Disease Resources

What is Alzheimer’s disease?

Alzheimer’s disease (AD) is a brain disorder that slowly impairs memory and thinking skills. AD is the most common cause of dementia, which leads to a decline in thinking that interferes with one’s everyday functions. An estimated 7 million Americans over the age of 65 have AD, and it is the seventh leading cause of death in the U.S.

What are the causes of Alzheimer’s disease?

In most cases, the cause of AD is unknown. In AD, the brain contains abnormal protein deposits called plaques (made up of amyloid protein) and tangles (composed of tau protein). These deposits begin 10-20 years before a person develops symptoms of the disease. In rare cases, AD is caused by a genetic mutation that leads to excess amyloid protein in the brain. Scientists have learned a great deal about what factors may increase a person’s risk of developing AD. 

The single most important risk factor for developing AD is age. The likelihood of developing AD doubles every 5 years after age 65.

Additional factors that appear to increase the risk of developing AD include:

• Family history of AD
• Other health conditions, such as diabetes and high blood pressure
• Lack of physical activity
• Obesity and/or a poor diet
• Smoking
• Limited education

Learn more about Alzheimer's disease on UofMHealth.org. 

What is frontotemporal dementia?

Frontotemporal dementia (FTD) refers to a group of diseases that damage the frontal and temporal lobes of the brain, resulting in significant changes in behavior, language, and/or motor function.

FTD types can be differentiated by the areas impacted: 

• Behavior
  • Behavioral variant frontotemporal dementia
• Language
  • Primary progressive aphasia (PPA), of which there are 3 types:
    • Semantic PPA
    • Nonfluent/agrammatic PPA
    • Logopenic PPA
• Motor Function (with or without behavior or language problems)
  • Amyotrophic lateral sclerosis (ALS)
  • Corticobasal syndrome (CBS)
  • Progressive supranuclear palsy (PSP)

FTD accounts for only about 5% of all dementia cases in the United States but is one of the most common types of dementia in younger individuals. Approximately 60% of people with FTD are 45 to 64 years old.

What are the causes of frontotemporal dementia?

The cause of FTD is unknown. Those with a family history of the disease are more likely to develop FTD. There are patterns in individuals with FTD, such as loss of neurons and abnormal amounts or forms of proteins called tau and TDP-43. Roughly one-third of FTD cases are inherited. In these individuals, FTD is usually caused by a genetic change that affects (directly or indirectly) one of the above proteins. Genetic testing can reveal an underlying mutation responsible for FTD in about 40% of patients. The diagnosis may be confirmed after death with a brain autopsy.

Learn more about FTD on UofMHealth.org. 

What is Lewy body dementia?

Lewy body dementia (LBD) is a brain disease that impairs thinking and often mobility. It is the third most common cause of dementia after Alzheimer’s disease (AD) and vascular dementia. LBD accounts for up to 20% of all dementia cases in the United States.

What are the causes of Lewy body dementia?

What causes LBD is unknown, but it is not usually hereditary. In LBD, cells in the brain contain abnormal protein deposits known as Lewy bodies that contain a specific protein, alpha synuclein. These affect brain signals and disrupt brain functions. Experts are still exploring factors that are associated with, or alter the risk of, LBD:

• Loss of smell and dream enactment behavior are associated with LBD
• Genetics variants in several genes increase the risk of LBD
• Lifestyle: regular exercise and healthy eating may reduce risk

Learn more about LBD on UofMHealth.org. 

What is LATE type dementia? 

LATE type dementia is a recently characterized type of dementia similar to other types of dementia in that it impairs memory and thinking. However, the causes and the overall rate of progression in LATE make it distinct from other conditions.

LATE is an acronym that stands for:

• Limbic-predominant
• Age-related
• TDP-43
• Encephalopathy

LATE occurs across a set of brain structures known as the limbic regions, considered to be one of the oldest parts of the nervous system. The limbic brain regulates emotions, behaviors, motivations, and certain aspects of memory. 

LATE typically affects people over the age of 80, and involves the abnormal buildup of a protein called TDP-43 within the limbic regions, rather than the typical amyloid plaques and tau tangles that are found in Alzheimer’s disease.

What are the causes of LATE? 

TDP-43 is an essential protein required for brain cells (neurons) to function. In LATE, the buildup of TDP-43 interferes with its normal activity, directly affecting the function of neurons in the limbic regions of the brain. This, in turn, results in the gradual loss of memory—in particular the ability to form new memories—characteristic of LATE. 

Because LATE was only recently recognized, we do not yet truly understand just how common this condition is. Nevertheless, in large studies of people over the age of 80, ~40% were found to have TDP-43 deposits, and 25% of those had experienced problems with their memory. As described below, because LATE can only be diagnosed on autopsy, it may be that LATE is much more common than we know.

Learn more about LATE on UofMHealth.org. 

What is mild cognitive impairment?

Mild cognitive impairment (MCI) is a decline in thinking abilities that is greater than expected based on a person’s age. However, the decline does not impair the person’s ability to complete daily activities (as compared to dementia, in which the decline interferes with daily activities). It is important to recognize MCI because it puts a person at a greater risk of developing dementia in the future.

What are the causes of mild cognitive impairment?

MCI has many potential causes, not all of which are completely understood. Experts believe that many cases – but not all – result from brain changes occurring in the early stages of Alzheimer’s disease or a similar disease.

Learn more about MCI on UofMHealth.org. 

What is Posterior Cortical Atrophy?

Posterior cortical atrophy (PCA) is a brain condition in which the back part of the brain (the posterior cortex) slowly deteriorates. This area helps us see and understand the world by recognizing objects, reading, judging distance, and navigating. Unlike Alzheimer’s disease (AD), memory may be maintained at first, and problems with vision-related tasks are the early signs.

What are the causes of Posterior Cortical Atrophy?

PCA is a clinical syndrome. This means it describes a pattern of symptoms and brain changes rather than a single disease. In most people, PCA is caused by Alzheimer’s disease. Many studies show that the majority of people with PCA have positive amyloid and tau biomarkers, consistent with AD. A smaller group have other causes such as Lewy body dementia, corticobasal degeneration, or (rarely) prion disease.

What is the prevalence of Posterior Cortical Atrophy?

PCA is underrecognized and definitions have varied but specialists report that roughly 5% of people with AD present with a PCA-type profile. In early-onset AD (symptoms before age 65), this can be around 8–13%. PCA most often begins between ages 50 and 65, though it can occur earlier or later.

What are the symptoms of Posterior Cortical Atrophy?

Symptoms vary across people and change over time. Early features reflect problems in the visual processing networks:

• Difficulty reading (losing place on the page, letters seem to move or blur)
• Trouble judging distance or depth; bumping into objects; getting lost in familiar places
• Problems recognizing objects or seeing more than one object at a time (simultanagnosia)
• Difficulty with spatial tasks like dressing (finding sleeves) or using tools/appliances
• Problems with calculations, spelling, or writing
• Hallucinations can occur in some people, especially if Lewy body disease is present
• Memory and insight are often relatively preserved early on, but decline later

How is Posterior Cortical Atrophy diagnosed?

PCA may be missed at first because eye exams are often normal. In 2017, international experts agreed on research consensus criteria for diagnosing the PCA syndrome and describing the likely underlying disease (for example, PCA due to Alzheimer’s disease). Evaluation usually includes a neurological exam, neuropsychological testing focused on visuospatial skills, and brain imaging.

Helpful tests include:

• MRI (often shows thinning/atrophy in occipital and parietal lobes)
• FDG-PET (often shows reduced metabolism in posterior brain regions)
• Tau PET and amyloid PET, or CSF/plasma biomarkers (often positive for Alzheimer’s disease in PCA)

What are the prognosis and treatment options?

PCA is progressive. Over the years, visuospatial problems usually worsen and other thinking
skills can decline, but this varies across people. There is no cure specific to PCA yet. Management focuses on symptoms, safety, and quality of life. If biomarkers show Alzheimer’s disease (the most common cause), standard AD medications are often used:

• Acetylcholinesterase inhibitors (for mild to moderate stages)
• Memantine (typically for moderate to severe stages)

Evidence in PCA specifically is limited, so decisions are individualized. Because many people are younger at onset, early support for work, driving, and family responsibilities is important.

Non-drug supports also matter a lot:

• Occupational therapy and environmental changes (good lighting, high contrast labels, decluttering, clear pathways)
• Reading aids and strategies (e.g., line guides, larger fonts, text-to-speech tools)
• Mobility strategies (reduce shadows and visual complexity; consistent lighting)
• Education and counseling for patients and families; driving safety and planning ahead

What is primary progressive aphasia (PPA), and what are the signs and symptoms?

PPA is a type of dementia in which language abilities are the primary symptoms. Initial cognitive symptoms include difficulty with word-finding, repetition, naming, language comprehension, and articulation. Swallowing difficulties may also be present.

How is PPA caused, and what are the risk factors? 

PPA can be caused by deposits of proteins such as tau, amyloid or TDP-43 in the brain. Damage in specific areas within the frontal, temporal, and parietal regions of the brain, along with specific language symptoms, dictates the particular type of PPA an individual may have. Some cases of PPA are inherited and have been tied to mutations in the genes GRN and MAPT.

PPA may cause changes in behavior.

Individuals with PPA are often aware of their communication difficulties, which may cause frustration, depression, anxiety, apathy or social withdrawal. Later in the disease course, behavioral problems such as impulsivity and disinhibition may occur. Movement problems like clumsiness or balance problems may also be present.

Where can I learn more?

• Association for Frontotemporal Degeneration: Primary Progressive Aphasia

What is vascular dementia?

Vascular dementia refers to changes to memory, thinking, and behavior that occurs when blood flow to the brain is reduced, and brain cells are deprived of oxygen and nutrients. Vascular dementia is considered the second most common cause of dementia after Alzheimer’s disease, accounting for up to 30% of cases.

What are the causes of vascular dementia?

Any condition that damages the brain’s blood vessels can lead to vascular dementia. These “vascular risk factors” include:

• Age
• High blood pressure
• High cholesterol
• Diabetes or high blood sugar
• Smoking
• Little or no physical exercise
• Unhealthy diet
• Obesity
• Obstructive sleep apnea
• Hardening of arteries anywhere in the body

Learn more about vascular dementia on UofMHealth.org.