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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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Preserved cognitive performance is a key feature of successful aging. Several theoretical models (compensation, hemispheric asymmetry reduction, and posterior-anterior shift) have been proposed to explain the putative underlying relationship between brain function and performance. We aimed to review imaging studies of the association between brain functional response and cognitive performance among healthy younger and older adults in order to understand the neural correlates of successful cognitive aging. MEDLINE-indexed articles published between January 1989 and May 2008, and bibliographies of these articles and related reviews were searched. Studies that measured brain function using fMRI or PET, evaluated cognitive performance, analyzed how cognitive performance related to brain response, and studied healthy older individuals were included. Forty-seven of 276 articles met these criteria. Eighty-one percent of the studies reported some brain regions in which greater activation related to better cognitive performance among older participants. This association was not universal, however, and was seen mainly in frontal cortex brain response and seemed to be more common among older compared to younger individuals. This review supports the notion of compensatory increases in brain activity in old age resulting in better cognitive performance, as suggested by hemispheric asymmetry reduction and posterior-anterior shift models of functional brain aging. However, a simple model of bigger structure → greater brain response → better cognitive performance may not be accurate. Suggestions for future research are discussed.

Background: Few studies have examined impairment in multiple senses (multisensory impairment) and risk of dementia in comparison to having a single or no sensory impairment. Methods: We studied 1,810 black and white nondemented participants from Health, Aging, and Body Composition (Health ABC) Study aged 70-79 years at enrollment. Sensory impairment was determined at our study baseline (Year 3-5 of Health ABC) using established cut points for vision (Bailey-Lovie visual acuity and Pelli-Robson contrast sensitivity test), hearing (audiometric testing), smell (12-item Cross-Cultural Smell Identification Test), and touch (peripheral nerve function tests). Incident dementia over 10 years of follow-up was based on hospitalization records, dementia medications, or at least 1.5 SD decline in Modified Mini-Mental State Examination score (race-specific). Cox proportional hazard models with adjustment for demographics, health behaviors, and health conditions evaluated the relationship between risk of dementia and increasing number of sensory impairments. Results: Sensory impairments were common: 28% had visual impairment, 35% had hearing loss, 22% had poor smell, 12% had touch insensitivity; 26% had more than two impairments, and 5.6% had more than three sensory impairments. Number of impairments was associated with risk of dementia in a graded fashion (p < .001). Compared to no sensory impairments, the adjusted hazard ratio was 1.49 (95% CI: 1.12, 1.98) for one sensory impairment, 1.91 (95% CI: 1.39, 2.63) for two sensory impairments, and 2.85 (95% CI: 1.88, 4.30) for more than three sensory impairments. Conclusions: Multisensory impairment was strongly associated with increased risk of dementia. Although, the nature of this relationship needs further investigation, sensory function assessment in multiple domains may help identify patients at high risk of dementia.

Cortical surface area measures appear to be functionally relevant and distinct in etiology, development, and behavioral correlates compared with other size characteristics, such as cortical thickness. Little is known about genetic and environmental influences on individual differences in regional surface area in humans. Using a large sample of adult twins, we determined relative contributions of genes and environment on variations in regional cortical surface area as measured by magnetic resonance imaging before and after adjustment for genetic and environmental influences shared with total cortical surface area. We found high heritability for total surface area and, before adjustment, moderate heritability for regional surface areas. Compared with other lobes, heritability was higher for frontal lobe and lower for medial temporal lobe. After adjustment for total surface area, regionally specific genetic influences were substantially reduced, although still significant in most regions. Unlike other lobes, left frontal heritability remained high after adjustment. Thus, global and regionally specific genetic factors both influence cortical surface areas. These findings are broadly consistent with results from animal studies regarding the evolution and development of cortical patterning and may guide future research into specific environmental and genetic determinants of variation among humans in the surface area of particular regions.

Unimpaired cognition is an important feature of successful aging. Differences in cognitive performance among healthy older adults may be related to differences in brain structure. We reviewed the literature to examine the relationship between brain structure size and cognitive performance in older adults. Eighty-three percent of studies found at least one positive relationship between these factors; however, findings were variable. Positive relationships emerged most consistently between the hippocampal formation and global cognition and memory and between frontal measures and executive function. Additional longitudinal study is needed to further evaluate structure-cognition relationships in older adulthood and across the adult lifespan.

SMCs are associated with cognitive impairment nearly 2 decades later among older women. SMCs may be a very early symptom of an insidious neurodegenerative disease process, such as Alzheimer disease.