Systematic Multi-Domain Alzheimer's Risk Reduction Trial (SMARRT): Study Protocol.

This article describes the protocol for the Systematic Multi-domain Alzheimer's Risk Reduction Trial (SMARRT), a single-blind randomized pilot trial to test a personalized, pragmatic, multi-domain Alzheimer's disease (AD) risk reduction intervention in a US integrated healthcare delivery system. Study participants will be 200 higher-risk older adults (age 70-89 years with subjective cognitive complaints, low normal performance on cognitive screen, and ≥ two modifiable risk factors targeted by our intervention) who will be recruited from selected primary care clinics of Kaiser Permanente Washington, oversampling people with non-white race or Hispanic ethnicity. Study participants will be randomly assigned to a two-year Alzheimer's risk reduction intervention (SMARRT) or a Health Education (HE) control. Randomization will be stratified by clinic, race/ethnicity (non-Hispanic white versus non-white or Hispanic), and age (70-79, 80-89). Participants randomized to the SMARRT group will work with a behavioral coach and nurse to develop a personalized plan related to their risk factors (poorly controlled hypertension, diabetes with evidence of hyper or hypoglycemia, depressive symptoms, poor sleep quality, contraindicated medications, physical inactivity, low cognitive stimulation, social isolation, poor diet, smoking). Participants in the HE control group will be mailed general health education information about these risk factors for AD. The primary outcome is two-year cognitive change on a cognitive test composite score. Secondary outcomes include: 1) improvement in targeted risk factors, 2) individual cognitive domain composite scores, 3) physical performance, 4) functional ability, 5) quality of life, and 6) incidence of mild cognitive impairment, AD, and dementia. Primary and secondary outcomes will be assessed in both groups at baseline and 6, 12, 18, and 24 months

Cognitive impairment in non-1 demented oldest-old: Prevalence and relationship to cardiovascular risk factors

ObjectiveTo determine the prevalence and types of cognitive impairment in a sample of non-demented aged 90 and older (the oldest-old) and to examine the relationships between cognitive impairment and cardiovascular risk factors.Participants420 non-demented participants from The 90+ Study, a study of aging and dementia in the oldest-old. Participants were categorized into four non-overlapping groups: normal cognition, amnestic mild cognitive impairment (aMCI), non-amnestic MCI (naMCI), and other cognitive impairment (OCI). History of cardiovascular risk factors was assessed through self-report.ResultsThe overall prevalence of cognitive impairment in non-demented 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 (χ2=3.82; p<0.05) and OCI (χ2=5.51; p<0.05).ConclusionsThis study found a high prevalence of cognitive impairment in a sample of non-demented 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

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

: To measure the incidence of disability in individuals aged 90 years and older and examine factors that may increase risk of disability.: The 90+ Study, a longitudinal study of aging, initiated in January 2003 with follow-up through May 2009.: A total of 216 nondisabled, prospectively followed participants who were aged 90 years or older at baseline.: 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.: 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.: 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.

ObjectiveTo examine the incidence of dementia among the oldest-old people with normal cognition and different types of cognitive impairment.MethodsThis 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).ResultsDementia 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.ConclusionsThe 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

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

ObjectiveTo examine the incidence of dementia among the oldest-old people with normal cognition and different types of cognitive impairment.MethodsThis 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).ResultsDementia 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.ConclusionsThe 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

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

ObjectiveTo 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.ParticipantsThe 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.ResultsThe 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).ConclusionsThis 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

Neuron-Derived Plasma Exosome Proteins after Remote Traumatic Brain Injury

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