Many of us view dementia and Alzheimer’s as being synonymous with each other, yet the reality is far more nuanced.
According to the charity Race Against Dementia, ‘dementia’ is a general term encompassing symptoms relating to loss of memory, language, problem-solving and other cognitive abilities, with a level of severity that impacts daily life.
While Alzheimer’s is the most well-known of all dementias, and represents the majority of cases, there are at least 200 different types of dementia, each with their own characteristic symptoms and causes.
They range from reversible conditions such as Korsakoff Syndrome – a form of alcohol-related dementia in which heavy drinking affects the person’s ability to absorb vitamin B1, resulting in memory problems – to devastating and little-understood forms such as Creutzfeldt-Jakob disease.
But the more we can characterise the underlying biology behind each type of dementia, the more likely it is that we will be able to pinpoint possible treatment solutions.
“Dementia is a family of different illnesses,” says James Rowe, professor of cognitive neurology at the University of Cambridge. “They’ve all got something in common, but there are also important differences. They will all require different medical approaches and treatment solutions.”
Here are five of the main forms of dementia, what we know about their causes and risk factors, and how scientists are looking to treat them.
1. Alzheimer’s disease
According to Race Against Dementia, Alzheimer’s accounts for around 60-80 per cent of all dementia cases. It is characterised by the steady accumulation of toxic proteins known as tau and amyloid, which form tangles and plaques in the brain. The combination of these toxic proteins and chronic inflammation causes brain pathways to deteriorate gradually over a period of many years or even decades.
In the vast majority of cases, Alzheimer’s is not thought to be hereditary. Instead, risk factors include traumatic brain injuries through repeated blows to the head, age-related hearing loss, cardiovascular problems such as diabetes and high blood pressure, and depression.
The treatment landscape for Alzheimer’s is beginning to look more promising, with the amyloid-clearing drugs lecanemab and donanemab showing small benefits for patients in the early stages of the disease. Other clinical trials are exploring completely new approaches, such as the diabetes drug semaglutide, which aims to reduce brain inflammation by reducing insulin resistance.
Earlier this year neurologists at University College London Hospitals began investigating the first genetic therapy for the disease, which aims to silence a gene linked to the tau protein.
“Tackling dementia is a numbers game,” says Rowe. “It’s beatable and fixable, and the more trials you have, the more chance you’re going to land on a cure.”
2. Lewy body dementia
Around 10 per cent of dementia cases are Lewy body dementia, in which patients develop tiny round deposits of the alpha-synuclein protein known as Lewy bodies, which damage the brain’s nerve cells. Patients also have reduced levels of key brain chemicals, which impacts the connections between cells and causes the brain to function less efficiently.
“Typically, these patients have reasonable memory function, but they cannot plan or organise and their thinking is impaired,” says Philip Scheltens, a scientific advisor at Race Against Dementia and professor of neurology at Alzheimer Center Amsterdam.
Patients with Lewy body dementia can also experience visual hallucinations as well as Parkinson’s-like symptoms such as tremors. Scheltens explains that the advent of better forms of brain imaging in recent years has led to more people being diagnosed with Lewy body dementia, making it easier to design clinical trials.
He points to Boston-based company EIP Pharma, which has developed a drug called neflamapimod, which appeared to significantly improve cognition in patients with the disease in a trial earlier in 2023. “Around those Lewy bodies, there’s a massive amount of inflammation,” says Scheltens. “And this particular drug targets this neuroinflammation.”
3. Frontotemporal dementia
Earlier this year, Hollywood star Bruce Willis revealed his ongoing battle with frontotemporal dementia, a disease that is more likely to affect under-65s. It tends to be characterised by drastic personality change, with individuals often displaying inappropriate and impulsive behaviour.
Dr Maura Malpetti, a senior research fellow at the University of Cambridge and a Race Against Dementia UK research fellow, says frontotemporal dementia is linked to sustained inflammation, which harms the frontal and side regions of the brain. “This inflammation is related to dysfunctional immune activity in the brain,” she says.
Up to 30 per cent of people with the disease are thought to have acquired it due to faulty genes that run in their families. But for more than two-thirds of cases, the exact causes are unknown.
Right now, patients can receive speech and language therapy as well as antidepressants to help manage some of the different symptoms, but there is an urgent need for effective drugs to help slow the progression of the disease.
Malpetti says there are various approaches being studied, which include targeting known faulty genes and cleaning up harmful proteins. Her team is currently researching better ways of dampening down the inflammation that contributes significantly to the disease process.
“We’re using a combination of innovative brain scans and blood tests to identify the most relevant inflammation targets,” she says. “If we find a good inflammation target for frontotemporal dementia, this may have applications in other dementias.”
4. Vascular dementia
This is where brain deterioration is caused by damage to the fragile blood vessels that supply the brain with the oxygen and nutrients it needs to continue functioning. The damage can be caused by small blood clots, which can induce mini-strokes, or the gradual thickening of the blood vessel walls in the brain, which reduces blood flow and leads to cell death.
Symptoms of vascular dementia can include problems with memory, language, decision-making and coordination.
Scheltens says that people with elevated cholesterol, high blood pressure or cardiovascular diseases, such as Type 2 diabetes, are more vulnerable to vascular dementia. “Eighty per cent of the time, blood pressure is the cause of these vascular changes,” he says. “So that and cholesterol changes are really the contributing factors to the vascular changes in the brain that occur relatively late in life.”
The main treatments are a combination of lifestyle recommendations such as increasing exercise, quitting alcohol and smoking, and losing weight, along with medicines to manage blood pressure and cholesterol.
However, cases where dementia is driven entirely by vascular problems are relatively rare. “Most often in elderly patients over the age of 75 or 80, it’s a combination of Alzheimer’s disease and vascular changes on top of it,” he says.
5. Mixed dementia
While mixed dementia has traditionally been regarded as one of the least common forms of the disease, Scheltens says that neurologists are increasingly realising that the vast majority of dementia cases actually feature a mixture of elements from various individual dementias.
“If you ask pathologists, they’ll say that in the elderly, it’s almost all mixed,” he says. “The pure cases of Alzheimer’s are quite rare, and they tend to be people who have early-onset Alzheimer’s. All the rest usually have combinations of Alzheimer’s and vascular changes, or other pathologies such as Lewy bodies.”
He believes that progress in brain imaging will increasingly allow doctors to make more accurate assessments of what exactly is taking place in the brain in each dementia case. In the coming years, this could make it easier to design combinations of therapies and lifestyle interventions that are suitable for each particular patient.
“It’s still early days with some of these disease-modifying treatments which are being developed for Alzheimer’s and other dementias,” he says.
“But in future, the first step will be to inform the patient of lifestyle changes to treat any cardiovascular risk factors, and then try to apply combinations of available treatments.”