About 60% of people with FTLD are ages 45 to 60.13 Scientists think that FTLD is the most common cause of dementia in people younger than 60.13 In a systematic review, FTLD accounted for about 3% of dementia cases in studies that included people 65 and older and about 10% of dementia cases in studies restricted to those younger than 65.14 Cause Characteristics TABLE 1 7 Common Causes of Dementia and Associated Characteristics Parkinson’s disease (PD) Problems with movement (slowness, rigidity, tremor and changes in gait) are common symptoms of PD. Cognitive symptoms develop either just before movement symptoms or later in the disease. In PD, clumps of the protein alpha-synuclein appear in an area deep in the brain called the substantia nigra. These clumps are thought to cause degeneration of the nerve cells that produce dopamine.15 As PD progresses, alpha-synuclein can also accumulate in the cortex of the brain (similar to dementia with Lewy bodies). Dementia may result. Hippocampal sclerosis (HS) HS is the hardening of tissue in the hippocampus of the brain. The hippocampus plays a key role in forming memories. The most pronounced symptom of HS is memory loss, and individuals may be misdiagnosed as having Alzheimer's disease. HS brain changes are often accompanied by accumulations of a misfolded form of a protein called TDP-43. HS is a common cause of dementia in the "oldest-old," individuals age 85 or older. Mixed pathologies When an individual shows the brain changes of more than one cause of dementia, mixed pathologies are considered the cause. When these pathologies result in dementia symptoms during life, the person is said to have mixed dementia. Studies suggest that mixed dementia is more common than previously recognized, with more than 50% of people with dementia who were studied at Alzheimer's Disease Research Centers having pathologic evidence of more than one cause of dementia.12 In community-based studies, the percentage of mixed dementia cases is considerably higher.11 The likelihood of having mixed dementia increases with age and is highest in people age 85 or older.16-17 Overview these genetic mutations usually develop symptoms at the same or nearly the same age as their parent with Alzheimer’s). Glucose metabolism began to decrease 18 years before expected symptom onset, and brain atrophy began 13 years before expected symptom onset. Another study1 of people with DIAD found abnormal levels of the neurofilament light chain protein, a biomarker of neurodegeneration, 22 years before symptoms were expected to develop. A third study2 found that levels of two types of tau protein begin to increase when beta-amyloid starts clumping together as amyloid plaques. Levels of these types of tau increase as early as two decades before the characteristic tau tangles of Alzheimer’s begin to appear. Mixed Dementia Many people with dementia have brain changes associated with more than one cause of dementia.11,18-23 This is called mixed dementia. Some studies11-12 report that the majority of people with the brain changes of Alzheimer’s also have the brain changes of a second cause of dementia on autopsy. One autopsy study showed that of 447 older people who were believed to have Alzheimer’s dementia when they died, only 3% had the brain changes of Alzheimer’s disease alone, 15% had the brain changes of a different cause of dementia, and 82% had the brain changes of Alzheimer’s plus at least one other cause of dementia.11 Studies suggest that mixed dementia is the norm, and the number of distinct combinations of mixed dementia is extensive.24-25 Mixed dementia is especially common at advanced ages.18,26 For example, the oldest-old, those age 85 or older, are more likely to have evidence of two or more causes of dementia than those younger than 85.16-17 Having Alzheimer’s brain changes plus another type of brain change makes it more likely that a person will show dementia symptoms in their lifetime11,18 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. Cause Characteristics TABLE 1 (cont.) 8 While we know the continuum starts with preclinical Alzheimer’s and ends with severe Alzheimer’s dementia, how long individuals spend in each part of the continuum varies. The length of each phase of the continuum is influenced by age, genetics, biological sex and other factors.