Medical and environmental risk factors associated with frontotemporal dementia: A case‐control study in a veteran population

Kalkonde, Yogeshwar; Jawaid, Ali; Qureshi, Salah U.; Shirani, Peyman; Wheaton, Michael; Pinto-Patarroyo, Gineth P.; Schulz, Paul E.

doi:10.1016/j.jalz.2011.03.011

Cited by 92 publications

(78 citation statements)

References 40 publications

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“…FTD is the second most common form of early-onset dementia (Seelaar et al, 2011;Sieben et al, 2012). Several genetic mutations are reported in FTD; however, these findings only explain 20-40% of FTD cases with a positive family history (McKhann et al, 2001;Kalkonde et al, 2012). In the remaining 60-80% of sporadic FTD cases, the true pathophysiological mechanisms remain unclear (McKhann et al, 2001;Seelaar et al, 2011;Kalkonde et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, TBI has been implicated as a possible risk factor for several neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease, and amyotrophic lateral sclerosis (ALS) (Maas et al, 2008;Wang et al, 2012a,b). Previous studies suggested an increased risk of frontotemporal dementia (FTD) in patients with TBI (Rosso et al, 2003;Kalkonde et al, 2012); however, because of relatively small sample sizes, they could not exclude recall bias as a factor in the observed association. Therefore, how TBI contributes to FTD remains undetermined.…”

Section: Introductionmentioning

confidence: 93%

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Traumatic brain injury causes frontotemporal dementia and TDP-43 proteolysis

et al. 2015

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 93%

Traumatic brain injury causes frontotemporal dementia and TDP-43 proteolysis

et al. 2015

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“…26 Finally, a study of veterans seen at VA Cognitive Disorders Clinics found that TBIs were more than 4 times more likely to be present in FTD than other forms of dementia such as AD, VaD, and dementia with Lewy bodies. 27 A limitation of prior studies in both veteran and nonveteran populations is that they did not account for the competing risk of death. Our study adds to the existing literature by finding that there is a consistent association between TBI in older veterans and the subsequent risk of developing dementia, even after accounting for mortality as a competing risk.…”

Section: Traumatic Brain Injurymentioning

confidence: 99%

“…28,33 The neuropathology of chronic traumatic encephalopathy, whether seen in athletes with repeated sports injuries or veterans with repeated blast injuries, 34 includes prominent accumulation of tau in the form of neurofibrillary tangles, which are located and distributed differently from the neurofibrillary tangles seen in AD. 28 Furthermore, yet other work has suggested that TBI may predispose individuals to FTD more than other dementias, 27 possibly related to alterations in levels of the protein progranulin that occur after TBI and Table 3 Unadjusted and adjusted risk of dementia from Fine-Gray Cox proportional hazards models Age at dementia diagnosis in veterans with and without TBI, accounting for mortality…”

Section: Traumatic Brain Injurymentioning

confidence: 99%

Traumatic brain injury and risk of dementia in older veterans

et al. 2014

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Objectives: Traumatic brain injury (TBI) is common in military personnel, and there is growing concern about the long-term effects of TBI on the brain; however, few studies have examined the association between TBI and risk of dementia in veterans.Methods: We performed a retrospective cohort study of 188,764 US veterans aged 55 years or older who had at least one inpatient or outpatient visit during both the baseline (2000)(2001)(2002)(2003) and follow-up (2003-2012) periods and did not have a dementia diagnosis at baseline. TBI and dementia diagnoses were determined using ICD-9 codes in electronic medical records. Fine-Gray proportional hazards models were used to determine whether TBI was associated with greater risk of incident dementia, accounting for the competing risk of death and adjusting for demographics, medical comorbidities, and psychiatric disorders.Results: Veterans were a mean age of 68 years at baseline. During the 9-year follow-up period, 16% of those with TBI developed dementia compared with 10% of those without TBI (adjusted hazard ratio, 1.57; 95% confidence interval: 1.35-1.83). There was evidence of an additive association between TBI and other conditions on risk of dementia.Conclusions: TBI in older veterans was associated with a 60% increase in the risk of developing dementia over 9 years after accounting for competing risks and potential confounders. Our results suggest that TBI in older veterans may predispose toward development of symptomatic dementia and raise concern about the potential long-term consequences of TBI in younger veterans and civilians. There is growing evidence that traumatic brain injury (TBI) is associated with a variety of shortand long-term adverse health outcomes. A 2008 Institute of Medicine report concluded that TBIs are consistently associated with an increased risk of unprovoked seizures, premature mortality, and neurocognitive deficits in the affected region, with evidence strongest for penetrating wounds and severe or moderate TBIs.1 However, prior research on the relationship between TBI and risk of Alzheimer disease (AD) and all-cause dementia has been mixed. [2][3][4][5][6][7][8][9][10][11][12][13][14] Most prior studies have not adequately controlled for potential confounders, such as medical and psychiatric comorbidities, and none have considered death as a competing risk.Furthermore, to our knowledge, only one prior study has specifically focused on examining the relationship between TBI and risk of dementia in veterans.11 Many veterans have other combatrelated risk factors such as posttraumatic stress disorder (PTSD) and depression, which have been associated with an increased risk of dementia in veterans in prior studies, 15,16 and could act as either confounders or effect modifiers of the association between TBI and dementia in veterans.

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“…37,38 While repetitive concussions have been linked to progressive neuropsychiatric symptoms, cognitive deficits, and pathologic tau deposition in the frontal and temporal lobes in chronic traumatic encephalopathy, 39 the relationship of isolated concussion or mild head injury in relation to chronic traumatic encephalopathy and other forms of FTD…”

Section: Environmentalmentioning

confidence: 99%