Traumatic Brain Injury Exposure Lowers Age of Cognitive Decline in AD and Non-AD Conditions

Abstract

We aimed to detect the possible accelerating role of previous traumatic brain injury (TBI) exposures on the onset of later cognitive decline assessed across different brain diseases. We analyzed data from the National Alzheimer's Coordinating Center (NACC), which provide information on history of TBI and longitudinal data on cognitive and non-cognitive domains for each available subject. At the time of this investigation, a total of 609 NACC subjects resulted to have a documented history of TBI. We compared subjects with and without a history of previous TBI (of any type) at the time of their first cognitive decline assessment, and termed them, respectively, TBI+ and TBI- subjects. Three hundred and sixty-one TBI+ subjects (229 male/132 female) and 248 TBI- subjects (156 male/92 female) were available. The analyses included TBI+ and TBI- subjects with a clinical diagnosis of Mild Cognitive Impairment, Alzheimer's disease, Dementia with Lewy bodies, Progressive supranuclear palsy, Corticobasal degeneration, Frontotemporal dementia, Vascular dementia, non-AD Impairment, and Parkinson's disease. The data showed that the mean age of TBI+ subjects was lower than TBI- subjects at the time of their first cognitive decline assessment (71.6 ± 11.2 vs. 74.8 ± 9.5 year; p < 0.001). Moreover, the earlier onset of cognitive decline in TBI+ vs. TBI- subjects was independent of sex, race, attained education, APOE genotype, and importantly, clinical diagnoses. As for specific cognitive aspects, MMSE, Trail Making Test part B and WAIS-R scores did not differ between TBI+ and TBI- subjects, whereas Trail Making Test part A (p = 0.013) and Boston Naming test (p = 0.008) did. In addition, data showed that neuropsychiatric symptoms [based on Neuropsychiatry Inventory (NPI)] were much more frequent in TBI+ vs. TBI- subjects, including AD and non-AD neurodegenerative conditions such as PD. These cross-sectional analyses outcomes from longitudinally-assessed cohorts of TBI+ subjects that is, subjects with TBI exposure before the onset of cognitive decline in the contest of different neurodegenerative disorders and associated pathogenetic mechanisms, are novel, and indicate that a previous TBI exposure may act as a significant "age-lowering" factor on the onset of cognitive decline in either AD and non-AD conditions independently of demographic factors, education, APOE genotype, and current or upcoming clinical conditions.

Keywords: APOE genotype; TBI; cognitive decline; earlier-onset; neurodegenerative disorders.

Figure 1

The figure shows bar plots of the mean scores for the Mini Mental Status Examination (MMSE), Trail Making Test part A and B (TMT-A, TMT-B), WAIS-R scale and Boston Naming Test for both TBI+ (subjects with a previous history of TBI at the time of their first cognitive decline assessment) and TBI– (subjects without a previous history of TBI at the time of their first cognitive decline assessment) as clustered by their associated clinical diagnosis at the time of their first cognitive decline assessment. MCI, Mild cognitive impairment, Dementia [including Alzheimer's disease (AD), Dementia with Lewy bodies (DLB), Progressive supranuclear palsy (PSP), Corticobasal degeneration (CBD), Frontotemporal Dementia (FTD), Vascular dementia (VaD), Traumatic brain Injury (TBI), normal pressure hydrocephalus (NPH), Depression, Cognitive decline due to systematic disease or medical illness], non-AD Impairment (Impaired). For TMT-A (p = 0.013) and Boston Naming test (p = 0.008) a significance was found TBI+ vs. TBI– groups. *indicates the presence of statistical significance (p-values <0.05).

Figure 2

(A) The figure shows bar plots of the mean scores for the Neuropsychiatric Inventory (NPI) for both TBI+ (subjects with a previous history of TBI at the time of their first cognitive decline assessment) and TBI– (subjects without a previous history of TBI at the time of their first cognitive decline assessment) as clustered by their associated clinical diagnosis at the time of their first cognitive decline assessment. MCI, Mild cognitive impairment, Dementia [including Alzheimer's disease (AD), Dementia with Lewy bodies (DLB), Progressive supranuclear palsy (PSP), Corticobasal degeneration (CBD), Frontotemporal Dementia (FTD), Vascular dementia (VaD), Traumatic brain Injury (TBI), normal pressure hydrocephalus (NPH), Depression, Cognitive decline due to systematic disease or medical illness], non-AD Impairment (Impaired). A trend for TBI+ subjects with a diagnosis of MCI and Impaired to have a higher frequency of neuropsychiatric disorders and symptoms as mostly listed in the NPI was observed. (B) The histograms show percentages (%) of frequency for NPI-based neuropsychiatric disorders in TBI– and TBI+ groups across all subjects (upper and lower left panels) and PD subjects (upper and lower right panels).

Figure 3

(A) The figure shows horizontal stacked bars for the description of the relative frequencies of the different APOE in both TBI+ (subjects with a previous history of TBI at the time of their first cognitive decline assessment) and TBI– (subjects without a previous history of TBI at the time of their first cognitive decline assessment) as clustered by their associated clinical diagnosis at the time of their first cognitive decline assessment. MCI: Mild cognitive impairment, Dementia [including Alzheimer's disease (AD), Dementia with Lewy bodies (DLB), Progressive supranuclear palsy (PSP), Corticobasal degeneration (CBD), Frontotemporal Dementia (FTD), Vascular dementia (VaD), Traumatic brain Injury (TBI), normal pressure hydrocephalus (NPH), Depression, Cognitive decline due to systematic disease or medical illness], non-AD Impairment (Impaired). (B) The table in the figure shows the general APOE allelic frequencies (APOE2, E3, E4) in both TBI+ and TBI– subjects in the analyzed NACC's TBI cohort.

Figure 4

(A) The figure shows bar plots for the UPDRS-Motor scale across all TBI+ (subjects with a previous history of TBI at the time of their first cognitive decline assessment) and TBI– (subjects without a previous history of TBI at the time of their first cognitive decline assessment) as clustered by their associated clinical diagnosis at the time of their first cognitive decline assessment. MCI, Mild cognitive impairment, Dementia [including Alzheimer's disease (AD), Dementia with Lewy bodies (DLB), Progressive supranuclear palsy (PSP), Corticobasal degeneration (CBD), Frontotemporal Dementia (FTD), Vascular dementia (VaD), Traumatic brain Injury (TBI), normal pressure hydrocephalus (NPH), Depression, Cognitive decline due to systematic disease or medical illness], non-AD Impairment (Impaired). (B) The figure shows bar plots for the UPDRS-Motor scale in TBI+ and TBI– subjects with a diagnosis of Parkinson's disease (PD) at the time of their first cognitive decline assessment. Both TBI+/PD/MCI and TBI+/PD/Impaired subjects showed higher mean scores vs. TBI–/PD/MCI and TBI–/PD/Impaired subjects. (C) The two waffle graphs show the counts and corresponding proportions of MCI, Dementia and Impaired subjects with a diagnosis of PD with (TBI+) and without (TBI–) a history of TBI prior to their first cognitive decline assessment.