When people think of Alzheimer’s, they usually picture an 80-year-old who starts forgetting names. But the reality is very different — and far more urgent than most people realize.
Some people face a significantly higher risk of developing the disease. Knowing these risk factors is the first step toward acting before it’s too late.
Women: the most affected group
Two thirds of all Alzheimer’s cases worldwide occur in women. For a long time, this was attributed simply to the fact that women live longer. But Dr. Paulo explains that science has now found the real reason: estrogen.
While present in the body, estrogen protects the brain in several ways — it reduces the production of beta-amyloid proteins, accelerates the clearing of plaques, and suppresses neuroinflammation. With menopause, that protection disappears, and the female brain undergoes real structural changes.
Research shows that during menopause, there is a drop in cerebral glucose metabolism and an increase in beta-amyloid deposits. And the earlier menopause arrives, the greater the risk decades later.
There is also a second overlooked factor: women have twice the risk of depression, and untreated depression in middle age increases the risk of Alzheimer’s by up to 70%.
A 65-year-old woman has a one in 5 chance of developing the disease over her lifetime. A man of the same age has a one in 10 chance.
Retirees: when the brain stops being challenged
The Whitehall 2 study, which followed more than 3,400 people for 14 years before and after retirement, showed that verbal memory decline was 38% faster after stopping work.
Dr. Paulo explains why: work keeps the brain in three critical states at once — it forces the prefrontal cortex to make complex decisions, maintains real social connections, and imposes a routine that regulates sleep and stress hormones. When all of this stops at once, the brain loses all three stimuli simultaneously.
Retiring from work does not necessarily mean retiring the brain. Those who keep learning, connecting, and maintaining a sense of purpose protect their minds. Those who stop completely will pay the price years later.
People between 40 and 50 years old
This is one of Dr. Paulo’s most important warnings: Alzheimer’s does not begin with the diagnosis. It begins decades earlier, silently, through habits that seem harmless.
We are seeing a frightening rise in early-onset dementia — people in their 40s and 50s with serious cognitive decline. That name that won’t come to mind, the difficulty staying focused while reading, walking into a room and forgetting why — these are not just signs of tiredness. They may be the first biological warnings that cognitive reserve is running low.
The window to reverse this is not tomorrow. It is now, while there is still autonomy to act.
Carriers of the APOE4 gene
The APOE4 gene is one of the genetic factors most directly linked to Alzheimer’s. Having one or two copies does not guarantee the disease will develop — but it indicates significantly higher risk and calls for extra care with lifestyle habits.
The good news, highlighted by Dr. Paulo, is that even people with a family history and the APOE4 gene showed measurable improvement in cognitive function by adopting lifestyle changes — as demonstrated by the FINGER study, published in JAMA in 2025.
Long-term users of certain medications
This is a warning Dr. Paulo considers essential: prolonged use of certain medication groups is associated with a significant increase in dementia risk.
The four groups that deserve attention are:
- First-generation antihistamines — such as Benadryl and similar allergy medications that cause drowsiness
- Amitriptyline — prescribed for chronic pain, insomnia, and migraines
- Oxybutynin — used for overactive bladder
- Benzodiazepines — such as diazepam and clonazepam, used for anxiety and insomnia
The first three groups block acetylcholine, the neurotransmitter of memory — exactly what is lacking in Alzheimer’s disease. Benzodiazepines work through a different pathway but are also associated with cognitive decline when used long-term.
Dr. Paulo is clear: no one should stop these medications on their own. But it is worth bringing this information to your doctor and asking whether safer alternatives exist for your case.
What these groups have in common
Whether through hormonal decline, cognitive inactivity, genetics, or long-term medication use, all of these risk factors converge on the same point: a brain that does not receive the stimulation and nutrients it needs begins to shrink.
And the Lancet Commission on Dementia is clear: up to 45% of cases could be prevented by eliminating modifiable risk factors. None of them require a prescription. All of them require a decision.
In the next post in this series, we will talk about the silent everyday habits that destroy the brain — and that most people never connect to Alzheimer’s.
The information in this post is based on the work of Dr. Paulo Porto de Melo, neurologist and neurosurgeon, trained at Unifesp and with a postgraduate degree from Harvard, with over 25 years of clinical experience.
Follow Dr. Paulo on Instagram: @ppmelo