Multifactorial mechanisms underlying late-onset Alzheimer's disease (LOAD) are poorly characterized from an integrative perspective. Here spatiotemporal alterations in brain amyloid-β deposition, metabolism, vascular, functional activity at rest, structural properties, cognitive integrity and peripheral proteins levels are characterized in relation to LOAD progression. We analyse over 7,700 brain images and tens of plasma and cerebrospinal fluid biomarkers from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Through a multifactorial data-driven analysis, we obtain dynamic LOAD–abnormality indices for all biomarkers, and a tentative temporal ordering of disease progression. Imaging results suggest that intra-brain vascular dysregulation is an early pathological event during disease development. Cognitive decline is noticeable from initial LOAD stages, suggesting early memory deficit associated with the primary disease factors. High abnormality levels are also observed for specific proteins associated with the vascular system's integrity. Although still subjected to the sensitivity of the algorithms and biomarkers employed, our results might contribute to the development of preventive therapeutic interventions.
Article abstract-Objective: To compare the incidence rates for AD among elderly African-American, Caribbean Hispanic, and white individuals and to determine whether coincident cerebrovascular disease contributes to the inconsistency in reported differences among ethnic groups. Methods: This was a population-based, longitudinal study over a 7-year period in the Washington Heights and Inwood communities of New York City. Annual incidence rates for AD were calculated and compared by ethnic group, and cumulative incidence adjusted for differences in education, diabetes, cardiovascular risk factors, and stroke was calculated. Results: The age-specific incidence rate for probable and possible AD was 1.3% (95% CI, 0.8 to 1.7) per person-year between the ages of 65 and 74 years, 4.0% (95% CI, 3.2 to 4.8) per person-year between ages 75 and 84 years, and 7.9% (95% CI, 5.5 to 10.5) per person-year for ages 85 and older. Compared to white individuals, the cumulative incidence of AD to age 90 years was increased twofold among African-American and Caribbean Hispanic individuals. Adjustment for differences in number of years of education, illiteracy, or a history of stroke, hypertension, heart disease, or diabetes did not change the disproportionate risks among the three ethnic groups. Conclusion: The incidence rate for AD was significantly higher among African-American and Caribbean Hispanic elderly individuals compared white individuals. The presence of clinically apparent cardiovascular or cerebrovascular disease did not contribute to the increased risk of disease. Because the proportion of African-American and Caribbean Hispanic individuals reaching ages 65 and older in the United States is increasing more rapidly than the proportion of white individuals, it is imperative that this disparity in health among the elderly be understood. NEUROLOGY 2001;56:49 -56 Prevalence and incidence rates for AD have been studied extensively throughout the world.1-20 Despite methodologic differences in these studies, most have shown a consistent rise in the frequency of AD with increasing age. Women appear to have a higher frequency of AD than men in some, but not all studies. 17,19,[21][22][23] Although the prevalence and incidence rates for dementia in Asia, China, Europe, and the United States are comparable, the types of dementia can vary. For example, the frequency of vascular dementia is reported to be higher than that of AD among East Asians 13 and JapaneseAmericans 18 compared with most populations in the United States and Europe.Only a few studies in the United States have compared the frequency of AD or other forms of dementia among major ethnic groups. No differences in the prevalence and incidence rates of AD were reported among African-American and white individuals in the Piedmont area of North Carolina participating in the Duke Established Populations for Epidemiologic Studies of the Elderly.5 However, Gurland et al. 8 reported a higher prevalence of all types of dementia, including AD, among African-American and Hispani...
Mild cognitively impaired patients with memory plus other cognitive domain deficits, rather than those with pure amnestic MCI, constituted the high-risk group. Deficits in verbal memory and psychomotor speed/executive function abilities strongly predicted conversion to AD.
Summary: Purpose: To determine cumulative incidence and predictors of new-onset seizures in mild Alzheimer's disease (AD) with a cohort followed prospectively. Limited information is available on the incidence of seizures, and no reports exist of seizure predictors in AD patients.Methods: Mild AD patients were prospectively followed at 6-month intervals to estimate incidence of unprovoked seizures, compare age-specific risk of unprovoked seizures with population norms, and identify characteristics at baseline (demographics, duration and severity of AD, physical and diagnostic test findings, and comorbid medical and psychiatric conditions) influencing unprovoked seizure risk. Review of study charts and medical records supplemented coded end-point data.Results: The cumulative incidence of unprovoked seizures at 7 years was nearly 8%. In all age groups, risk was increased compared with a standard population, with an 87-fold increase in the youngest group (age 50-59 years) and more than a threefold increase in the oldest group (age 85+ years). In multivariate modeling, independent predictors of unprovoked seizures were younger age [relative risk (RR), 0.89 per year increase in age; 95% confidence interval (CI), 0.82-0.97], African-American ethnic background (RR, 7.35; 95% CI, 1.42-37.98), more-severe dementia (RR, 4.15; 95% CI,, and focal epileptiform findings on electroencephalogram (EEG) (RR, 73.36; 95% CI, 1.75-3075.25).Conclusions: Seizure incidence is increased in people starting with mild-to-moderate AD. Younger individuals, African Americans, and those with more-severe disease or focal epileptiform findings on EEG were more likely to have unprovoked seizures.
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