was imputed to be the mid-point between the last wave of complete (non-dementia) evaluation and the wave with incomplete ascertainment. This strategy “recouped” 1,092 lost person-years of observation that would otherwise have resulted in shorter observation periods for subject or spouse (or both). Covariates 8
  • 9. Incident dementia risk among spouse dementia caregivers Subject’s gender and age (in years) at baseline interview were included as covariates. Additionally, at baseline interview, we obtained buccal DNA from consenting participants (97%) for determination of genotype at APOE. Following the method of Richards and colleagues (1993) APOE genotypes were determined using polymerase chain reaction (PCR) amplification and a restriction isotyping method described by Saunders and colleagues (1993). To adjust for shared environmental exposures that might increase risk for dementia in both spouses, and thereby be confounded with the effect of spousal dementia caregiving, we adjusted for socioeconomic status (SES), a significant predictor of many health outcomes including dementia (Fotenos et al, 2008; Goldbourt et al, 2007). SES was measured with husband’s education and occupation, given that these are much stronger predictors of couple- level socioeconomic status, on average in this cohort, than wife’s education and occupation. Husband’s education was recorded in years. Following the Dictionary of Occupational Titles (U. S. Department of Labor, 1991), husband’s occupation of longest duration was coded into nominal categories of (1) professional, technical, managerial; (2) clerical and sales; (3) service; (4) agricultural; (5) processing; (6) machine trades; (7) bench work; (8) structural work, and (9) miscellaneous. Given the very low frequencies of categories 5-9, these were combined into one group, labeled hereafter as “machine/misc.” Data Analysis A series of Cox proportional hazards regression models were computed to test for the association between spouse dementia caregiving, a time-varying covariate, and subsequent risk for incident dementia in the caregiver, before and after adjustment for covariates (Cox & Oakes, 9
  • 10. Incident dementia risk among spouse dementia caregivers 1984). Using expert consensus diagnoses and the imputation protocol described above, each of the 2,442 subjects was identified as being either an incident dementia case (with corresponding age of onset—to the nearest integer year), or was considered “right censored” at the last completed visit. Cox models were fit, stratified by baseline age group (<75, 75-85, 85+ years), which allows each stratum to have its own baseline hazard rate. Thus, the parameter estimate for “age” in the model actually reflects the general effect of each additional year of age as applied to a given age stratum (Cox & Oakes, 1984). Observation Time. For purposes of modeling time to incident dementia, each subject’s observation time started at their own baseline screening visit and ended at 1) their own dementia onset, 2) their own right-censoring, or 3) their spouse’s right-censoring (death or loss to follow-up), whichever took place first. When spouse’s right-censoring date occurred first, the decision to end subject’s observation at this earlier date was a conservative but necessary approach due to unknown exposure to dementia caregiving from the point of spouse’s right-censoring forward. Thus, spouse dementia onset (i.e. subject’s exposure to dementia caregiving) was ignored if it occurred after subject’s dementia onset, and subject’s dementia onset was ignored if it occurred after spouse’s right-censoring (due to unknown exposure status from this point forward). Dementia Caregiving Exposure Time. Although many caregiving activities likely commenced previously, for analyses reported here, exposure to spousal dementia caregiving was presumed to commence at the spouse’s dementia diagnosis. In epidemiological studies generally, risk factors can have long-lasting residual effects after initial exposure (e.g. development of AIDS after exposure to the HIV 10
  • 11. Incident dementia risk among spouse dementia caregivers virus), or alternatively, risk may return to normal or near-normal levels after exposure has ended (e.g. risk for development of cancer after exposure to tobacco smoking). Recent studies demonstrate that caregivers experience continued deterioration of spatial working memory and delayed episodic memory, even after the death of the care recipient (Mackenzie et al, 2007). Such associations suggest long-term cumulative effects of psychosocial stress associated with dementia care-giving. Thus, in the present work, the approach of “once exposed, always exposed” was implemented with the exposure variable not being reset to “unexposed” after death of the spouse with dementia. Adjustments for Widowhood and Dependent Observations within Dyads The very small number of unexposed subjects (0 men, 4 women) experiencing widowhood over the entire period of observation time precluded our ability, but obviated the need, to adjust for the potential confounding effects of widowhood. It is possible that the association between the risks of dementia shared by spouses may not be the result of dementia caregiving of one spouse for another but rather because they are exposed to some common but unobserved factor. This possibility was considered by refitting the Cox proportional hazard models but with the inclusion of a shared frailty parameter that captures the potential influence of a shared risk among spouses. A shared frailty model is a random effects model where the frailties are common among spouses (Cleves, Gould, Gutierrez & Marchenko, 2008). Models that include a shared frailty generated results (not shown) were comparable to those reported here. Additionally, analyses were stratified by subject gender, to separately examine effects of 11
  • 12. Incident dementia risk among spouse dementia caregivers spousal dementia caregiving on husbands vs. wives (with such models not requiring the inclusion of the shared frailty parameter). Results In this community-based sample of 2,442 older adults (from 1,221 married couples), husband baseline age ranged from 65.7 to 100.1 (M=75.7, SD=5.9) years and wife baseline age ranged from 65.4 to 93.7 (M=73.1, SD=5.3) years. Length of marriage before baseline ranged from 1 to 73 years (M=48.9, SD=11.5). Only four couples divorced some time after baseline interview, with all other couples remaining married up to index subject’s dementia onset or right censoring, or up to right-censoring in spouse, whichever occurred first. Table 1 provides demographic summary statistics to describe the sample, along with statistical tests of bivariate relationships. Incident dementia was significantly associated with older age (p<.001), exposure to dementia caregiving (p=.022), and having one or two e4 alleles at APOE (p<.001). An initial proportional hazards regression model of survival time to incident dementia revealed a significant hazard ratio for exposure to spousal dementia caregiving (HR=6.399, 95%CI: 2.377-17.226, p=.0002). In the fully-adjusted model (Table 2), older age (p=.0123), one e4 allele (p=.0068) or two e4 alleles (p<.0001) (versus no e4 allele) at the APOE locus were associated with significantly higher risk of incident dementia, while higher SES (husband with professional/ technical/managerial occupation) was associated with significantly lower risk of incident dementia (p=.0183). In this same fully-adjusted model, exposure to spousal dementia caregiving was still associated with a six-fold increased risk for incident dementia (HR=6.01, 95%CI: 2.231-16.171, p=.0004). When analyses were stratified by gender of the index subject 12
  • 13. Incident dementia risk among spouse dementia caregivers (i.e. dementia caregiver), husband caregivers were at even higher risk (HR=11.93, 95%CI: 1.67- 85.52, p=.0136), compared to wife caregivers (HR=3.66, 95%CI: 1.15-11.61, p=.0277). Discussion To our knowledge, this is the first population-based study to examine risk for incident dementia among spouse caregivers of persons with dementia. We observed a striking six-fold increased risk for incident dementia among older adults exposed to spousal dementia caregiving, compared to married older adults whose spouse never developed dementia. This effect was robust after adjusting for age, gender, education and APOE genotype, all factors known to be associated with dementia risk. This effect also remained after further adjustment for socioeconomic status, a key indicator of shared environmental exposures, which, at least in part, ruled out confounding with common lifestyle factors that may lead to increased dementia risk in both spouses (e.g. diet, access to medical care). Serving as primary care provider to an individual with dementia is stressful regardless of age (Mace & Rabins, 2006), but the burden for spouse caregivers may be even greater due to their own advanced age, possible functional limitations, and greater likelihood of fatigue at physical exertion. As suggested by interdependence theory of dyadic relationships (Kelley & Thibaut, 1978), spouse caregivers, as with spouses or relationship partners generally, become interdependent over time through their interactions. As interdependence increases, so does concern for the partner’s outcomes, and a transformation of motives occurs from motives of self interest to pro-relationship motives (Lewis, McBride, Pollak, Puleo, Butterfield, & Emmons, 2006). However, cognitive and functional decline in the spouse with dementia forces caregivers to face the realization that, while there may be occasional “good days” and successes, the 13
  • 14. Incident dementia risk among spouse dementia caregivers progressive nature of dementia is relentless. Neuropsychiatric disturbances are particularly stressful and are the most common reason for institutionalization (Kalapatapu & Neugroschl, 2009). The caregiver must grieve not only the certainty of the spouse’s death in the near future leaving them with less time together, but must also grieve the loss of the pre-dementia relationship quality as the spouse with dementia experiences further declines as the disease advances. The caregiver may or may not have or take the opportunity for respite periodically to rejuvenate, but if this indulgence is permitted oneself, often there is guilt associated with the temporary delegation of caregiving duties to others (Albinsson & Strang, 2003). All of these factors impose great stress burdens on the spouse caregiver and those without strong support systems or who have more depressed or anxious tendencies are more likely to suffer the deleterious effects on the brain, increasing their own risk for dementia. Our findings provide evidence that the cognitive impairments demonstrated by other studies among spouse dementia caregivers (deVugt et al, 2006; Caswell, et al, 2003; Lee, et al, 2004; Vitaliano, et al, 2005; Mackenzie et al, 2007) are not always transient, and that there is a significant risk for the chronic stress of caregiving to result in dementia in the care provider. The magnitude of effect we observed was not borderline in clinical significance but was of substantial significance—a six-fold increase in risk overall, a finding that can be of vital importance for healthcare providers. Vigilance in monitoring the well-being and coping of the spouse dementia caregiver is recommended, while at the same time continuing to treat the person with dementia. Treatment for depression, stress management interventions, dementia educational seminars, and referrals to respite services are among the helps that healthcare providers can offer the spouse caregiver. Further, the caregiver’s health can directly affect the quality of care provided to care recipients, because preserving cognitive function in the caregiver 14
  • 15. Incident dementia risk among spouse dementia caregivers will ensure better attention to a host of factors such as personal hygiene, medication compliance, and engagement in cognitively stimulating activities for the care recipient. Thus, practitioners who treat a patient with dementia should also consider the dyad, and provide surveillance, diagnosis and treatment to two patients, not just one. Psychosocial stress is often associated with elevated levels of biomarkers of physiological stress reactivity. Chronic stress, especially in those with maladaptive coping strategies, may lead to a disregulation of the neuroendocrine response, ultimately resulting in neuronal damage and higher AD risk (McEwen, 2002; Sapolsky, Krey,& McEwen, 1986). A chronic stressor such as dementia caregiving may cause excessive activation of the HPA axis and high levels of glucocorticoids, resulting in cell death in regions of the hippocampus. This damage is hypothesized to diminish the normal inhibitory feedback of the HPA axis, resulting in ongoing activation of this system and higher glucocorticoid levels, termed the “glucocorticoid cascade hypothesis” advanced by Sapolsky et al (1986). This has been demonstrated in Alzheimer’s caregivers who had significantly higher interleukin-6 (but not C-reactive protein) levels than controls (von Känel, et al, 2006). Instrumental and emotional social supports may act as protective, moderating factors to enhance resilience in the face of high caregiver stress burden, however, access to such supports varies greatly (Wilks & Croom, 2008). In gender-stratified analyses, both husband and wife dementia caregivers were at significantly increased risk for incident dementia. However, the effect was even more pronounced for husband caregivers who experienced an almost 12-fold increased risk, while wives experienced an almost 4-fold increased risk. While this was contrary to our hypothesis, there are several possible explanations for this finding. Although many husbands make satisfactory adjustments to the dementia caregiver role, Calasanti and Bowen (2006) found that 15
  • 16. Incident dementia risk among spouse dementia caregivers caregiver husbands were more challenged than wives to adapt to the performance of daily care tasks, perhaps because dementia caregiving involves tasks with which husbands have been somewhat less familiar. In addition, husbands’ shrinking social networks and loss of meaningful civic and work activities may contribute to a profound sense of isolation (Kaye & Applegate, 1994; Russell, 2007). Such isolation may in turn contribute to increased stress levels and a sense of role captivity, the latter of which has been shown to lead to psychological distress in husband caregivers (Levesque, Ducharme, Zarit, Lachance, & Giroux, 2008). Despite such distress, male caregivers may be less likely than women caregivers to seek support for their feelings of isolation and captivity. Gottman and Carrère (1994) found that men are less likely than women to use their relationships with others to understand and process their emotions. Likewise, Julien, Arellano, and Turgeon (1997) reported that men are more likely than women to use diversion talk or activities as ways to cope with negative affect. It is also possible that the decline in marital interactions, shared meanings, and overall marital quality experienced by husband caregivers of wives with dementia (Wright, 1991; 1994) has a more deleterious impact on husbands because of the centrality of marriage in their support system. Relational deprivation, defined as the loss of closeness and former levels of communication in the marriage, is associated with higher levels of psychological distress for husband caregivers (Levesque et al). The loss of a primary support, coupled with greater reluctance to reach out to others for emotional support, may increase men’s risk of negative health outcomes. Finally, self-neglect is not uncommon among family caregivers (Ortiz, Lamdan, Johnson, & Korbage, 2009; Portnoy, 1993) and is associated with poorer physical functioning (Dong, 16
  • 17. Incident dementia risk among spouse dementia caregivers Mendes de Leon, & Evans, 2009). Men are at greater risk for cardiovascular health conditions (Eggers et al, 2008) and even when not in a caregiving role, are more likely to delay help seeking when they become ill (Galdas, Cheater, & Marshall, 2005), compared to women. Thus, husband caregivers may be at increased risk for incident dementia not only from effects of the psychosocial stress associated with caregiving, but also from their own neglected comorbid vascular conditions, which are in turn associated with increased risk for dementia (Hayden et al, 2006; Qiu, Ronchi, & Fratiglioni, 2007). A limitation of this study is that we did not have data on whether these subjects were providing non-dementia care to spouse or others. To the extent that subjects in the non-exposed group were actually experiencing chronic stress due to non-dementia caregiving, our results would be biased toward the null. However, given the strong effect observed for dementia caregiving, this concern is alleviated. Dementia caregiving was presumed to begin at the onset of dementia in the spouse and was not defined from direct questioning as to when caregiving duties actually began, as these data were not available. This is likely a conservative estimate of exposure to the demands of dementia caregiving, given that caregiving assistance and compensation for one’s spouse’s declining cognitive abilities likely begins much earlier than when clinical symptoms progress to unambiguously meet criteria for dementia. In a meta- analysis of 47 studies, Bäckman and colleagues (2005) suggested that preclinical changes can be detected for many years prior to AD onset, however, 3 years prior to dementia onset symptoms of prodromal AD are more reliably seen. Another limitation of this study was the lack of data on caregiver personality, cognitive appraisals of the caregiving experience, or perceived stress. These indicators of subjective stress are potentially important modifiers of the effect of chronic caregiver stress on risk for incident 17
  • 18. Incident dementia risk among spouse dementia caregivers dementia in the spouse caregiver. Further, no data were available on social supports, respite, or whether others shared caregiving duties with the spouse, or general coping strategies used by the spouse caregiver for dealing with stress generally. Our sample was also not large enough for us to study the effects of widowhood after commencement of spousal dementia caregiving. Additionally, while we were able to adjust for the effects of spousal dementia caregiving for socioeconomic status (husband’s education and occupation), this was an imperfect adjustment for the entire universe of shared environmental exposures common to both spouses. There may be residual confounding to the extent that couples may have been exposed to risk factors that increased risk for dementia in both spouses which were not entirely captured by socioeconomic status such as a shared active or sedentary lifestyle (Lensegrav-Benson et al, 2004) or shared habits as to use of neuroprotective agents such as antioxidant vitamin supplements or anti- inflammatory medications (Fotuhi et al, 2008). To the extent that this is true, the effect we see here may not be entirely due to cumulative damage due to chronic psychosocial stress in the caregiver. Finally, it should be noted that while the effect sizes are substantial, the confidence intervals are large, owing to the relatively small number of spouse pairs where both spouses received a dementia diagnosis. Although effect size estimates vary, all results reported here, whether in combined or stratified analyses, consistently suggest that the chronic stress and work of spouse dementia caregiving exerts deleterious effects on the caregiver’s own dementia risk. There remains a clear need for additional work to ascertain important mediators and moderators of the effect of spouse dementia caregiving on risk for dementia in the caregiver. Future studies of similar design with larger samples may be able to determine whether incident dementia risk in the spouse caregiver is reduced after widowhood or institutionalization of the spouse with dementia. More elaborate 18
  • 19. Incident dementia risk among spouse dementia caregivers analyses that examine the effect of the spouse’s rate of clinical dementia progression and behavioral disturbances may identify specific patterns that are more stressful to spouse caregivers, thereby helping to identify more vulnerable caregivers for interventions. Consideration of other psychosocial stressors that may compound the effects of dementia caregiving, whether concurrent or cumulative over the lifespan, will be important to pursue. Studies are also needed that will compare different coping strategies of caregivers, along with stress-related biomarkers, to determine which strategies result in less severe neuroendocrine reactivity and are thus generally more protective against dementia risk in the caregiver. These will help inform interventions that will not only help the caregiver maintain positive well-being during the caregiving experience, but may even help preserve cognitive function for their remaining years, after the work of caregiving is finished. 19
  • 20. Incident dementia risk among spouse dementia caregivers Table 1. Bivariate relationships between demographic variables and incident dementia Demographic Variable Subjects without Incident Dementia (n=2,187) Subjects with Incident Dementia (n=255) Bivariate tests: (independent samples t-test for continuous; chi- square test for categorical) Subject’s Age at baseline interview (M, SD) 74.2 (5.8) 75.9 (5.8) p < .001 Spouse’s Age at baseline interview (M, SD) 74.4 (5.7) 74.7 (6.2) p = .402 Husband’s education * in years (M, SD) 14.0 (3.4) 13.8 (3.3) p = .508 Exposure to spousal dementia caregiving (N, %) 195 (8.9%) 34 (13.3%) p=.022 Subject APOE: zero ε4 allele (N, %) 1482 (68.9%) 147 (57.9%) p < .001 Subject APOE: one ε4 allele (N, %) 625 (29.1%) 85 (33.5%) Subject APOE: two ε4 alleles (N, %) 43 (2.0%) 22 (8.7%) Husband Occupation *: Professional, technical, management (N, %) 938 (42.9%) 100 (39.2%) p=.703 Husband Occupation: Clerical, sales (N, %) 178 (8.1%) 20 (7.8%) Husband Occupation: Service (N, %) 61 (2.8%) 9 (3.5%) Husband Occupation: Agriculture (N, %) 457 (20.9%) 61 (23.9%) Husband Occupation: Machine/ miscellaneous (N, %) 553 (25.3%) 65 (25.5%) * Husband’s education (and occupation) refers to subject’s own, if male, and spouse’s, if female 20
  • 21. Incident dementia risk among spouse dementia caregivers Table 2. Relative hazard of incident dementia from spousal caregiving, adjusted for covariates. Parameter DF ML Parameter Estimate Standard Error Chi- Square Pr > ChiSq Hazard Ratio 95% Hazard Ratio Confidence Limits Spouse Dementia Caregiving 1 1.79272 0.50536 12.5842 0.0004 6.006 2.231 16.171 Female gender 1 -0.22712 0.13305 2.9140 0.0878 0.797 0.614 1.034 Age at baseline interview 1 0.06220 0.02486 6.2601 0.0123 1.064 1.014 1.117 APOE Genotype: * one ε4 allele 1 0.37347 0.13793 7.3318 0.0068 1.453 1.109 1.904 APOE Genotype: two ε4 alleles 1 1.51376 0.23700 40.7950 <.0001 4.544 2.855 7.230 Husband’s Occupation: ** Professional, Technical, Management 1 -0.45482 0.19274 5.5685 0.0183 0.635 0.435 0.926 Husband’s Occupation: Clerical, Sales 1 -0.41148 0.25922 2.5197 0.1124 0.663 0.399 1.101 Husband’s Occupation: Service 1 -0.02075 0.36752 0.0032 0.9550 0.979 0.477 2.013 Husband’s Occupation: Agriculture 1 -0.21729 0.18043 1.4503 0.2285 0.805 0.565 1.146 Husband’s education (years) 1 0.0003385 0.02394 0.0002 0.9887 1.000 0.954 1.048 * Reference category for APOE genotype was zero ε4 alleles ** Reference category for husband’s occupation was “Machine/miscellaneous” 21
  • 22. Incident dementia risk among spouse dementia caregivers ALTERNATIVE TABLE 2 Table 2. Relative hazard of incident dementia from spousal caregiving, adjusted for covariates (overall model in total sample of 2442 subjects, then stratified by spouse gender). Total Sample Husband as Index Subject Wife as Index Subject Parameter DF Hazard Ratio 95% Hazard Ratio Confidence Limits Hazard Ratio 95% Hazard Ratio Confidence Limits Hazard Ratio 95% Hazard Ratio Confidence Limits Spouse Dementia Caregiving 1 6.006 2.23 - 16.17 11.79 1.65 - 84.53 3.56 1.12 – 11.29 Female gender 1 0.797 0.61 - 1.03 ------- ------- ------- ------- Age at baseline interview 1 1.064 1.01 - 1.12 1.02 .98 – 1.07 1.13 1.05 – 1.23 APOE Genotype: * one ε4 allele 1 1.453 1.11 - 1.90 1.41 .99 – 2.01 1.44 .93 – 2.24 APOE Genotype: two ε4 alleles 1 4.544 2.86 - 7.23 4.61 2.53 – 8.40 3.76 1.65 – 8.58 Husband’s Occupation: ** Professional, Technical, Management 1 0.635 0.44 - 0.93 .68 .41 – 1.10 .63 .34 – 1.18 Husband’s Occupation: Clerical, Sales 1 0.663 0.40 - 1.10 .58 .29 – 1.18 .86 .41 – 1.82 Husband’s Occupation: Service 1 0.979 0.48 - 2.01 1.06 .43 – 2.63 .72 .21 – 2.51 Husband’s Occupation: Agriculture 1 0.805 0.57 - 1.15 .93 .59 – 1.47 .64 .35 – 1.16 Husband’s education (years) 1 1.000 0.95 - 1.05 .99 .94 – 1.06 .99 .92 – 1.07 22
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