What is Alzheimer’s Disease?

Alzheimer’s Disease (AD) is a progressive neurodegenerative disease and the most common cause of dementia. The fundamental causes of AD are still controversial, but β-amyloid (Aβ)-plaques and tau tangles very likely play a role. Distinguishing AD from dementia in general is difficult, since many patients with AD have varying degrees of other dementia, such as vascular dementia, and vice-versa. 

What causes Alzheimer's disease?

Multiple lines of evidence point to β-amyloid (Aβ)-plaques playing an important role in the development of Alzheimer’s Disease (AD): individuals who have mutations that cause an increase in amyloid have early-onset AD and autopsies of individuals with suspected AD show large amounts of amyloid in the brain. However, clinical trials with drugs that decrease the amount of amyloid in the brain have been repeatedly unsuccessful, and so there is substantial debate among the AD research community over the cause(s) of AD.

What are the risk factors for Alzheimer's disease?

• age
• genetics

At what age is Alzheimer's disease usually diagnosed?

Alzheimer's disease becomes more common as people age, with prevalence rising from 5% in people aged 65-74 to over 34% in people aged 85+. This is illustrated in the table below.

How does genetics influence the risk of Alzheimer's disease?

A study using a large genealogy dataset from Utah found that the risk of Alzheimer's diseases (AD) increased with the number of relatives diagnosed with AD in one’s family history, and the younger AD was diagnosed in relatives. The most important genetic contribution to AD risk (outside of rare early-onset AD) is APOE. Everybody has two copies of the APOE gene, which can each have different alleles, from APOE2, APOE3, to APOE4. People with two copies of APOE4 have the highest risk of AD, while people with two copies of APOE2 have the lowest risk.

What are some symptoms of Alzheimer’s disease?

Dementia is a decline in mental function that substantially affects daily life and that exceeds the normal age-related changes (decline in word-finding ability and memory of recent events)  in cognition. When someone displays more unusual symptoms, like getting lost in their own neighborhood or having trouble completing common tasks, this can point to dementia. If a physician suspects dementia, there are validated screening tests they can administer.   

Is there anything I can do to reduce my child’s risk of Alzheimer’s disease?

As explained in the Alzheimer’s disease (AD) whitepaper, genetics plays an important role in determining the risk of AD. Using Orchid’s embryo scoring, you can prioritize the embryo with the lowest genetic risk for AD and reduce their risk of AD. 

Is there anything I can do to reduce my risk of Alzheimer’s disease?

Unfortunately, this uncertainty over the causes of Alzheimer's disease (AD) extends to prevention. There are consistently observed associations between higher levels of education, exercise, and better nutrition and lower rates of AD, but no trials directly examining the impact of intervening on those factors on AD. 

Preventing other dementias

Another type of dementia, which often occurs together with Alzheimer's disease (AD), is vascular dementia. Luckily, a little more is known about the causes of vascular dementia and ways to reduce the risk of it. The American Heart Association and American Stroke Association recommend the following to reduce the risk of vascular dementia:

1. Quitting cigarette smoking
2. Controlling blood pressure

With lower confidence, they also recommended a healthier Mediterranean diet, increased physical activity, and controlling diabetes. A Lancet Commission that focused on dementia overall had similar recommendations but also added:

1. Keeping alcohol consumption low, ideally below 12 units/week
2. Avoiding head injuries
3. Reducing air pollution

Lifestyle changes

Putting that all together, the most practical and impactful steps you can take are:

1. Quitting cigarette smoking
2. Controlling blood pressure
3. Avoiding head injuries
4. Keeping alcohol consumption low
5. Increasing your physical activity

Many of these recommendations reduce the risk of heart disease as well, so they’re probably a good idea even if their impact on Alzheimer's disease specifically is uncertain.

What medications are used to treat Alzheimer’s disease?

Treatment of Alzheimer's disease (AD) is focused on reducing symptoms and consists of acetylcholinesterase inhibitors (there are 3 approved drugs in this category) and memantine. A neurologist would decide when each was appropriate, but acetylcholinesterase inhibitors are generally used in mild/moderate AD, while memantine is added in moderate/severe AD. Since AD can cause other psychiatric symptoms like depression or psychosis, doctors may also prescribe specific medications to treat those symptoms.

How is it diagnosed? 

Diagnosis is tricky

A definitive Alzheimer’s Disease (AD) diagnosis is challenging because dementia can have many causes. The first step is diagnosing dementia, defined as a decline in cognitive function that interferes with work or daily activity and is not explained by delirium or a psychiatric disorder. A neurologist at a memory care clinic is the best person to make a diagnosis of dementia.

Once dementia has been diagnosed, the National Institute of Aging has developed diagnostic guidelines for AD dementia. To simplify, AD dementia is a more likely diagnosis when:

1. Symptoms are very gradual– cognition worsens over months and years.
2. There is no other medical cause for cognitive changes like strokes, other types/causes of dementia, medication use that can worsen cognition, or brain tumors and injury.
3. having specific rare mutations that are known to cause early-onset AD
4. special imaging technology (PET scans) that shows amyloid accumulation in the brain.

The most common type of AD is “amnestic” AD, in which impairment in memory and learning is the first and most obvious symptom. Other types are known as “nonamnestic” and involve worsening of language, execution function, or other skills. 

Can imaging techniques help diagnose Alzheimer’s disease?

There are PET scans that can help with diagnosis of Alzheimer's Disease (AD) by looking for signs of amyloid accumulation in the brain, as well as other imaging techniques like MRI that are less specific for AD. Cerebrospinal fluid, which can be obtained through a lumbar tap procedure, may have elevated rates of amyloid in AD patients, but is still only used for research. In general, most neurologists will make a diagnosis of “probable AD” based only on clinical symptoms, not on imaging. Clinical trials on AD will often use imaging to make sure their patients have AD and not another type of dementia.

Takeaways

1. Alzheimer's Disease (AD) is a progressive neurodegenerative disease that becomes more common with age.
2. There are no lifestyle or medical interventions with solid experimental evidence for preventing or reducing the risk of AD. (But there are observational studies showing that higher levels of education, exercise, and control of cardiovascular risk factors [detailed here] are associated with lower risk of AD.)
3. There are some environmental factors, such as a history of head injury, that probably increase the risk of AD.
4. There are medications that treat the symptoms of AD with mild success.

Where can I learn more?

1. A podcast episode by Dr. Peter Attia, Dr. Richard Isaacson and Lauren Miller Rogen. The episode focuses on genetic and environmental risk factors for AD and some preventative strategies used by Dr. Richard Isaacson, who conducts research on AD and runs a clinic that attempts to prevent AD.
2. A fact sheet from the University of Reading on the APOE gene.