Is dementia caused by genetics? | Prof. Claire Steves

Summary

The transcript discusses genetic and environmental factors contributing to dementia, emphasizing early onset in people aged 50-60. The APOE4 gene increases dementia risk, though lifestyle factors can still build cognitive resilience. Brain development is influenced by maternal nutrition, education, and psychological factors starting from fetal life. Physical activity and social engagement are key in boosting brain reserve, while inflammation and other health issues can accelerate cognitive decline. Exciting new drugs slow disease progression but carry risks, such as brain swelling, limiting their widespread use.

Takeaways

• 🧬 Genetic factors play a significant role in early-onset dementia, with genes like APOE4 increasing the risk.
• 🧬 Having two APOE4 alleles increases the risk of dementia eightfold, but it's not a guarantee.
• 👶 Early life experiences, including in utero, significantly affect cognitive reserve and future dementia risk.
• 🍽 Nutrition and stimulation from an early age are crucial for brain development and resilience against dementia.
• 🏃‍♂️ Physical fitness and social activity contribute to a healthy brain reserve, which can delay the onset of dementia symptoms.
• 🧠 High cognitive functioning gives individuals a greater reserve, allowing dementia symptoms to appear later in life.
• 🚭 Lifestyle factors like smoking and alcohol consumption can negatively impact brain development and increase dementia risk.
• 👨‍⚕️ New antibody-based medications can remove proteins associated with Alzheimer's disease, slowing its progression.
• 💊 While these new drugs show promise, they only modestly improve cognition and come with risks like brain swelling.
• 🏥 Regular brain scans are required for patients on these new medications, highlighting logistical and resource challenges.

Q & A

What is the role of genetic factors in the development of dementia?

Genetic factors are important in the development of dementia, especially in early-onset dementias, which typically occur in people in their 50s or 60s. Specific genes, such as the APOE gene, play a significant role in increasing the risk of dementia.

What is the APOE gene, and how does it influence the risk of dementia?

The APOE gene comes in different forms, including APOE4, which is associated with an increased risk of dementia. People who carry two copies of the APOE4 gene have about an eight times greater risk of developing dementia, though it is not guaranteed they will get the disease.

What percentage of the population has two copies of the APOE4 gene?

About 2-3% of the population has two copies of the APOE4 gene, while around 25% of people have one copy of the gene.

Can environmental factors also influence the risk of dementia?

Yes, there is an interaction between genes and the environment that can be important in influencing dementia risk. Environmental factors such as diet, medications, and lifestyle choices can affect the brain's resilience, even in people with genetic predispositions.

How does early-life development, including fetal conditions, affect the risk of dementia later in life?

Factors affecting brain development in utero, such as maternal nutrition and environmental exposure, can influence cognitive reserve and the risk of dementia later in life. Higher cognitive reserve helps delay the onset of dementia symptoms.

What is cognitive reserve, and why is it important in dementia?

Cognitive reserve refers to the brain's ability to cope with damage and maintain function. Individuals with higher cognitive reserve can better withstand brain damage caused by dementia and delay the onset of symptoms that interfere with daily life.

What are the lifestyle factors that contribute to building cognitive reserve in children?

Key factors include intellectual stimulation, social engagement, psychological stability, and good nutrition. Physical activity and reducing sedentary behavior are also important in building cognitive and brain reserve.

How does physical fitness benefit brain health?

Physical fitness is beneficial for both vascular and brain health. Regular physical activity, even outside of structured exercise, improves brain function, reduces sedentary time, and helps slow brain aging.

What are some early signs of dementia that people should watch for?

Early signs of dementia include changes in cognitive function, such as short-term memory loss (in Alzheimer's disease) or personality changes. Some forms of dementia may also manifest through physical symptoms like balance problems, blood pressure regulation issues, or sleep disturbances.

What is the current status of treatment options for dementia?

There are new antibody-based medications that target the proteins associated with Alzheimer's disease, removing them from the brain and slowing the progression of the disease. However, these drugs provide modest improvements and come with risks, such as brain swelling and microhemorrhages, which require regular monitoring through brain scans.

Outlines

00:00

🧬 Genetic Factors in Early-Onset Dementia and APOE4 Risk

This paragraph discusses the role of genetic factors in the development of dementia, particularly in early-onset cases (50s-60s). The APOE4 gene is highlighted as a significant risk factor, with those possessing two copies having an eight times higher risk of developing dementia. However, it's emphasized that having the APOE4 gene does not guarantee the disease. The gene's influence is linked to how brain cells use fats, which can be affected by diet and medications, making lifestyle factors crucial in managing dementia risk.

05:01

👶 Cognitive Reserve: Early Life Factors Influencing Dementia

This paragraph explores how early life, even in utero, affects cognitive reserve, which in turn impacts dementia risk later in life. Cognitive reserve refers to an individual’s maximum cognitive ability, encompassing intellectual and psychological health. Higher cognitive reserve helps delay the onset of dementia symptoms. The discussion extends to how stimulation, education, parental influence, and nutrition in childhood shape cognitive development. Smoking, alcohol, and environmental factors are also mentioned as key influences on brain development.

10:02

🧠 Mental Health's Impact on Brain Reserve and Dementia

The link between mental health and brain reserve is explained here. Good mental health fosters opportunities and motivation for activities that improve brain reserve, while poor mental health can hinder cognitive resilience. Social stimulation, physical activity, and overall fitness are highlighted as key factors in enhancing brain and vascular health. The reduction of sedentary behavior and maintaining physical activity, even without formal exercise, are noted as beneficial for brain aging. Interactions between other body systems, such as cardiovascular health and sensory functions, also influence cognitive decline.

💊 New Dementia Drugs: Progress and Risks

This paragraph delves into the recent advancements in dementia treatments, particularly new antibody-based drugs that target and remove brain proteins associated with Alzheimer’s disease. While this represents a breakthrough in slowing down disease progression, the benefits are modest, with only a slight cognitive improvement over a year. The risks, however, are significant, including brain swelling and micro-hemorrhages, which necessitate regular brain scans. These side effects create uncertainty regarding the overall benefit-risk balance, limiting the widespread use of these treatments, especially outside of the U.S.

Keywords

💡Genetic Factors

Genetic factors refer to the role that inherited genes play in the development of diseases, in this case, dementia. The video highlights that genetic factors are particularly important in early-onset dementias, which affect people in their 50s or 60s. The interaction between these genes and environmental factors is emphasized as a significant contributor to the disease.

💡APOE4

APOE4 is a variant of the apolipoprotein E gene that is associated with an increased risk of developing dementia, specifically Alzheimer's disease. People who inherit two copies of the APOE4 gene have up to eight times the risk of developing dementia compared to those without it. Despite this, having the gene does not guarantee the onset of dementia, as other factors such as diet and medication can influence brain health.

💡Cognitive Reserve

Cognitive reserve refers to the brain's ability to compensate for damage and maintain function despite the onset of dementia. The video explains that individuals with higher cognitive reserves, achieved through factors like education, intellectual stimulation, and psychological well-being, can delay the point at which cognitive decline interferes with daily life. This is why early-life experiences, including nutrition and mental health, are critical for brain health later in life.

💡Nutrition

Nutrition is discussed as a vital factor that affects brain development starting in utero. A mother's diet during pregnancy and the child's nutrition in early life play a role in the development of the brain and future cognitive reserves. The video emphasizes the long-term impact of nutrition on the likelihood of developing dementia later in life.

💡Physical Activity

Physical activity is highlighted as a key factor in maintaining brain health and delaying cognitive decline. Regular physical exercise, or even just reducing sedentary time, is linked to improved vascular health and brain aging. This lifestyle habit contributes to physical reserve and helps slow down processes that could lead to dementia.

💡Mental Health

Mental health is described as an important determinant of brain health and cognitive reserve. Good mental health in early life can lead to a cascade of positive outcomes that strengthen cognitive reserve, while poor mental health can limit a person’s ability to engage in activities that support brain health. The video discusses how mental health influences motivation, opportunities, and the ability to maintain cognitive function into later life.

💡Social Stimulation

Social stimulation involves engaging in social activities that challenge and stimulate the brain, which can help build cognitive reserves. The video suggests that social interactions and mental engagement are important contributors to maintaining brain function and delaying cognitive decline. People who are more socially active tend to have better cognitive outcomes in later life.

💡Early Symptoms of Dementia

The early symptoms of dementia vary depending on the type of dementia, but common signs include short-term memory loss, personality changes, and difficulty with tasks like blood pressure regulation or movement. The video advises that noticing a change in cognitive function, such as difficulty remembering things or personality shifts, should prompt individuals to seek medical advice.

💡New Treatments for Dementia

New treatments for dementia are antibody-based medications that aim to remove protein build-ups in the brain, such as amyloid plaques, which are associated with Alzheimer's disease. While these drugs have shown proof of concept, their effects on slowing cognitive decline are still modest. They come with risks, such as brain edema and hemorrhage, and require monthly brain scans, making them a controversial and resource-intensive treatment option.

💡Environmental Factors

Environmental factors, such as diet, education, social stimulation, and mental health, play a crucial role in the development and progression of dementia. The video emphasizes that, even with genetic predispositions, these external factors can influence whether or when dementia develops. The interaction between genetics and the environment is key to understanding why some people develop dementia while others do not.

Highlights

Genetic factors are crucial in the development of dementia, especially in early onset cases.

The APOE gene, particularly the APOE4 variant, is linked to an increased risk of dementia.

Having two APOE4 alleles multiplies the risk of dementia by eight times.

Only a small percentage of the population has two APOE4 alleles.

The APOE4 gene's influence on dementia risk is related to how brain cells use fats.

Diet and medication might affect how APOE4 impacts dementia risk.

Cognitive reserve, influenced by early life experiences, can delay the onset of dementia symptoms.

Factors such as nutrition and stimulation during early life contribute to cognitive reserve.

Mental health in early life can set up a cascade of benefits for later brain health.

Physical fitness and social activity are key to building brain reserve.

Cardiovascular health is closely linked to brain health.

Infections and chronic inflammation can affect brain resilience.

Symptoms of dementia can vary and may include memory loss, personality changes, and even falls.

Most people referred to memory clinics are in their 70s, with early onset cases being rare.

New antibody-based drugs can clear proteins associated with Alzheimer's disease.

These new drugs slow the progression of dementia, rather than cure it.

The new drugs come with risks, such as brain swelling and micro hemorrhages.

The balance of risks and benefits of the new drugs is still unclear.

The new drugs are not yet approved in the UK due to logistical and safety concerns.

Transcripts

we know that genetic factors are

important in the development of dementia

and they're most important in the early

onset dementias so people who have

developed Dementia in their 50s or 60s

there's an interaction between those

genes and the environment which might be

very important so one of the most you

know talked about because it's actually

really important Gene is apoe of which

all of us have two um there's an apoe4

is associated with increased risk of

dementia

um and so if you have two of those

you're actually much greater risk of

having dementia it doesn't mean it's

definite if you have these two what do

you call them E4

gen it's about eight times greater risk

okay so that sounds pretty bad how and

how many people will have two of these

not very many so I think it's um you say

about 25% of the population have one so

there'll be a couple of percent of

people like two or three% people

listening to this who could have both

and their risk really would be much much

because eight times higher on something

that's Rel ly common sounds like that's

a very high risk yeah so that and that's

one of the reason you're saying they're

not doomed to get this if they have

these two absolutely not yeah well we

don't actually know completely why apoe4

confers the risk but it's something to

do with the way that our brain cells um

use um fats in the body and it's

probably influenced by things in our

diet and maybe medications that we take

so that's why you know you can still

increase your resilience even if you

have two of those Appo E4 Al what are

the other things that um mean that

people are at higher risk of dementia

well if we start like early on in life

um really important because ultimately

all of ourselves in our body are aging

right from the beginning when we're

after we've conceived um so you know

even things in utero can be really

important for later life development

this is while I'm a while I'm a fetus so

so if you any pregnant Ms out there you

know actually you know what you're doing

is preparing your child for the whole of

their life I mean that's really a key

message for society we need to really

look after pregnant moms that seems

unobvious how does what happens to me as

a fetus affect what are the things that

will change my risk of demure it's about

cognitive Reserve so that's the kind of

Maximum cognitive ability that we might

have not just in terms of sort of

intellectual ability but also

psychological um State as well so the

reason why that's important for dementia

is is that dementia is something whereby

our functions are interfering with daily

life and obviously if we start off with

really high functioning then we get to

that point much later in any disease

process so you can put off significantly

the time at which you fall below that

threshold of being able to function in

daily

life much much later could you explain a

bit more what you're describing what is

it that some people are getting and

other um other people are not we can

think about it from multiple different

ways yeah we can think about it in terms

of the stimulation that a child is being

given um through education through

parental influence we can think about it

psychologically around that that

development um that's happening in early

childhood but we can also think about it

about nutrition as we talked about you

know before I'm sure we'll talk about

again uh nutrition starts and neutro

there are factors factors which effect

how the brain actually develops right

from the beginning and then you know we

can then go even further than that and

talk about things like smoking and

alcohol which have significant effects

on the brain development of children I

think I'm understanding um better now I

think you're saying right back even when

you're as a fetus depending upon like

the nutrition that your mother is having

that's going to affect the way your

brain is developed then after you're

born continuing the food that you eat as

a child but also you're saying the

stimulation you get I'd love for you to

talk a little bit more about that you're

saying that somehow the way that the

world is interacting with you is going

to give me a I guess like a healthier or

more robust brain that is actually going

to have an effect on whether I get

dementia 70 or 80 years later is that

you might still get dementia but humors

are incredibly varied in terms of their

uh you know cognitive

functioning um and so if you have a high

cognitive functioning obviously um

you've got further to fall could you

talk a little bit more therefore about

this because I think everyone listening

to this is probably thinking okay how do

I make sure that um maybe starting with

perhaps thinking about their children or

their grandchildren how do they make

sure their reserves are good and then

also um you know perhaps what's

happening later but right now I think

you're talking about like earlier life

what is it that gives you these higher

reserves be you know before you're 18 I

guess yeah so so I think we we've we've

already talked about diet we've talked

about intellectual stimulation sort of

also that stability psychological

balance mental health is really

interesting because it and ends up good

mental health sets you up for a Cascade

of of of good things then happening to

you late in life which then give you

more opportunity more capability to take

on these opportunities to then um

improve your brain reserve and stimulate

your brain whereas um problem

problematical me mental health then can

lead to difficulties in CA the

capability or the opportunities the

motivations to take on these things that

are going to then help your um future

brain Reserve so so talking about some

of those I mean the key things are

around social stimulation um uh you know

um things like physical fitness I think

I talked about that a lot in the last

podcast that we know that that physical

fitness is really beneficial for brain

health and of course we can then put in

some physical Reserve as well and habits

of daily life that then increase our

physical activity and Contin it going

through midlife which is going to be

good for vascular Health but it's also

really good for brain health so if I am

doing more physical

activity what does that mean for my

brain The Habit is good it's the it's

the daily regular um physical activity

which doesn't need to entail exercise um

it's the um reduction even in sedentary

time that we see has an effect not just

on dementias but actually on brain aging

as well but not just in terms of

physical activity active in terms of

social activity and all those things

those all contribute to brain Reserve

but then there's also things that sort

of you know alter brain reserve and make

it more tricky for us to maintain those

cognitive functions I'm not talking

about the protein opes now I'm talking

about the the reserve capacity and of

course there that's where interaction

with other body systems is really

important so we know that there's a real

strong interaction between cardiol

health and brain health we know that

there's a really strong interaction

between um say for example um uh our

hearing our hearing ability our sensory

ability and brain health then likewise

infections can can tip the balance of

brain health but chronic inflammation

can also affect how our brains resilient

um to those changes which might happen

in that balance between proteins being

set down or not so before we start to

talk about prevention which I I know

everyone listening is like that's really

interesting yeah all sounds quite scary

let's talk about everything we can do um

I'd love to talk a little bit about

symptoms and what the status of

treatment is at the moment for us

so could you tell me if someone's

thinking about the symptoms that they

might notice in themselves or a loved

one that would sort of probably trigger

this thing that I think you know we

should maybe go and talk to a doctor

what should they be looking for so

really it's about a change in in

cognitive function

and different dementias have different

patterns but as I've talked about you

know we we've got things like

Alzheimer's dementia which starts with

short-term memory loss um there's other

um forms of dementia that can start with

um personality change um again further

forms of dementia actually the first

presentation is around falling over and

maybe um uh difficulty with the blood

pressure regulation um sleep even

sometimes can be the very earliest

presentations of some forms of dementia

when those symptoms start to become

become common enough that you might be

sort of on the alert for it because

again I I think many people listening

feeling like ah as people get old I'm

I'm expecting this to happen and I'm

sort of on become very Vigilant about

it good question so most people that are

referred to my memory Clinic are

probably in their 70s okay it's quite

rare to see people in their 40s being um

being referred to me um if people do

have these these problems happening in

their 40s then they're more likely to go

and see a

neurologist U for an examination and so

what are the treatment options and I

think um I've definitely seen there's

been a lot of press about new drugs

starting to come on board um what's the

what's the situation today as as a

doctor thinking about treatment for

somebody who comes in and who you do

diagnose with dementia yeah so it's

really exciting that we now have some

new drugs because we've been waiting

actually about 20 years for some new

changes in drugs and what what these

drugs are doing actually it's a really

amazing proof of concept that um these

medications they're basically antibody

based medications that are sticking to

the proteins and getting rid of them

clearing those proteins that we talked

about at the beginning um and know yeah

yeah we've known for some time actually

that we can do this and take them out

for example from um from animal studies

um it's only really been in the last

year that we've had evidence that um

taking out those proteins in the case of

Alzheimer's uh disease actually has an

effect on human progression of the

disease but the issue is that actually

when we do that the level of gain is

actually quite modest it doesn't you

mean when someone takes these drugs yeah

so we can take the take the the proteins

out of the brain right but it doesn't

necessarily mean that we've

significantly affected their cognition

and their function we hear about all

sorts of one under drugs right that

suddenly solve everything um and then

you hear about other drugs where people

say oh well it doesn't really you know

ultimately didn't really make much of a

difference how excited are you well I'm

excited in principle I'm excited in

principle because we've shown a proof of

principle that this works in humans and

therefore it could be developed on um

but the issues are this that first of

all the gain over a year is only a few

points on a cognitive measure so it

doesn't get it doesn't mean that the

person then doesn't have dementia it's

just that their Dem they're not they're

not cured they probably are the you know

the process is slowed though that's the

new that's the the GameChanger the

process is slowed whereas before we've

been able to give drugs that manage

symptoms but ultimately the process

isn't slowed so that's the really

exciting Game Change how much slowing

down are they delivering so at the

moment not very much slowing down okay

so that's but but we haven't we haven't

talked about the main problem with it

the main problem is is that actually

increase risk so as you're taking away

the proteins from the brain okay you're

also increasing the risk of Edema

happening in the brain so that's

swelling swelling in the brain okay

which can be quite catastrophic if the

brain swells a little bit there inside a

a fixed space there's an increased risk

of hemorrhage little micro hemorrhages

within the brain and so people that are

having these there bleeding yeah so the

people that are having these medications

have to have a scan every month and so

what does that mean in reality there

because those sound like quite scary

side effects are they

it means that um actually the balance of

risks and benefits is not totally clear

ultimately so as a doctor does that mean

you're not necessarily just saying to

everybody who comes in you should take

this TR well they're not they're not

approved in the UK for that reason and

they have been approved in the states

they've been approved in the states yeah

okay nor when that happens that tells

you it's a bit on the edge is that what

you're saying about the balance of

benefit and I think benefit and risk is

definitely on the edge if you had all

the resources available and then you've

got to think well actually how are we

logistically going to get everybody to

be able to have scans every month and

what KnockOn effect is that going to be

on being able to get can scans for

cancer or scans for other things so

there's a resource issue as well