2016 Alzheimer's disease facts and figures

Background The Religious Orders Study and Rush Memory and Aging Project are both ongoing longitudinal clinical-pathologic cohort studies of aging and Alzheimer's disease (AD). Objectives To summarize progress over the past five years and its implications for understanding neurodegenerative diseases. Methods Participants in both studies are older adults who enroll without dementia and agree to detailed longitudinal clinical evaluations and organ donation. The last review summarized findings through the end of 2011. Here we summarize progress and study findings over the past five years and discuss new directions for how these studies can inform on aging and AD in the future. Results We summarize 1) findings on the relation of neurobiology to clinical AD; 2) neurobiologic pathways linking risk factors to clinical AD; 3) non-cognitive AD phenotypes including motor function and decision making; 4) the development of a novel drug discovery platform. Conclusion Complexity at multiple levels needs to be understood and overcome to develop effective treatments and preventions for cognitive decline and AD dementia.

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Religious Orders Study and Rush Memory and Aging Project.

Suffering related to dementia is multifaceted because cognitive and physical functioning slowly deteriorates. Advanced age and sex, two of the most prominent risk factors for dementia, are not modifiable. Lifestyle factors such as smoking, excessive alcohol use, and poor diet modulate susceptibility to dementia in both males and females. The degree to which the resulting health conditions (eg, obesity, type 2 diabetes, and cardiovascular disease) impact dementia risk varies by sex. Depending on the subtype of dementia, the ratio of male to female prevalence differs. For example, females are at greater risk of developing Alzheimer disease dementia, whereas males are at greater risk of developing vascular dementia. This review examines sex and gender differences in the development of dementia with the goal of highlighting factors that require further investigation. Considering sex as a biological variable in dementia research promises to advance our understanding of the pathophysiology and treatment of these conditions.

Considering sex and gender in Alzheimer disease and other dementias

Adverse experiences in childhood and adolescence, defined as subjectively perceived threats to the safety or security of the child’s bodily integrity, family, or social structures, are known to be ...

Childhood and Adolescent Adversity and Cardiometabolic Outcomes: A Scientific Statement From the American Heart Association.

Alzheimer's disease (AD) is a neurodegenerative disease that is of high importance to the neuroscience world, yet the complex pathogenicity is not fully understood. Inflammation is usually observed in AD and could implicate both beneficial or detrimental effects depending on the severity of the disease. During initial AD pathology, microglia and astrocyte activation is beneficial since they are involved in amyloid-beta clearance. However, with the progression of the disease, activated microglia elicit detrimental effects by the overexpression of pro-inflammatory cytokines such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) bringing forth neurodegeneration in the surrounding brain regions. This results in decline in Aβ clearance by microglia; Aβ accumulation thus increases in the brain resulting in neuroinflammation. Thus, Aβ accumulation is the effect of increased release of pro-inflammatory molecules. Reactive astrocytes acquire gain of toxic function and exhibits neurotoxic effects with loss of neurotrophic functions. Astrocyte dysfunctioning results in increased release of cytokines and inflammatory mediators, neurodegeneration, decreased glutamate uptake, loss of neuronal synapses, and ultimately cognitive deficits in AD. We discuss the role of intracellular signaling pathways in the inflammatory responses produced by astrocytes and microglial activation, including the glycogen synthase kinase-3β, nuclear factor kappa B cascade, mitogen-activated protein kinase pathways and c-Jun N-terminal kinase. In this review, we describe the role of neuroinflammation in the chronicity of AD pathogenesis and an overview of the recent research towards the development of new therapies to treat this disorder.

https://link.springer.com/content/pdf/10.1007/s10787-019-00580-x

Activation of microglia and astrocytes: a roadway to neuroinflammation and Alzheimer's disease.

The study aim was to describe the temporal course of cognitive decline in Alzheimer‘s disease (AD). We selected 226 persons from 2 longitudinal clinical-pathological studies who were cognitively healthy at baseline, followed at least 4 years (mean = 10.2, SD = 3.5), and clinically diagnosed with AD at some point during follow-up. Each evaluation included a battery of 17 cognitive tests from which a previously established composite measure of global cognition was derived. In those who died, a uniform neuropathologic examination established the pathological diagnoses of Alzheimer's disease and other common conditions that impair cognition. Mixed-effects models with 2 change points were used to assess trajectories of cognitive decline. In the main analysis, there was no change in cognitive function until a mean of 7.5 years before dementia was diagnosed (95% confidence interval [CI]: -8.3, -6.7). The global cognitive measure declined a mean of 0.087-unit per year (95% CI: -0.099, -0.073) until a mean of 2.0 years before the diagnosis (95% CI: -2.2, -1.7) when it increased more than fourfold to a mean loss of 0.370-unit per year (95% CI: -0.417, -0.334). Of 126 individuals who died and underwent autopsy, 101 (80%) met pathologic criteria for AD of whom 67 had at least one other pathologic condition. Pathologic measures of AD and cerebral infarction were not strongly related to cognitive trajectories. The results indicate that cognitive decline in AD begins many years before dementia is diagnosed and accelerates during the course of the disease.

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The natural history of cognitive decline in Alzheimer's disease.

This study addressed the hypothesis that late life cognitive decline leads to loss of well-being. Participants are older persons from the Rush Memory and Aging Project. Beginning in 2001, they underwent annual clinical evaluations that included detailed cognitive performance testing and a 10-item self-report measure of purpose in life, an aspect of well-being. Initial analyses involved 1,049 individuals who were without dementia at baseline and followed a mean of 5.0 years. The intercepts and slopes of global cognition and purpose were positively correlated, and level of cognition at a given evaluation predicted level of purpose at the subsequent evaluation, consistent with the study hypothesis. Purpose also predicted subsequent cognition. These findings persisted in analyses that excluded mild cognitive impairment or controlled for time varying levels of depressive symptoms or disability. To see whether cognitive decline's correlation with purpose differed from its correlation with other aspects of well-being, we conducted additional analyses on a subgroup of 560 persons without dementia who completed a multidimensional measure of well-being once between 2008 and 2011. More rapid cognitive decline in the period preceding well-being assessment (M = 5.5 years, SD = 2.8) was associated with lower level of nearly all aspects of well-being (5 of 6 measures), but the extent of the association varied across well-being dimensions and was stronger for purpose than for self-acceptance and autonomy. The results support the hypothesis that cognitive aging leads to diminished well-being, particularly aspects such as purpose in life that involve behavioral regulation.

The influence of cognitive decline on well-being in old age.

Objective: The purpose of the study was to test the hypothesis that a higher level of childhood adversity is associated with increased risk of cerebral infarction in old age Methods: Older participants in a longitudinal clinical–pathologic study rated adverse childhood experiences (eg, emotional neglect, parental intimidation and violence) on a previously established 16-item scale During a mean of 35 years of follow-up, there were 257 deaths, with 206 brain autopsies (802) Number of chronic cerebral infarcts (gross plus microscopic; expressed as 0, 1, or >1) was determined in a uniform neuropathologic examination, which had been completed in 192 individuals at the time of these analyses Results: Childhood adversity scores ranged from 0 to 31 (mean = 83, SD = 64) In an ordinal logistic regression model adjusted for age, sex, and education, higher adversity was associated with higher likelihood of chronic cerebral infarction In analyses of childhood adversity subscales, only emotional neglect was associated with infarction (odds ratio [OR] = 1097; 95% confidence interval [CI] 1048–1148) The likelihood of infarction was 28 times higher (95% CI 20–41) in those reporting a moderately high level of childhood emotional neglect (score = 6, 75th percentile) vs a moderately low level of neglect (score = 1, 25th percentile) Results were comparable in subsequent analyses that controlled for lifetime socioeconomic status, cardiovascular risk factors, and an anxiety-related trait Conclusion: Emotional neglect in childhood may be a risk factor for cerebral infarction in old age

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Sophia E. Anagnos

Papers

The natural history of cognitive decline in Alzheimer's disease.

The influence of cognitive decline on well-being in old age.

Emotional neglect in childhood and cerebral infarction in older age