2016 Alzheimer's disease facts and figures

This report provides information to increase understanding of the public health impact of Alzheimer's disease (AD), including incidence and prevalence, mortality rates, health expenditures and costs of care, and effect on caregivers and society in general. It also explores the roles and unique challenges of long‐distance caregivers, as well as interventions that target those challenges. An estimated 5.2 million Americans have AD. Approximately 200,000 people younger than 65 years with AD comprise the younger onset AD population; 5 million comprise the older onset AD population. Throughout the coming decades, the baby boom generation is projected to add about 10 million to the total number of people in the United States with AD. Today, someone in America develops AD every 68 seconds. By 2050, one new case of AD is expected to develop every 33 seconds, or nearly a million new cases per year, and the total estimated prevalence is expected to be 13.8 million. AD is the sixth leading cause of death in the United States and the fifth leading cause of death in Americans age 65 years or older. Between 2000 and 2010, the proportion of deaths resulting from heart disease, stroke, and prostate cancer decreased 16%, 23%, and 8%, respectively, whereas the proportion resulting from AD increased 68%. The number of deaths from AD as determined by official death certificates (83,494 in 2010) likely underrepresents the number of AD‐related deaths in the United States. A projected 450,000 older Americans with AD will die in 2013, and a large proportion will die as a result of complications of AD. In 2012, more than 15 million family members and other unpaid caregivers provided an estimated 17.5 billion hours of care to people with AD and other dementias, a contribution valued at more than $216 billion. Medicare payments for services to beneficiaries age 65 years and older with AD and other dementias are three times as great as payments for beneficiaries without these conditions, and Medicaid payments are 19 times as great. Total payments in 2013 for health care, long‐term care, and hospice services for people age 65 years and older with dementia are expected to be $203 billion (not including the contributions of unpaid caregivers). An estimated 2.3 million caregivers of people with AD and other dementias live at least 1 hour away from the care recipient. These “long‐distance caregivers” face unique challenges, including difficulty in assessing the care recipient's true health condition and needs, high rates of family disagreement regarding caregiving decisions, and high out‐of‐pocket expenses for costs related to caregiving. Out‐of‐pocket costs for long‐distance caregivers are almost twice as high as for local caregivers.

2013 Alzheimer's disease facts and figures

Background and Purpose—This scientific statement provides an overview of the evidence on vascular contributions to cognitive impairment and dementia. Vascular contributions to cognitive impairment ...

Vascular Contributions to Cognitive Impairment and Dementia A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association

In the past 8 years, both the International Working Group (IWG) and the US National Institute on Aging-Alzheimer's Association have contributed criteria for the diagnosis of Alzheimer's disease (AD) that better define clinical phenotypes and integrate biomarkers into the diagnostic process, covering the full staging of the disease. This Position Paper considers the strengths and limitations of the IWG research diagnostic criteria and proposes advances to improve the diagnostic framework. On the basis of these refinements, the diagnosis of AD can be simplified, requiring the presence of an appropriate clinical AD phenotype (typical or atypical) and a pathophysiological biomarker consistent with the presence of Alzheimer's pathology. We propose that downstream topographical biomarkers of the disease, such as volumetric MRI and fluorodeoxyglucose PET, might better serve in the measurement and monitoring of the course of disease. This paper also elaborates on the specific diagnostic criteria for atypical forms of AD, for mixed AD, and for the preclinical states of AD.

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Advancing research diagnostic criteria for Alzheimer's disease: the IWG-2 criteria

Apolipoprotein E (Apo-E) is a major cholesterol carrier that supports lipid transport and injury repair in the brain. APOE polymorphic alleles are the main genetic determinants of Alzheimer disease (AD) risk: individuals carrying the e4 allele are at increased risk of AD compared with those carrying the more common e3 allele, whereas the e2 allele decreases risk. Presence of the APOE e4 allele is also associated with increased risk of cerebral amyloid angiopathy and age-related cognitive decline during normal ageing. Apo-E-lipoproteins bind to several cell-surface receptors to deliver lipids, and also to hydrophobic amyloid-β (Aβ) peptide, which is thought to initiate toxic events that lead to synaptic dysfunction and neurodegeneration in AD. Apo-E isoforms differentially regulate Aβ aggregation and clearance in the brain, and have distinct functions in regulating brain lipid transport, glucose metabolism, neuronal signalling, neuroinflammation, and mitochondrial function. In this Review, we describe current knowledge on Apo-E in the CNS, with a particular emphasis on the clinical and pathological features associated with carriers of different Apo-E isoforms. We also discuss Aβ-dependent and Aβ-independent mechanisms that link Apo-E4 status with AD risk, and consider how to design effective strategies for AD therapy by targeting Apo-E.

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Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy

Neuropathological evaluation of mixed dementia

The prevalence of Alzheimer disease (AD) and vascular dementia (VD) increases with advancing age, but less so after age 90 years. A retrospective hospital-based study of the relative prevalence of different disorders was performed in 1,110 consecutive autopsy cases of demented elderly in Vienna, Austria (66% females, MMSE <20; mean age 83.3 +/- 5.4 SD years). It assessed clinical, general autopsy data and neuropathology including immunohistochemistry. Neuropathologic diagnosis followed current consensus criteria. Four age groups (7-10th decade) were evaluated. In the total cohort AD pathology was seen in 82.9% ("pure" AD 42.9%; AD + other pathologies 39.9%), VD in 10.8% (mixed dementia, MIX, i.e. AD + vascular encephalopathy in 5.5%); other disorders in 5.7%, and negative pathology in 0.8%. The relative prevalence of AD increased from age 60 to 89 years and decreased slightly after age 90+, while "pure" VD diagnosed in the presence of vascular encephalopathy of different types with low neuritic AD pathology (Braak stages <3; mean 1.2-1.6) decreased progressively from age 60 to 90+; 85-95% of these patients had histories of diabetes, morphologic signs of hypertension, 65% myocardial infarction/cardiac decompensation, and 75% a history of stroke(s). Morphologic subtypes, subcortical arteriosclerotic (the most frequent), multi-infarct encephalopathy, and strategic infarct dementia showed no age-related differences. The relative prevalence of AD + Lewy pathology remained fairly constant with increasing age. Mixed dementia and AD with minor cerebrovascular lesions increased significantly with age, while other dementias decreased. This retrospective study using strict morphologic criteria confirmed increased prevalence of AD with age, but mild decline at age 90+, and progressive decline of VD, while AD + vascular pathologies including MIX showed considerable age-related increase, confirming that mixed pathologies account for most dementia cases in very old persons. A prospective clinicopathologic study in oldest-old subjects showed a significant increase in both AD and cerebral amyloid angiopathy (CAA), but decrease in VD over age 85, while in a small group of old subjects CAA without considerable AD pathology may be an independent risk factor for cognitive decline.

Prevalence of dementia disorders in the oldest-old: an autopsy study

Clinicopathological analysis of dementia disorders in the elderly

The unequivocal diagnosis of Alzheimer’s disease (AD) rests on histopathological evidence at brain autopsy or biopsy. The morphology of AD includes cerebral atrophy, deposition of βA4 amyloid (Aβ) (senile plaques and amyloid angiopathy), neuritic changes (neuritic plaques, neurofibrillary tangles (NFT) and neuropil threads) with formation of paired helical filaments (PHF) containing polymerized hyperphosphorylated tau protein triplet, causing disruption of the neuronal cytoskeleton with loss of synapses and neurons, with altered cortico-cortical connectivity, leading to disconnection of the cerebral cortex. Defining criteria for the morphologic diagnosis of AD is difficult due to the phenotypic heterogeneity of the disease, the absence of specific markers, and overlap of AD morphology with that observed in non-demented elderly individuals. This gray zone between normal to pathologic aging and full-fledged AD represents an important diagnostic problem and should be overcome by better standardized criteria that will allow to minimize interrater and interlaboratory variability in the diagnosis of AD. Current criteria for the morphologic diagnosis of AD are based on (semi)quantitative assessment of diffuse and neuritic plaques (NIA), exclusively neuritic plaques (CERAD), plaques and NFT in neocortex and hippocampus (Tierney et al., 1988), and staging of hierarchic spreading of neuritic AD changes (Braak and Braak, 1991); all of them have weaknesses and need to be revalidated. Multivariant analysis of an autopsy series of elderly subjects revealed significant correlations between psychostatus and both the CERAD criteria and Braak staging. Recent recommendations of the NIA-Reagan Institute for the morphologic diagnosis of AD are presented. Although the role of plaques and NFT in the pathogenesis of AD remains undetermined, clinicopathological correlative studies have shown that both lesions, if present in sufficient numbers, particularly in the neocortex, are considered the best morphological signposts for AD. Recent studies on neuron death in AD that, at least in part, appears different from classical apoptosis and may precede the symptomatic stage of AD, have shown varying results indicating only indirect relationship between DNA fragmentation and both Aβ deposition and NFTs. Both these AD-typical markers appear to increase the risk of cells to degenerate, but are not the sole responsibles of the degenerative process in AD, the basic mechanisms of which remain to be elucidated.

Neuropathology of Alzheimer's disease: a critical update.

The prevalence, morphology and pathogenesis of vascular dementia (VaD), recently termed vascular cognitive impairment, are a matter of discussion, and currently used clinical diagnostic criteria show moderate sensitivity (average 50%) and variable specificity (range 64–98%). In Western clinic-based series, VaD is suggested in 8–10% of cognitively impaired aged subjects. Its prevalence in autopsy series varies from 0.03 to 58%, with reasonable values of 8–15%, while in Japan it is seen in 22–35%. Neuropathologic changes associated with cognitive impairment include multifocal and/or diffuse disease and focal lesions: multi-infarct encephalopathy, white matter lesions or arteriosclerotic subcortical (leuko)encephalopathy, multilacunar state, mixed cortico-subcortical type, borderline/watershed lesions, rare granular cortical atrophy, post-ischemic encephalopathy and hippocampal sclerosis. They result from systemic, cardiac and local large or small vessel disease. Recent data indicate that cognitive decline is commonly associated with widespread small ischemic/vascular lesions (microinfarcts, lacunes) throughout the brain with predominant involvement of subcortical and functionally important brain areas. Their pathogenesis is multifactorial, and their pathophysiology affects neuronal networks involved in cognition, memory, behavior and executive functioning. Vascular lesions often coexist with Alzheimer disease (AD) and other pathologies. Minor cerebrovascular lesions, except for severe amyloid angiopathy, appear not essential for cognitive decline in full-blown AD, while both mild Alzheimer pathology and small vessel disease may interact synergistically. The lesion pattern of “pure” VaD, related to arteriosclerosis and microangiopathies, differs from that in mixed-type dementia (AD with vascular encephalopathy), more often showing large infarcts, which suggests different pathogenesis of both types of lesions. Due to the high variability of cerebrovascular pathology and its causative factors, no validated neuropathologic criteria for VaD are available, and a large variability across laboratories still exists in the procedures for morphologic examination and histology techniques.

Kurt A. Jellinger

Papers

Neuropathological evaluation of mixed dementia

Prevalence of dementia disorders in the oldest-old: an autopsy study

Clinicopathological analysis of dementia disorders in the elderly

Neuropathology of Alzheimer's disease: a critical update.

The enigma of vascular cognitive disorder and vascular dementia