One of our greatest concerns as we age is our risk for dementia, a severe decline in cognitive function. So many of us ask our health-care providers, “Is dementia hereditary?” especially if a parent suffered cognitive issues.
“Dementia” is an umbrella term for a syndrome constituted by cognitive (and behavioral) symptoms that impair daily life, rather than a disease on its own, explains behavioral neurologist and dementia expert Juan Fortea, MD, PhD. When family members say that a loved one needs help with his/her daily activities, such as getting dressed and making meals, that is describing a syndrome of dementia. A neurologist’s job is to determine what disease is causing that person’s dementia syndrome. Possibilities include Alzheimer’s, the main neurogenerative disease leading to dementia (accounting for 60% to 70% of cases)…Lewy body dementia…vascular dementia…and frontotemporal dementia. Frontotemporal dementia has a strong genetic connection, with up to 30% to 40% of patients having a family history. Lewy body dementia and vascular dementia have lesser genetic connections.
Important: Mild, manageable memory changes are a normal part of aging and don’t typically interfere with daily life. This is distinct from dementia, which involves significant cognitive decline that severely impairs the ability to function independently. Many people can live into their 90s and beyond while maintaining good brain health and cognitive function.
Two types of Alzheimer’s disease (AD)—Down syndrome-associated AD and autosomal dominant AD (ADAD)—are known to be genetically determined.
For people with Down syndrome, amyloid plaques and tau tangles can be seen on imaging tests from age 40, and their lifetime risk for dementia is over 90%. ADAD is a progressive dementia with an onset usually before age 60.
Together, these two types represent only about 1% of all Alzheimer’s cases. The heritability of Alzheimer’s was known to be high (from studies in twins, for example), but until recently, it was thought that less than 1% of Alzheimer’s cases are due to genetics and the other 99% are caused by a mix of genes and environmental factors, from a lack of physical activity to not having a robust social life.
Recent study: One of the strongest genetic risk factors for Alzheimer’s for people of European descent is having the APOE4 gene, which was first associated with Alzheimer’s 30 years ago. New research by Dr. Fortea and his team on APOE4 found that people who carry two copies of the APOE4 gene—meaning they’ve inherited the gene from both parents and so are named “APOE4 homozygotes”—present near full penetrance, meaning that almost all APOE4 homozygotes by ages 60 to 65 show some AD biomarkers. This is not to say that all will develop AD dementia, but previous studies had shown the lifetime risk to be between 40% and 60%.
Dr. Fortea’s research examined clinical, pathological and biomarker changes in APOE4 homozygotes and found that they shared key clinical and biomarker changes with the other genetically determined forms of AD—the predictability of symptom onset and the sequence of biomarker changes mirrored those of people with Down syndrome–associated AD and EOAD, although symptoms started somewhat later in life. APOE4 homozygotes had abnormal amyloid levels in their cerebrospinal fluid and began experiencing AD symptoms around age 65, on average…were diagnosed with mild cognitive impairment around age 72…and with dementia, around age 74. That sequence happens roughly seven to 10 years earlier in APOE4 homozygotes than it does in people without APOE4 who develop AD.
While APOE4 homozygotes account for only about 2% of the overall population, they make up between 15% and 20% of AD cases. This finding raises the number of people whose Alzheimer’s is genetically linked from 1% to as much as 20%.
This study involved only people of European descent, so more work needs to be done to uncover differences in risk among other population groups. Other studies suggest that it is not the same across all ethnicities, highlighting the urgent need for research in other population groups to clarify the potential differences in risk (and the underlying mechanisms).
Separate ongoing research is working to identify the various environmental triggers that could push someone who has genes associated with Alzheimer’s (or other neurodegenerative dementias) toward developing symptoms.
The third Lancet Commission on dementia prevention, intervention and care, led by University College London Professor Gill Livingston, identified two more modifiable risk factors to add to its prior 12 findings. Having high low-density lipoprotein (“bad”) cholesterol from around age 40 and untreated vision loss later in life were added to the list that includes hearing impairment, high blood pressure, smoking, obesity, depression, physical inactivity, diabetes, excessive alcohol consumption, traumatic brain injury and social isolation. The Commission believes that nearly half of all dementia cases could be prevented or delayed by addressing these risk factors.
Indeed, even though there are more cases of dementia now because the population is aging—and the risk for Alzheimer’s and other dementias increases exponentially with age—a 75-year-old woman or man today has lower risk for dementia than a similar woman or man did 50 years ago in most developed countries because we’re addressing those environmental risk factors. People are living healthier lives, and we have better treatments for conditions like hypertension—we know that what’s good for your heart is also good for your brain.
What is not recommended: Widespread genetic testing for APOE4. That’s because we don’t yet have preventive treatments and the potential differential risk across ethnicities.
What you can do now: Consider participating in clinical trials. When there are treatments available—and we might get results from trials in progress now within the next few years—there might be more reason for genetic testing.
The recent FDA approval of Alzheimer’s drugs is a hopeful first step for people already diagnosed with Alzheimer’s. These drugs are proven to modify the disease trajectory even if they aren’t yet as effective as we would like them to be. It’s like driving 100 miles an hour toward a cliff—they can’t stop the car, but they can lower its speed to 70.
