Cardiovascular Risk Factors and Risk of Alzheimer Disease and Mortality: A Latent Class Approach

BackgroundCardiovascular risk factors co‐occur with one another, and little is known about the extent of their clustering and risk of Alzheimer disease (AD). We identify groups of cardiovascular risk factors in cognitively normal individuals and investigate between‐group differences in incident AD and death.Methods and ResultsCognitively normal individuals were recruited from the National Alzheimer's Coordinator Center. A latent class analysis was conducted with hypertension, hypercholesterolemia, heart condition, stroke, smoking history, diabetes, and high body mass index. Between‐group differences in the incidence of AD, mortality, and mortality‐adjusted AD were investigated. This study included 12 412 cognitively normal individuals (average follow‐up, 65 months). Three groups were identified: (1) low probabilities of cardiovascular risk factors (reference; N=5398 [43%]), (2) hypertension and hypercholesterolemia (vascular‐dominant; N=5721 [46%]), and (3) hypertension, hypercholesterolemia, diabetes, and high body mass index (vascular‐metabolic; N=1293 [10%]). Both vascular groups were significantly older, had more men, were slightly less educated, and were slightly more cognitively impaired than the reference group (all P<0.05). However, only the vascular‐metabolic group had a significantly younger age of death compared with the reference group (84.3 versus 88.7 years, P<0.001). Only the vascular‐dominant group had a greater incidence of AD (odds ratio [OR], 1.30; P<0.001) compared with the reference group. Mortality was greater in the vascular‐dominant (OR, 3.26; P<0.001) and vascular‐metabolic groups (OR, 1.84; P=0.02). Mortality‐adjusted AD was greater in the vascular‐dominant (OR, 1.54; P=0.02) and vascular‐metabolic groups (OR, 1.46; P=0.04).ConclusionsThree distinct cardiovascular risk factor groups were identified in cognitively normal elderly individuals. Only the vascular‐dominant group was associated with a greater incidence of AD. Selective mortality may contribute to the attenuated association between the vascular‐metabolic group and incident AD.publishedVersio

Biomarkers of Agitation in Patients with Alzheimer's disease

Agitation is challenging to treat in Alzheimer’s disease (AD) and has significant implications for patients and caregivers. A major source of difficulty in identifying safe and effective treatments for agitation is the lack of validated biomarkers. The goal of this work was to investigate biomarkers of agitation in patients with AD. Study 1: This study systematically reviewed 57 papers investigating biomarkers of agitation in AD. Studies 2-5: Blood samples were collected from 38 participants enrolled in a randomized, placebo-controlled trial investigating nabilone, a synthetic cannabinoid, for the treatment of agitation in AD. The cross-sectional and longitudinal associations between agitation and 24-S-hydroxycholesterol (cerebrocholesterol (Cchol) (study 2), lipid peroxidation markers of oxidative stress (OS) (study 3), and inflammatory cytokines (study 4) and a biosignature of response to nabilone (study 5) were investigated. These processes are altered in AD and may be associated with agitation and/or endocannabinoid signalling. Study 1: Of six classes of biomarkers identified, most were diagnostic in nature, substantiating the need for studies investigating the longitudinal associations between biomarkers and agitation in AD. Study 2: Cchol was associated with agitation severity cross-sectionally, and longitudinally. However, Cchol did not predict response to nabilone, and did not change over time with nabilone. Study 3: Baseline levels of the late-stage lipid-peroxidation marker, 4-hydroxynonenal (4-HNE) were associated with agitation severity cross-sectionally, and longitudinally. However changes in 4-HNE were not associated with changes in agitation severity in either phase. Study 4: The pro-inflammatory cytokine, tumor necrosis factor-alpha (TNF-α) was associated with agitation severity cross-sectionally. Lower baseline and decreases in TNF-α were associated with decreases in agitation severity in the nabilone phase only. Study 5: Inflammatory cytokines, and markers of OS predicted response to nabilone based on symptoms of verbal and physical agitation, respectively. Findings from the nabilone trial suggest that Cchol, 4-HNE and TNF-α may be useful markers of agitation severity. Additionally, response to nabilone may be influenced by the degree of OS and neuroinflammation a patient may have. As there are no validated biomarkers of agitation, identifying markers of agitation and response would assist in identifying patients who may benefit from treatment with nabilone.Ph.D

Use of Physical and Intellectual Activities and Socialization in the Management of Cognitive Decline of Aging and in Dementia: A Review

Lifestyle nonpharmacological interventions can have a deep effect on cognitive aging. We have reviewed the available literature on the effectiveness of physical activity, intellectual stimulation, and socialization on the incidence of dementia and on the course of dementia itself. Even though physical activity appears to be beneficial in both delaying dementia onset and in the course of the disease, more research is needed before intellectual stimulation and socialization can be considered as treatments and prevention of the disease. Through our paper, we found that all three nonpharmacological treatments provide benefits to cognition and overall well-being in patients with age-related cognitive impairments. These interventions may be beneficial in the management of dementia