Interaction between Apolipoprotein epsilon 4 and traumatic brain injury in patients with Alzheimer's disease and Mild Cognitive Impairment.
ABSTRACT Several pathogenetic factors seem to contribute to the development of Alzheimer's disease (AD). Some data point to a role for traumatic brain injury (TBI), but this suggestion is not universally supported. Mayeux et al. have shown that TBI increases the risk of AD, but only through a synergistic relationship with apolipoprotein epsilon (Apo E) 4. We present the results of a cross-sectional and longitudinal study of the relationship between these factors, conducted in northern and southern Italy. We studied 337 consecutive patients with probable AD and 63 subjects with mild cognitive impairment (MCI). Information concerning head injuries was collected by interview of informants and review of medical records. Twenty-one patients with AD and 9 with MCI were found to have a history of TBI with loss of consciousness. AD and MCI patients with a history of TBI, compared with control groups matched for age, sex, education and degree of mental impairment, showed more marked depressive and behavioural disturbances (Global Deterioration Scale and Neuropsychiatric Inventory, p<0.05). Six- and 12-month follow up of both groups did not show significant differences in the rate of progression of cognitive changes. A high frequency of Apo E 4 was detected in the patients with TBI and cognitive impairment (40.5% in the AD and 11% in the MCI subgroups). The distribution of the epsilon 4 allele in our control group was 4%, comparable to that found in the Italian population. Distribution of the above parameters was similar in patients from northern and southern Italy. The higher frequency of TBI and Apo E 4 genotype among AD and MCI patients confirms the synergistic interaction of environmental and genetic factors in the development of dementia. Our data do not suggest that the presence of these two factors influences the clinical presentation or the course of the disease.
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ABSTRACT: Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in the United States, and the incidence has been increasing within the geriatric age group as the population ages. There are many factors that are unique to this subgroup, including normal aging processes, differences in pathophysiology, and inherent medical comorbidities that affect their outcomes, treatment, and therefore, the allocation of medical and social services. The geriatric population has age-appropriate strength, coordination and balance deficits that make them predisposed to falls and subsequent TBI. The aging brain often has premorbid atrophy and increased susceptibility to the inflammatory, excitatory, and vascular processes that facilitate neurologic damage during the acute phases after injury. The aged also can have premorbid neurodegenerative and medical comorbidities that also affect their rehabilitation course, recovery, and outcomes once a TBI has occurred. Pharmacological strategies to maximize rehabilitation and recovery require specific considerations of the potential for adverse effects and contraindications specific to common comorbidities in the aged population. The management of geriatric TBI requires a coordinated effort between physicians and other healthcare providers with focus on risk factor modification, medical optimization, and successful return to the community by setting goals that emphasize level of function and quality of life.09/2012; 1(3). DOI:10.1007/s13670-012-0021-6
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ABSTRACT: Cognitive impairments are common sequelae of traumatic brain injury (TBI) and are often associated with the natural process of aging. Few studies have examined the effect of both age and TBI on cognitive functioning. The purpose of this study was to compare cognitive functioning between older adults who sustained a TBI to an age-matched group of individuals without a brain injury and to determine whether the presence or absence of a genetic marker apolipoprotein epsilon (APOEepsilon4 allele) accounts for additional cognitive decline in both groups examined. Cognitive performance was measured by 11 neuropsychological tests, in 54 adults with TBI aged 55 and older and 40 age-matched control participants. All participants were reexamined 2 to 5 years later. Community volunteer-based sample examined at a large, urban medical center. California Verbal Learning Test; Wechsler Memory Scale-III (Logical Memory I & II; Visual Reproduction I & II); Grooved Pegboard; Woodcock-Johnson Test of Cognitive Ability (Visual Matching and Cross-out); Wisconsin Card Sorting Test; Trail Making Test A & B; Conners' Continuous Performance Task; Wechsler Adult Intelligence Scale-III (Vocabulary); Controlled Oral Word Association Test; and Boston Naming Test. Participants with TBI had lower scores on tests of attention and verbal memory than did participants with no disability. Neither group exhibited a significant decline in cognitive function over time. The presence of the APOEepsilon4 allele did not account for additional decline in cognitive function in either group. The findings suggest that older adults with TBI may not be at increased risk for cognitive decline over short time periods (2 to 5 years) even if they are carriers of the APOEepsilon4 allele.Journal of Head Trauma Rehabilitation 04/2008; 23(3):139-48. DOI:10.1097/01.HTR.0000319930.69343.64 · 3.00 Impact Factor
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ABSTRACT: To assess prospectively the degree of postrecovery long-term cognitive decline after moderate to severe traumatic brain injury (TBI). Observational cohort. Inpatient rehabilitation hospital. Adults (N=33) with moderate and severe TBI from a well characterized sample with low attrition. Not applicable. Recovery of functioning was ascertained through repeat neuropsychological assessments over the first 5 years postinjury. Cognitive decline from a baseline of 12 months postinjury to a follow-up evaluation conducted on average +/- SD 2.1+/-0.99 years later. Change was calculated using the reliable change index (RCI) for 12 neuropsychological tests commonly used in the assessment of TBI. At the group level, negligible changes in cognitive function were observed over time. However, application of the RCI using 90% confidence intervals showed statistically significant cognitive decline on at least 2 neuropsychological measures in 27.3% of study participants. Decline was most commonly observed on a test of verbal fluency and the delayed recall portion of a test of verbal list learning (Rey Auditory Verbal Learning Test), although substantial variability existed across patients. Decline was significantly correlated with hours of therapy received at 5 months postinjury (P<.02). Consistent with a small number of previous studies, cognitive deterioration may follow an initial period of recovery. Overall, the pattern of decline across tests varied across individuals. Possible mechanisms of decline are discussed. Further research is needed to understand the stability of this finding and its functional implications.Archives of physical medicine and rehabilitation 12/2008; 89(12 Suppl):S25-34. DOI:10.1016/j.apmr.2008.07.004 · 2.44 Impact Factor