Abstract Objective: To determine if cognitive performance over time is related to the APOE4 allele in non-demented individuals aged 90 and older. Background APOE4 is a major risk factor for developing Alzheimer's Disease. APOE4 may also serve as a predictor of significantly lower levels of cognitive performance among individuals age 90 and older. Design/Methods: Participants were 384 non-demented individuals in The 90+ Study, a population-based longitudinal study of people aged 90 and older. Included participants were APOE genotyped, non-demented at their last in-person visit, and had completed cognitive testing every six months. Global cognition was assessed using the Modified Mini-Mental State Exam (3MS) and memory was assessed using the California Verbal Learning Test-10 min delay (CVLT). Two random effects models were fitted to estimate the overall effect of the APOE4 allele on longitudinal cognitive performance. Model 1 examined cognitive performance over time and model 2 examined the added effect of APOE4 and related interactions on cognitive performance over time. The log likelihood of model 1 and model 2 were compared with a Likelihood Ratio Test (LRT). Results: Participants were on average 93 years of age at their first visit, 66% were women, and 15% had an APOE4 allele. The average follow up was 2 years (range: 0 years to 7 years). At baseline, the average MMSE score was 91 and average CVLT score was 6. There were no significant differences by APOE4 status on the 3MS (LRT: p ≥0.50) or CVLT (LRT: p ≥ 0.22) in non-demented oldest-old. Conclusions: In the non-demented oldest-old, APOE4 status does not appear to be a significant predictor of cognitive performance. Factors other than APOE4 status, such as health conditions or medication usage may be related to cognitive performance over time after age 90. Supported by: NIH grant R01AG21055.

People aged 90 years and older (oldest old), the fastest growing segment of the United States population, are known to have high rates of spells of all types, including strokes, transient ischemic attacks, and seizures. This study examined the prevalence of EEG abnormalities in 12 physically and cognitively healthy oldest old (mean age = 94 years) with no history of seizures or spells. Abnormalities were found in 83% of participants: temporal intermittent polymorphic slowing was seen in 67%, background slowing (alpha rhythm <8 Hz) was present in 33%, and temporal intermittent rhythmic delta was found in 17%. The high rates of EEG abnormalities found in these physically and cognitively healthy participants prompt reappraisal of pathologic significance in this unique population.

Objective

While traumatic brain injury (TBI) is common across the life span, the detailed neurobehavioral characteristics of older adults with prior TBI remain unclear. Our goal was to compare the clinical profile of older independently living veterans with and without prior TBI.

Setting

Two veterans' retirement communities.

Participants

Seventy-five participants with TBI and 71 without (mean age = 78 years).

Design

Cross-sectional.

Main measures

TBI history was determined by the Ohio State University TBI Questionnaire. We assessed psychiatric and medical history via interviews and chart review and conducted measures assessing functional/lifestyle, psychiatric, and cognitive outcomes. Regression analyses (adjusted for demographics, diabetes, prior depression, substance abuse, and site) were performed to compare between TBI and non-TBI participants.

Results

Compared with veterans without TBI, those with TBI had greater functional impairment (adjusted P = .05), endorsed more current depressive (adjusted P = .04) and posttraumatic stress disorder symptoms (adjusted P = .01), and had higher rates of prior depression and substance abuse (both adjusted Ps < .01). While composite memory and language scores did not differ between groups, participants with TBI performed worse on tests of executive functioning/processing speed (adjusted P = .01).

Conclusions

Our results suggest that TBI may have adverse long-term neurobehavioral consequences and that TBI-exposed adults may require careful screening and follow-up.

Background

Traumatic brain injury (TBI) has been identified as a risk factor for Parkinson's disease (PD). Motor dysfunction among TBI-exposed elders without PD has not been well characterized. We sought to determine whether remote TBI is a risk factor for motor dysfunction on exam and functionally relevant motor dysfunction in day-to-day life among independently living elders without PD.

Methods

This is a cross-sectional cohort study of independently living retired military veterans aged 50 or older with (n = 78) and without (n = 85) prior TBI-all without diagnosed PD. To characterize multidimensional aspects of motor function on exam, the Unified Parkinson's Disease Rating Scale (UPDRS) Motor Examination was performed by a board-certified neurologist and used to calculate a modified UPDRS (mUPDRS) global motor score and four domain scores (tremor, rigidity, bradykinesia, and posture/gait). Functionally relevant motor dysfunction was assessed via self-report of falls within the past year.

Results

In analyses adjusted for demographics and comorbidities that differed between groups, compared with veterans without TBI, those with moderate-to-severe TBI were more likely to have fallen in past year (33% vs. 14%, risk ratio 2.5 [95% confidence interval 1.1-5.4]), had higher (worse) mUPDRS global motor (p = .03) and posture/gait scores (p = .02), but not higher tremor (p = .70), rigidity (p = .21), or bradykinesia scores (p = .22). Mild TBI was not associated with worse motor function.

Conclusions

Remote moderate-to-severe TBI is a risk factor for motor dysfunction-defined as recent falls and impaired posture/gait-among older veterans. TBI-exposed older adults may be ideal candidates for aggressive fall-screening and prevention strategies.

To identify long-term effects of traumatic brain injury (TBI) on levels of plasma neuron-derived exosome (NDE) protein biomarkers of cognitive impairment (CI), plasmas were obtained from four groups of older veterans, who were matched for age and sex: no TBI or CI (n = 42), no TBI with CI (n = 19), TBI without CI (n = 21), and TBI with CI (n = 26). The TBI was sustained 12 to 74 years before the study in 75%. The NDEs were enriched by sequential precipitation and anti-L1CAM antibody immunoabsorption, and extracted protein biomarkers were quantified by enzyme-linked immunosorbent assays. Chronic NDE biomarkers known to increase for three to 12 months after TBI, including cellular prion protein (PrPc), synaptogyrin-3, P-T181-tau, P-S396-tau, Aβ42, and interleukin (IL)-6, were elevated significantly in subjects who had TBI and CI compared with controls with TBI but no CI. Chronic NDE biomarker levels in subjects without TBI showed significantly higher levels of PrPc, synaptogyrin-3, P-T181-tau, and Aβ42, but not P-S396-tau and IL-6, in those with CI compared with controls without CI. The acute NDE biomarkers claudin-5, annexin VII, and aquaporin-4 were not increased in either group with CI. The NDE biomarkers P-S396-tau and IL-6, which are increased distinctively with CI after TBI, may prove useful in evaluating CI in older patients. Aβ42 and P-tau species, as well as their respective putative receptors, PrPc and synaptogyrin-3, remain elevated for decades after TBI and may mediate TBI-associated CI and be useful targets for development of drugs.

Objective

To determine the prevalence and types of cognitive impairment in a sample of nondemented participants aged ≥90 (the oldest-old) and to examine the relationships between cognitive impairment and cardiovascular risk factors.

Participants

The participants were 420 nondemented individuals from The 90+ Study, a study of aging and dementia in the oldest-old. These participants were categorized into four nonoverlapping groups: normal cognition, amnestic mild cognitive impairment (aMCI), nonamnestic MCI (naMCI), and other cognitive impairment (OCI). History of cardiovascular risk factors was assessed through self-report.

Results

The overall prevalence of cognitive impairment in nondemented participants was 34.0% (95% CI: 29.5-38.5). The prevalence of OCI was highest (17.4%; 95% CI: 13.9-21.4), followed by aMCI (8.3%; 95% CI: 5.9-11.4) and naMCI (8.3%; 95% CI: 5.9-11.4). Normal cognition was present in 66.0% (95% CI: 61.2-70.5) of participants. History of hypertension and stroke were the only risk factors that varied between the groups, occurring more frequently in participants with naMCI (χ(2) = 3.82; P < .05) and OCI (χ(2) = 5.51; P < .05).

Conclusions

This study found a high prevalence of cognitive impairment in a sample of nondemented oldest-old. We did not find a strong relationship between cardiovascular risk factors and the cognitive impairment groups, other than between hypertension and naMCI and stroke and OCI. Future studies comparing the incidence of dementia in these groups will ultimately determine their predictive utility in the oldest-old.

Objective

To utilize a panel of 11 single chain variable fragments (scFvs) that selectively bind disease-related variants of TAR DNA-binding protein (TDP)-43, β-amyloid, tau, and α-synuclein to assess damage following traumatic brain injury (TBI), and determine if the presence of protein variants could account for the increased risk of various neurodegenerative diseases following TBI.

Methods

We utilized the panel of 11 scFvs in a sensitive ELISA format to analyze sera from 43 older veterans, 25 who had experienced at least 1 TBI incident during their lifetime (∼29.4 years after TBI), and 18 controls who did not incur TBI, in a cross-sectional study.

Results

Each of the 11 scFvs individually could significantly distinguish between TBI and control samples, though they did not detect each TBI sample. Comparing the levels of all 11 variants, all 25 TBI cases displayed higher reactivity compared to the controls and receiver operating characteristic analysis revealed 100% sensitivity and specificity. Higher total protein variants levels correlated with TBI severity and with loss of consciousness. Oligomeric tau levels distinguished between single and multiple TBI incidents. While all TBI cases were readily selected with the panel, the binding pattern varied from patient to patient, suggesting subgroups that are at increased risk for different neurodegenerative diseases.

Conclusion

The panel of protein variants-specific scFvs can be used to identify blood-based biomarkers indicative of TBI even 20 years or more after the initial TBI. Being able to identify subgroups of biomarker profiles allows for the possibility of individually targeted treatments.