Carrie B. Peltz

Plasma phospholipids identify antecedent memory impairment in older adults

Alzheimers disease causes a progressive dementia that currently affects over 35 million individuals worldwide and is expected to affect 115 million by 2050 (ref. 1). There are no cures or disease-modifying therapies, and this may be due to our inability to detect the disease before it has progressed to produce evident memory loss and functional decline. Biomarkers of preclinical disease will be critical to the development of disease-modifying or even preventative therapies. Unfortunately, current biomarkers for early disease, including cerebrospinal fluid tau and amyloid-β levels, structural and functional magnetic resonance imaging and the recent use of brain amyloid imaging or inflammaging, are limited because they are either invasive, time-consuming or expensive. Blood-based biomarkers may be a more attractive option, but none can currently detect preclinical Alzheimers disease with the required sensitivity and specificity. Herein, we describe our lipidomic approach to detecting preclinical Alzheimers disease in a group of cognitively normal older adults. We discovered and validated a set of ten lipids from peripheral blood that predicted phenoconversion to either amnestic mild cognitive impairment or Alzheimers disease within a 2–3 year timeframe with over 90% accuracy. This biomarker panel, reflecting cell membrane integrity, may be sensitive to early neurodegeneration of preclinical Alzheimers disease.

Alzheimer disease pathology and longitudinal cognitive performance in the oldest-old with no dementia.

Objective: It has been hypothesized that individuals without dementia with Alzheimer disease (AD) neuropathology may be in the preclinical stages of dementia and could be experiencing subtle cognitive decline. The purpose of this study was to compare longitudinal cognitive performance in oldest-old individuals without dementia with and without AD neuropathology. Methods: The study included 58 individuals without dementia from The 90+ Autopsy Study, a population-based study of aging and dementia in individuals aged 90 and older. Participants had neurologic and neuropsychological testing every 6 months with an average of 3 years of follow-up. We compared the trajectory of cognitive performance on the Modified Mini-Mental State Examination (3MS) and the California Verbal Learning Test II (CVLT) by level of AD neuropathology. Based on Consortium to Establish a Registry for Alzheimers Disease plaque staging, individuals were categorized as having low (none or sparse) or high (moderate or frequent) plaques. Based on Braak and Braak staging, participants were classified as having low (stages I–III) or high (IV–VI) tangles. Results: No significant differences were found in 3MS or CVLT cognitive performance over time based on plaque or tangle staging. Both high and low pathology groups showed modest improvements on the 3MS and CVLT consistent with learning effects. Conclusions: AD neuropathology at autopsy is not associated with the trajectory of cognitive performance in the 3 years before death in oldest-old without dementia. Despite the presence of AD neuropathology at death, oldest-old without dementia display learning effects on cognitive tests. Further research is necessary to understand factors other than AD neuropathology that may affect cognition in the oldest-old.

Cognitive impairment in nondemented oldest-old: prevalence and relationship to cardiovascular risk factors.

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.

Disability in the oldest-old: incidence and risk factors in the 90+ study.

OBJECTIVES : To measure the incidence of disability in individuals aged 90 years and older and examine factors that may increase risk of disability. DESIGN AND SETTING : The 90+ Study, a longitudinal study of aging, initiated in January 2003 with follow-up through May 2009. PARTICIPANTS : A total of 216 nondisabled, prospectively followed participants who were aged 90 years or older at baseline. MEASUREMENTS : The incidence of disability was measured as needing help on one or more activities of daily living and calculated using person years. Risk factors were examined by using a Cox proportional hazards analysis. RESULTS : The overall incidence of disability was 16.4% per year (95% confidence interval: 13.3-20.0) and did not differ by gender. Disability incidence increased with age from 8.3% in the 90-94 age group to 25.7% in the 95 years and older age group. Several factors were associated with increased risk of disability, including history of congestive heart failure, depression, poor self-rated quality of life, and cognitive impairment. CONCLUSION : Disability incidence is high and increases rapidly with age in the oldest-old, with rates essentially tripling between ages 90-94 years and 95+ years. Some factors associated with increased risk of disability in younger elderly continue to be risk factors in the oldest-old. Because of the tremendous social and financial impact of disability and the rapid growth of the oldest-old, the development of strategies to delay disability in the elderly should be a priority for healthcare research.

Incidence of dementia in oldest-old with amnestic MCI and other cognitive impairments

Objective: To examine the incidence of dementia among the oldest-old people with normal cognition and different types of cognitive impairment. Methods: This study included 395 participants without dementia (mean age 93.3 years) from The 90+ Study, a prospective, population-based study of aging and dementia in people aged 90 years and older. The participants had evaluations for dementia every 6 months, and their average follow-up was 2.5 years. We examined the incidence of all-cause dementia in participants stratified into 4 cognitive groups: normal, amnestic mild cognitive impairment (aMCI), nonamnestic mild cognitive impairment (naMCI), and other cognitive impairment (OCI). Results: Dementia incidence was highest for participants with aMCI (31.4% per year) and OCI (39.9% per year). Participants with naMCI had an incidence of 14.1% per year, and participants with normal cognition had an incidence of 8.4% per year. Dementia incidence was associated with increasing age in both normal and cognitively impaired participants; however, an APOE4 allele was associated with a higher dementia incidence only in participants with baseline cognitive impairment. Conclusions: The risk of developing dementia in the oldest-old is high and increases to higher rates when cognitive impairment is present. Similar to results of studies in younger elderly individuals, cognitive impairment and increasing age were related to increased dementia incidence. High dementia incidence rates in the oldest-old individuals, particularly when cognitively impaired, emphasize the need to further study cognitive impairment and dementia in this rapidly expanding age group.

Long-term Cognitive Trajectories and Mortality in Older Women

BACKGROUND Few studies have examined whether change in cognition is linked to mortality. This study examined the relationship between cognitive trajectories in older age and risk of death. METHODS We studied community-dwelling, nondemented women aged 65+ (mean age = 71) enrolled in a prospective study of aging and followed up to 25 years. A modified Mini-Mental State Examination (mMMSE) and Trail Making Task Part B (TMTB) were administered at multiple visits during follow-up. We examined the association between cognitive trajectories (analyzed by quintiles) from baseline to age 80 (n = 7,477 for mMMSE and n = 6,503 for TMTB) and all-cause mortality after age 80 using Cox regression models, both unadjusted and adjusted for education, physical activity, alcohol, depression score, current smoking and history of hypertension and diabetes. Cause of death was determined from death certificates, classified as cardiovascular, cancer and other. RESULTS Women with greater rate of decline were older, less educated, less physically active, had higher depression score and were more likely to have a history of hypertension and diabetes (all p < .01). Participants with the greatest decline (quintile 1) had an increased risk of death (mMMSE hazard ratio [HR] = 1.28; TMTB HR = 1.43] and those with the least decline (quintile 5) had a decreased risk of death (mMMSE HR = 0.73; TMTB HR = 0.61) compared with intermediate decliners (quintiles 2-4). Cognitive trajectories were associated with cardiovascular mortality and other causes of death, but not cancer deaths. CONCLUSIONS Our study suggests that greater decline in general cognition or executive function is associated with higher rates of mortality in oldest-old women.

Abnormal EEGs in Cognitively and Physically Healthy Oldest-Old: Findings from The 90+ Study

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.

BATHING AS A POTENTIAL TARGET FOR DISABILITY REDUCTION IN THE OLDEST OLD

We know that functional disability increases with age, but the magnitude of specific limitations is still largely unknown in the oldest old (those aged 90 years or older). The 90+ Study, a population-based study of aging, examined disability in activities of daily living (ADLs; defined as bathing, dressing, feeding, toileting, walking, and transferring in and out of a bed or chair),1 in the oldest old, the fastest growing age group in the United States. By examining the incidence of individual ADL disability, The 90+ Study determined the ADLs for which the most individuals were impaired; in addition, it sought to determine which ADLs make the best targets for potential therapeutics. To determine incident disability in each ADL, participants in the study were asked to identify an informant who could best provide researchers with information about their functional abilities via postal mail. A questionnaire was mailed annually to this informant asking about the participants abilities for each ADL. We examined the incidence rates for each ADL using a person-years analysis. We defined disability in an ADL as requiring help from another person to perform it. At baseline, the mean age of the 216 nondisabled participants was 93.7 years; 56.9% still lived alone. Mean follow-up time was 2.7 years. The incidence of bathing disability was 14.9% per year (95% confidence interval[CI] = 12.0, 18.2), which was significantly higher than any other ADL (Figure 1). The ADL with the lowest incidence rate of disability was walking (6.9% per year, 95% CI = 5.2, 9.0). FIGURE 1 Incidence of problems with the activities of daily living among those aged 90 years or older: The 90+ Study. According to The 90+ Study, bathing is the ADL with the highest disability incidence in the oldest old. We are not the first to show that problems with bathing are especially detrimental to the elderly. Bathing is described as a “sentinel event in the disabling process,”2 and those unable to bathe themselves without help are more likely to need long-term care.3 In the United States, there are more than 22 million unpaid informal caregivers for seniors, a number that is projected to double over the next 30 years.4 Given that more than 51% of the oldest-old still require help from another person to bathe,5 caregivers will be most often assisting with bathing despite the fact that bathing assistive devices are the most frequently used assistive devices in the oldest-old.6 These current bathing assistive devices then appear to be ineffective at preventing dependency in the oldest-old. Developing effective assistive devices for bathing—like those available for walking—would likely have the greatest benefit in reducing caregiver need, and should be a focus of health care research. If these devices are effective, health care costs for the elderly may decline dramatically.

Remote Traumatic Brain Injury Is Associated with Motor Dysfunction in Older Military Veterans

Background Traumatic brain injury (TBI) has been identified as a risk factor for Parkinsons 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 Parkinsons 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.

BLOOD-BASED BIOMARKER PROFILE OF OLDER VETERANS WITH REMOTE TBI

not available. PL-05-02 AD BIOMARKER EPIDEMIOLOGY IN THE AGING POPULATION: PREVALENCE, RISK FACTORS, AND OUTCOMES Prashanthi Vemuri, Mayo Clinic, Rochester, MN, USA. Contact e-mail: vemuri.prashanthi@mayo.edu Abstract not available.not available.