Association of life-course traumatic brain injury with dementia risk: A nationwide twin study.
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ABSTRACT: Introduction
The impact of life-course traumatic brain injury (TBI) on dementia is unclear.Methods
Within the Swedish Twin Registry (STR), 35,312 dementia-free twins were followed for up to 18 years. TBI history was identified via medical records. Data were analyzed using generalized estimating equation (GEE) and conditional logistic regression.Results
In multi-adjusted GEE models, the odds ratio (OR, 95% confidence interval [CI]) of dementia was 1.27 (1.03-1.57) for TBI at any age, 1.55 (1.04-2.31) for TBI at 50 to 59 years, and 1.67 (1.12-2.49) for TBI at 60 to 69 years. Cardiometabolic diseases (CMDs) increased dementia risk associated with TBI at age 50 to 69 years. The ORs in GEE and conditional logistic regression did not differ significantly (P = .37).Discussion
TBI, especially between ages 50 and 69 years, is associated with an increased risk of dementia, and this is exacerbated among people with CMDs. Genetic and early-life environmental factors may not account for the TBI-dementia association.
SUBMITTER: Zhang L
PROVIDER: S-EPMC10078668 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
Publications
Association of life-course traumatic brain injury with dementia risk: A nationwide twin study.
Zhang Lulu L Yang Wenzhe W Li Xuerui X Dove Abigail A Qi Xiuying X Pan Kuan-Yu KY Xu Weili W
Alzheimer's & dementia : the journal of the Alzheimer's Association 20220328 1
<h4>Introduction</h4>The impact of life-course traumatic brain injury (TBI) on dementia is unclear.<h4>Methods</h4>Within the Swedish Twin Registry (STR), 35,312 dementia-free twins were followed for up to 18 years. TBI history was identified via medical records. Data were analyzed using generalized estimating equation (GEE) and conditional logistic regression.<h4>Results</h4>In multi-adjusted GEE models, the odds ratio (OR, 95% confidence interval [CI]) of dementia was 1.27 (1.03-1.57) for TBI ...[more]
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Project description:BackgroundTraumatic brain injury (TBI) has been associated with dementia. The questions of whether the risk of dementia decreases over time after TBI, whether it is similar for different TBI types, and whether it is influenced by familial aggregation are not well studied.Methods and findingsThe cohort considered for inclusion comprised all individuals in Sweden aged ≥50 years on December 31, 2005 (n = 3,329,360). Diagnoses of dementia and TBI were tracked through nationwide databases from 1964 until December 31, 2012. In a first cohort, individuals diagnosed with TBI (n = 164,334) were matched with up to two controls. A second cohort consisted of subjects diagnosed with dementia during follow-up (n = 136,233) matched with up to two controls. A third cohort consisted of 46,970 full sibling pairs with discordant TBI status. During a mean follow-up period of 15.3 (range, 0-49) years, 21,963 individuals in the first cohort (6.3% with TBI, 3.6% without TBI) were diagnosed with dementia (adjusted odds ratio [OR], 1.81; 95% confidence interval [CI], 1.75-1.86). The association was strongest in the first year after TBI (OR, 3.52; 95% CI, 3.23-3.84), but the risk remained significant >30 years (OR, 1.25; 95% CI, 1.11-1.41). Single mild TBI showed a weaker association with dementia (OR, 1.63; 95% CI, 1.57-1.70) than did more severe TBI (OR, 2.06; 95% CI, 1.95-2.19) and multiple TBIs (OR, 2.81; 95% CI, 2.51-3.15). These results were in general confirmed in the nested case-control cohort. TBI was also associated with an increased risk of dementia diagnosis in sibling pairs with discordant TBI status (OR, 1.89; 95% CI, 1.62-2.21). A main limitation of the present study is the observational design. Thus, no causal inferences can be made based on the associations found.ConclusionsThe risk of dementia diagnosis decreased over time after TBI, but it was still evident >30 years after the trauma. The association was stronger for more severe TBI and multiple TBIs, and it persisted after adjustment for familial factors.
| S-EPMC5790223 | biostudies-literature
Project description:ImportanceTraumatic brain injuries (TBIs) can have serious long-term consequences, including psychiatric disorders. However, few studies have assessed the association between TBI and risk of suicide.ObjectiveTo examine the association between TBI and subsequent suicide.Design, setting, and participantsRetrospective cohort study using nationwide registers covering 7 418 391 individuals (≥10 years) living in Denmark (1980-2014) with 164 265 624 person-years' follow-up; 567 823 (7.6%) had a medical contact for TBI. Data were analyzed using Poisson regression adjusted for relevant covariates, including fractures not involving the skull, psychiatric diagnoses, and deliberate self-harm.ExposureMedical contacts for TBI recorded in the National Patient Register (1977-2014) as mild TBI (concussion), skull fracture without documented TBI, and severe TBI (head injuries with evidence of structural brain injury).Main outcomes and measuresSuicide recorded in the Danish Cause of Death register until December 31, 2014.ResultsOf 34 529 individuals who died by suicide (mean age, 52 years [SD, 18 years]; 32.7% women; absolute rate 21 per 100 000 person-years [95% CI, 20.8-21.2]), 3536 (10.2%) had medical contact: 2701 with mild TBI, 174 with skull fracture without documented TBI, and 661 with severe TBI. The absolute suicide rate was 41 per 100 000 person-years (95% CI, 39.2-41.9) among those with TBI vs 20 per 100 000 person-years (95% CI, 19.7-20.1) among those with no diagnosis of TBI. The adjusted incidence rate ratio (IRR) was 1.90 (95% CI, 1.83-1.97). Compared with those without TBI, severe TBI (absolute rate, 50.8 per 100 000 person-years; 95% CI, 46.9-54.6) was associated with an IRR of 2.38 (95% CI, 2.20-2.58), whereas mild TBI (absolute rate, 38.6 per 100 000 person-years; 95% CI, 37.1-40.0), and skull fracture without documented TBI (absolute rate, 42.4 per 100 000 person-years; 95% CI, 36.1-48.7) had an IRR of 1.81 (95% CI, 1.74-1.88) and an IRR of 2.01 (95% CI, 1.73-2.34), respectively. Suicide risk was associated with number of medical contacts for TBI compared with those with no TBI contacts: 1 TBI contact, absolute rate, 34.3 per 100 000 person-years (95% CI, 33.0-35.7; IRR, 1.75; 95% CI, 1.68-1.83); 2 TBI contacts, absolute rate, 59.8 per 100 000 person-years (95% CI, 55.1-64.6; IRR, 2.31; 95% CI, 2.13-2.51); and 3 or more TBI contacts, absolute rate, 90.6 per 100 000 person-years (95% CI, 82.3-98.9; IRR, 2.59; 95% CI, 2.35-2.85; all P < .001 for the IRR's). Compared with the general population, temporal proximity since the last medical contact for TBI was associated with risk of suicide (P<.001), with an IRR of 3.67 (95% CI, 3.33-4.04) within the first 6 months and an incidence IRR of 1.76 (95% CI, 1.67-1.86) after 7 years.Conclusions and relevanceIn this nationwide registry-based retrospective cohort study individuals with medical contact for TBI, compared with the general population without TBI, had increased suicide risk.
| S-EPMC6142987 | biostudies-literature
Project description:BackgroundCardiometabolic diseases (CMDs) including heart disease, stroke, and type 2 diabetes have been individually linked to depression. However, their combined impact on depression risk is unclear. We aimed to examine the association between cardiometabolic multimorbidity and depression and explore the role of genetic background in this association.MethodsWithin the Swedish Twin Registry, 40,080 depression-free individuals (mean age 60 years) were followed for 18 years. Cardiometabolic multimorbidity was defined as having ≥2 CMDs. CMDs and depression were ascertained based on the National Patient Register. Cox regression was used to estimate the CMD-depression association in a classical cohort study design and a matched co-twin design involving 176 twin pairs. By comparing the associations between monozygotic and dizygotic co-twins, the contribution of genetic background was estimated.ResultsAt baseline, 4809 (12.0%) participants had one CMD and 969 (2.4%) had ≥2 CMDs. Over the follow-up period, 1361 participants developed depression. In the classical cohort design, the multi-adjusted hazard ratios (95% confidence interval [CIs]) of depression were 1.52 (1.31-1.76) for those with one CMD and 1.83 (1.29-2.58) for those with ≥2 CMDs. CMDs had a greater risk effect on depression if they developed in mid-life (<60 years) as opposed to late life (≥60 years). In matched co-twin analysis, the CMD-depression association was significant among dizygotic twins (HR = 1.63, 95% CI, 1.02-2.59) but not monozygotic twins (HR = 0.90, 95% CI, 0.32-2.51).ConclusionsCardiometabolic multimorbidity is associated with an elevated risk of depression. Genetic factors may contribute to the association between CMDs and depression.
| S-EPMC11457118 | biostudies-literature
Project description:ObjectiveTo investigate whether sex and race differences exist in dementia diagnosis risk associated with traumatic brain injury (TBI) among older veterans.MethodsUsing Fine-Gray regression models, we investigated incident dementia diagnosis risk with TBI exposure by sex and race.ResultsAfter the exclusion of baseline prevalent dementia, the final sample (all veterans ≥55 years of age diagnosed with TBI during the 2001-2015 study period and a random sample of all veterans receiving Veterans Health Administration care) included nearly 1 million veterans (4.3% female; 81.8% White, 11.5% Black, and 1.25% Hispanic), 96,178 with TBI and 903,462 without TBI. Compared to those without TBI, Hispanic veterans with TBI were almost 2 times more likely (17.0% vs 10.3%; hazard ratio [HR] 1.74, 95% confidence interval [CI] 1.51-2.01), Black veterans with TBI were >2 times more likely (11.2% vs 6.4%; HR 2.15, 95% CI 2.02-2.30), and White veterans with TBI were nearly 3 times more likely to receive a dementia diagnosis (12.0% vs 5.9%; HR 2.71, 95% CI 2.64-2.77). A significant interaction between TBI and race for dementia diagnosis was observed (p < 0.001). Both male and female veterans with TBI were more than twice as likely (men 11.8% vs 5.9%, HR 2.60, 95% CI 2.54-2.66; women 6.3% vs 3.1%, HR 2.36, 95% CI 2.08-2.69) to receive a diagnosis of dementia compared to those without. There was a significant interaction effect between sex and TBI (p = 0.02), but the magnitude of differences was small.ConclusionsIn this large, nationwide cohort of older veterans, all race groups with TBI had increased risk of dementia diagnosis, but there was an interaction effect such that White veterans were at greatest risk for dementia after TBI. Further research is needed to understand the mechanisms for this discrepancy. Differences in dementia diagnosis risk for men and women after TBI were significant but small, and male and female veterans had similarly high risks of dementia diagnosis after TBI.
| S-EPMC7682824 | biostudies-literature
Project description:ImportanceThe late effects of traumatic brain injury (TBI) are of great interest, but studies characterizing these effects are limited.ObjectiveTo determine whether TBI with loss of consciousness (LOC) is associated with an increased risk for clinical and neuropathologic findings of Alzheimer disease (AD), Parkinson disease (PD), and other dementias.Design, setting, and participantsThis study analyzed data from the Religious Orders Study (ROS), Memory and Aging Project (MAP), and Adult Changes in Thought study (ACT). All ROS and MAP participants and a subset of ACT participants consent to autopsy. Studies performed annual (ROS and MAP) or biennial (ACT) cognitive and clinical testing to identify incident cases of dementia and AD. The 7130 participants included members of a Seattle-area health care delivery system (ACT), priests and nuns living in orders across the United States (ROS), and Chicago-area adults in retirement communities (MAP). Of these, 1589 underwent autopsy. Primary hypothesis was that TBI with LOC would be associated with increased risk for AD and neurofibrillary tangles. Data were accrued from 1994 to April 1, 2014.ExposuresSelf-reported TBI when the participant was free of dementia, categorized as no more than 1 vs more than 1 hour of LOC.Main outcomes and measuresClinical outcomes included incident all-cause dementia, AD, and PD in all studies and incident mild cognitive impairment and progression of parkinsonian signs in ROS and MAP. Neuropathologic outcomes included neurofibrillary tangles, neuritic plaques, microinfarcts, cystic infarcts, Lewy bodies, and hippocampal sclerosis in all studies.ResultsOf 7130 participants (2879 [40.4%] men; overall mean [SD] age, 79.9 [6.9] years), 865 reported a history of TBI with LOC. In 45 190 person-years of follow-up, 1537 incident cases of dementia and 117 of PD were identified. No association was found between TBI with LOC and incident dementia (ACT: HR for TBI with LOC ≤1 hour, 1.03; 95% CI, 0.83-1.27; HR for TBI with LOC >1 hour, 1.18; 95% CI, 0.77-1.78; ROS and MAP: HR for TBI with LOC ≤1 hour, 0.87; 95% CI, 0.58-1.29; HR for TBI with LOC >1 hour, 0.84; 95% CI, 0.44-1.57) or AD (findings similar to those for dementia). Associations were found for TBI with LOC and incident PD in ACT (HR for TBI with LOC >1 hour, 3.56; 95% CI, 1.52-8.28) and progression of parkinsonian signs in ROS and MAP (odds ratio [OR] for TBI with LOC ≤1 hour, 1.65; 95% CI, 1.23-2.21; OR for TBI with LOC >1 hour, 2.23; 95% CI, 1.16-4.29). Traumatic brain injury with LOC was associated with Lewy bodies (any Lewy body in ACT: RR for TBI with LOC >1 hour, 2.64; 95% CI, 1.40-4.99; Lewy bodies in substantia nigra and/or locus ceruleus in ACT: RR for TBI with LOC >1 hour, 3.30; 95% CI, 1.71-6.38; Lewy bodies in frontal or temporal cortex in ACT: RR for TBI with LOC >1 hour, 5.73; 95% CI, 2.18-15.0; ROS and MAP: RR for TBI with LOC ≤1 hour, 1.64; 95% CI, 1.00-2.70; pooled RR for TBI with LOC ≤1 hour, 1.59; 95% CI, 1.06-2.39) and microinfarcts (any cortical microinfarct in ROS and MAP: RR for TBI with LOC >1 hour, 2.12; 95% CI, 1.12-4.01; pooled RR for TBI with LOC >1 hour, 1.58; 95% CI, 1.06-2.35).Conclusions and relevancePooled clinical and neuropathologic data from 3 prospective cohort studies indicate that TBI with LOC is associated with risk for Lewy body accumulation, progression of parkinsonism, and PD, but not dementia, AD, neuritic plaques, or neurofibrillary tangles.
| S-EPMC5319642 | biostudies-literature
Project description:ObjectivesTraumatic brain injury (TBI) and perinatal adversities such as low gestational age at birth, low birth weight, low Apgar, and being born small for gestational age are well-established risk factors for epilepsy. We examined whether perinatal adversities modified the risk of epilepsy after TBI in a nationwide cohort study of Danish singletons born from 1982 to 2011.Materials and methodsWe categorized perinatal adversities as a composite measure of preterm delivery, low birth weight, low Apgar score, or being born small for gestational age. Cox regression and competing risk regression were used to estimate the risk of epilepsy after TBI according to such perinatal adversities. The study included 1,715,095 singletons (51.1% males). The mean age at end of follow-up was 19.3 years (Interquartile range [IQR] = 12.1-26.3). During follow-up, 85,636 persons (58.2% males) sustained a TBI and 18,064 developed epilepsy (50.7% males), of whom 1329 persons had a preceding TBI.ResultsThe hazard ratio (HR) of epilepsy in persons with perinatal adversities was 1.19 (95% confidence interval [CI] 1.15-1.24), compared to persons without. The HR of epilepsy in persons with TBI was 2.31 (95% CI 2.18-2.45) compared to persons without TBI, but this risk was not modified by perinatal adversities (p = 0.2460).ConclusionsPerinatal adversities and TBI both increased the risk of epilepsy, but the risk of epilepsy after TBI was not modified by these perinatal adversities.
| S-EPMC9311430 | biostudies-literature
Project description:Post-traumatic headache is common after pediatric traumatic brain injury and affects thousands of children every year, but little is known about how headache affects recovery after traumatic brain injury in other symptom domains. We aimed to determine the association between headache and other common symptoms after pediatric traumatic brain injury and explore whether subjective complaints of headache are associated with objective deficits on specialized neurocognitive testing. We conducted a retrospective cohort study of children ages 3-19 years following traumatic brain injury with a completed Sports Concussion Assessment Tool (SCAT) questionnaire. Post-traumatic headache was defined by a score more than 2 on the SCAT question for headache and define headache groups for comparison. In our cohort, we analyzed data from the Delis-Kaplan Executive Function System and the Wechsler Abbreviated Scale of Intelligence, Second Edition (WASI-II). Headache was reported in 40 (33%) patients presenting for post-traumatic brain injury care among 121 pediatric traumatic brain injury patients and did not differ by injury severity. Median total SCAT symptom score in the headache group was 5-fold higher compared to patients without headache (median 45.5 vs 9; P < .001). Significantly lower-scaled scores in color naming, matrix reasoning, letter sequencing, and letter switching were also found in the headache group (all P ≤ .03). Our study shows that headache, as reported by patients on the SCAT, is associated with higher symptom scores in all other symptom domains, including sleep, mood, sensory, and cognitive. Headache was also associated with worse objective neurocognitive measures and may identify patients who could benefit from specialized follow-up care and management.
| S-EPMC7308075 | biostudies-literature
Project description:IntroductionTraumatic brain injury (TBI) may alter the course of neuropsychiatric symptom (NPS) onset during dementia development. The connection among TBI, NPS, and dementia progression is of increasing interest to researchers and clinicians.MethodsIncidence of NPS was examined in participants with normal cognition who progressed to all-cause dementia based on whether TBI history was present (n = 130) or absent (n = 849). Survival analyses were used to examine NPS incidence across 7.6 ± 3.0 years of follow-up.ResultsParticipants with TBI history had increased prevalence and incidence of apathy (44.7% vs 29.9%, P = .0062; HRadj. = 1.708, P = .0018) and motor disturbances (17.2% vs 9.5%, P = .0458; HRadj. = 2.023, P = .0168), controlling for demographics and type of dementia diagnosis. Earlier anxiety onset was associated with TBI (692 days prior to dementia diagnosis vs 161 days, P = .0265).DiscussionHistory of TBI is associated with increased risk for and earlier onset of NPS in the trajectory of dementia development.
| S-EPMC8043985 | biostudies-literature
Project description:BackgroundWe aimed to examine the temporal relationships between traumatic events (TE), post-traumatic stress disorder (PTSD) and non-affective psychotic disorders (NAPD).MethodsA prospective cohort study of 1 965 214 individuals born in Sweden between 1971 and 1990 examining the independent effects of interpersonal and non-interpersonal TE on incidence of PTSD and NAPD using data from linked register data (Psychiatry-Sweden). Mediation analyses tested the hypothesis that PTSD lies on a causal pathway between interpersonal trauma and NAPD.ResultsIncreasing doses of interpersonal and non-interpersonal TE were independently associated with increased risk of NAPD [linear-trend incidence rate ratios (IRR)adjusted = 2.17 [95% confidence interval (CI) 2.02-2.33] and IRRadjusted = 1.27 (95% CI 1.23-1.31), respectively]. These attenuated to a relatively small degree in 5-year time-lagged models. A similar pattern of results was observed for PTSD [linear-trend IRRadjusted = 3.43 (95% CI 3.21-3.66) and IRRadjusted = 1.45 (95% CI 1.39-1.50)]. PTSD was associated with increased risk of NAPD [IRRadjusted = 8.06 (95% CI 7.23-8.99)], which was substantially attenuated in 5-year time-lagged analyses [IRRadjusted = 4.62 (95% CI 3.65-5.87)]. There was little evidence that PTSD diagnosis mediated the relationship between interpersonal TE and NAPD [IRRadjusted = 0.92 (percentile CI 0.80-1.07)].ConclusionDespite the limitations to causal inference inherent in observational designs, the large effect-sizes observed between trauma, PTSD and NAPD in this study, consistent across sensitivity analyses, suggest that trauma may be a component cause of psychotic disorders. However, PTSD diagnosis might not be a good proxy for the likely complex psychological mechanisms mediating this association.
| S-EPMC10009379 | biostudies-literature
Project description:BackgroundPrior studies into the association of head trauma with neuropathology have been limited by incomplete lifetime neurotrauma exposure characterization.ObjectiveTo investigate the neuropathological sequelae of traumatic brain injury (TBI) in an autopsy sample using three sources of TBI ascertainment, weighting findings to reflect associations in the larger, community-based cohort.MethodsSelf-reported head trauma with loss of consciousness (LOC) exposure was collected in biennial clinic visits from 780 older adults from the Adult Changes in Thought study who later died and donated their brain for research. Self-report data were supplemented with medical record abstraction, and, for 244 people, structured interviews on lifetime head trauma. Neuropathology outcomes included Braak stage, CERAD neuritic plaque density, Lewy body distribution, vascular pathology, hippocampal sclerosis, and cerebral/cortical atrophy. Exposures were TBI with or without LOC. Modified Poisson regressions adjusting for age, sex, education, and APOE ɛ4 genotype were weighted back to the full cohort of 5,546 participants.ResultsTBI with LOC was associated with the presence of cerebral cortical atrophy (Relative Risk 1.22, 95% CI 1.02, 1.42). None of the other outcomes was associated with TBI with or without LOC.ConclusionTBI with LOC was associated with increased risk of cerebral cortical atrophy. Despite our enhanced TBI ascertainment, we found no association with the Alzheimer's disease-related neuropathologic outcomes among people who survived to at least age 65 without dementia. This suggests the pathophysiological processes underlying post-traumatic neurodegeneration are distinct from the hallmark pathologies of Alzheimer's disease.
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