Studies suggest that mixed dementia is the norm, and the number of distinct combinations of mixed dementia is extensive.34-35 Mixed dementia is especially common at advanced ages.28,36 For example, the oldest-old, those age 85 or older, are more likely than those younger than 85 to have evidence of two or more causes of dementia.26-27 Having Alzheimer’s brain changes plus brain changes of another type of dementia increases one’s chances of having dementia symptoms in one’s lifetime21,28 compared with someone with Alzheimer’s brain changes alone. It may also account for the wide variety of memory and thinking problems experienced by people living with dementia. Overview 9 Symptoms interfere with most everyday activities Symptoms interfere with many everyday activities Symptoms interfere with some everyday activities Very mild symptoms that may not interfere with everyday activities No symptoms but possible biological changes in the brain Preclinical AD Mild Cognitive Impairment Due to AD Mild Moderate Severe Dementia Due to AD Dementia Due to AD Dementia Due to AD *Although these arrows are of equal size, the components of the AD continuum are not equal in duration. Alzheimer's Disease (AD) Continuum* figure 1 Alzheimer’s Disease Continuum The progression of Alzheimer’s disease from brain changes that are unnoticeable to the person affected to brain changes that cause problems with memory and eventually physical disability is called the Alzheimer’s disease continuum. On this continuum, there are three broad phases: preclinical Alzheimer’s disease, mild cognitive impairment (MCI) due to Alzheimer’s disease and dementia due to Alzheimer’s disease, also called Alzheimer’s dementia (see Figure 1).37-40 The Alzheimer’s dementia phase is further broken down into mild, moderate and severe dementia. While we know the Alzheimer’s disease continuum starts with preclinical Alzheimer’s disease (no symptoms) and ends with severe Alzheimer’s dementia (severe symptoms), how long individuals spend in each part of the continuum varies. The length of each part of the continuum is influenced by age, genetics, biological sex and other factors.41 Preclinical Alzheimer’s Disease In this phase, individuals may have measurable brain changes that indicate the earliest signs of Alzheimer’s disease (biomarkers), but they have not yet developed symptoms such as memory loss. Examples of Alzheimer's biomarkers include abnormal levels of beta-amyloid as shown on positron emission tomography (PET) scans42 and in analysis of cerebrospinal fluid (CSF),43 changes in tau protein in CSF and plasma, and decreased metabolism of glucose as shown on PET scans.44 When the early changes of Alzheimer’s disease occur, the brain compensates for them, enabling individuals to continue to function normally. Although research settings have the tools and expertise to identify some of the early brain changes of Alzheimer’s, additional research is needed to fine-tune the tools’ accuracy before they become available for widespread use in hospitals, doctors’ offices and other clinical settings. It is important to note that not all individuals with evidence of Alzheimer’s-related brain changes go on to develop symptoms of MCI or dementia due to Alzheimer’s.45-46 For example, some individuals have beta-amyloid plaques at death but did not have memory or thinking problems in life.47 MCI Due to Alzheimer’s Disease People with MCI due to Alzheimer’s disease have biomarker evidence of Alzheimer’s brain changes plus new but subtle symptoms such as problems with memory, language and thinking. These cognitive problems may be noticeable to the individual, family members and friends, but not to others, and they may not interfere with individuals’ ability to carry out everyday activities. The subtle problems with memory, language and thinking abilities occur when the brain can no longer compensate for the damage and death of neurons caused by Alzheimer’s disease. 10 Alzheimer’s Association. 2022 Alzheimer’s Disease Facts and Figures. Alzheimers Dement 2022;18. Alzheimer’s Disease Continuum (cont.) When Dementia-Like Symptoms Are Not Dementia It is important to note that some individuals have dementia-like symptoms without the progressive brain changes of Alzheimer’s or other degenerative brain diseases. Causes of dementia-like symptoms include depression, untreated sleep apnea, delirium, side effects of medications, Lyme disease, thyroid problems, certain vitamin deficiencies and excessive alcohol consumption. Unlike Alzheimer’s dementia and other dementias, these conditions often may be reversed with treatment. In addition, the differences between normal age-related cognitive changes (changes in memory, language and thinking) and the cognitive changes of Alzheimer’s disease can be subtle (see Table 2, page 11). People experiencing cognitive changes should seek medical help to determine if the changes are normal for one’s age, are reversible (for example, caused by a new medication or vitamin deficiency), or may be a symptom of Alzheimer’s or another dementia. Among those with MCI, about 15% develop dementia after two years.48 About one-third develop dementia due to Alzheimer’s within five years.49 However, some individuals with MCI revert to normal cognition or do