Epidemiology of Alzheimer disease

Abstract

The global prevalence of dementia is estimated to be as high as 24 million, and is predicted to double every 20 years through to 2040, leading to a costly burden of disease. Alzheimer disease (AD) is the leading cause of dementia and is characterized by a progressive decline in cognitive function, which typically begins with deterioration in memory. Before death, individuals with this disorder have usually become dependent on caregivers. The neuropathological hallmarks of the AD brain are diffuse and neuritic extracellular amyloid plaques-which are frequently surrounded by dystrophic neurites-and intracellular neurofibrillary tangles. These hallmark pathologies are often accompanied by the presence of reactive microgliosis and the loss of neurons, white matter and synapses. The etiological mechanisms underlying the neuropathological changes in AD remain unclear, but are probably affected by both environmental and genetic factors. Here, we provide an overview of the criteria used in the diagnosis of AD, highlighting how this disease is related to, but distinct from, normal aging. We also summarize current information relating to AD prevalence, incidence and risk factors, and review the biomarkers that may be used for risk assessment and in diagnosis.

Figure 1

Potential mechanisms linking vascular risk factors and cognitive impairment. At least two pathways exist that result in cognitive impairment and dementia: development of cerebrovascular disease may lead to vascular cognitive impairment syndromes, and deposition of amyloid-β may lead to other distinct amnestic clinical syndromes, including Alzheimer disease. In addition, these pathways may overlap and interact, resulting in mixed cognitive syndromes.

Figure 2

T1-weighted MRI scan of a patient with a clinical diagnosis of late-onset AD. As is typical for late-onset AD, the MRI scan shows generalized brain atrophy and loss of gray matter affecting the hippocampus (red arrow), entorhinal cortex (green arrow) and perirhinal cortex (blue arrow). Abbreviation: AD, Alzheimer disease.

Figure 3

Changes revealed by PET in the AD brain. a | ¹⁸F-FDG-PET patterns characteristic of metabolic activity in cognitively normal individuals and patients with late-onset AD. In comparison with people aging normally, individuals with late-onset AD show decreased bilateral glucose metabolism, particularly in the temporal and parietal regions. b | ¹¹C-PIB PET images characteristic of elderly individuals without cognitive impairment and patients with late-onset AD. The high concentrations of ¹¹C-PIB in the AD brain are suggestive of high amounts of amyloid deposits. Abbreviations: AD, Alzheimer disease; FDG, 2-fluoro-2-deoxy-d-glucose; PIB, Pittsburgh compound B.