Alzheimer’s disease is the main cause of dementia, accounting for 60% to 80% of all cases. It develops when two abnormal proteins build up in the brain, gradually destroying the connections between nerve cells and eventually killing the cells themselves. But Alzheimer’s is not the only cause. Several other conditions damage the brain in different ways, and in many older adults, more than one type of damage is present at the same time.
How Alzheimer’s Disease Damages the Brain
Alzheimer’s involves two hallmark proteins that accumulate where they shouldn’t. The first, called amyloid-beta, clumps together outside brain cells to form sticky plaques. The second, called tau, twists into tangles inside the cells. Together, these deposits disrupt the signaling between neurons long before visible brain shrinkage occurs. Early memory loss likely stems from soluble forms of these proteins interfering with synapses, the tiny gaps where one neuron communicates with another. As the disease progresses, the plaques and tangles cause structural damage, leading to widespread cell death and the cortical atrophy visible on brain scans.
This process unfolds slowly. Changes in the brain can begin 15 to 20 years before symptoms appear. By the time someone notices persistent forgetfulness or difficulty with familiar tasks, significant damage has already taken place.
Genetics and Alzheimer’s Risk
One gene in particular plays an outsized role. Everyone inherits two copies of a gene called APOE, which comes in several variants. The variant known as APOE4 substantially raises Alzheimer’s risk. People who carry two copies of APOE4 (one from each parent) have roughly a 60% chance of developing Alzheimer’s dementia by age 85. A 2024 NIH study described this two-copy pattern as a distinct genetic form of the disease, not merely a risk factor.
Carrying one copy of APOE4 raises risk to a lesser degree, and carrying zero copies doesn’t eliminate it. Most people who develop Alzheimer’s don’t carry two copies. The gene influences when and whether symptoms appear, but it’s one piece of a much larger puzzle that includes age, cardiovascular health, and lifestyle factors.
Vascular Dementia
The second most recognized cause of dementia involves damage to the brain’s blood supply. Vascular dementia develops when conditions like stroke, small vessel disease, or chronic reduced blood flow deprive brain tissue of oxygen. The damage can be sudden, as when a stroke kills an area of tissue, or gradual, as when tiny blood vessels deep in the brain slowly deteriorate over years. This small vessel damage shows up on MRI scans as white patches and disrupts the brain’s internal wiring, the connections that relay messages between regions.
Risk factors for vascular dementia overlap heavily with those for heart disease: high blood pressure, diabetes, high cholesterol, and smoking. This makes it one of the more preventable forms of dementia, since managing cardiovascular health directly protects the brain’s blood supply.
Lewy Body Dementia
Lewy body dementia is often described as the second most common degenerative cause after Alzheimer’s. It’s driven by clumps of a protein called alpha-synuclein that accumulate inside neurons. These clumps, called Lewy bodies, form in brain regions that control memory, movement, and perception.
What sets this type apart is its distinctive symptom pattern. People with Lewy body dementia commonly experience vivid visual hallucinations, physical symptoms resembling Parkinson’s disease (stiffness, slow movement, tremor), dramatic fluctuations in alertness throughout the day, and a sleep disorder in which they physically act out dreams. These features can appear before or alongside memory problems, which sometimes leads to an initial misdiagnosis of Parkinson’s disease or Alzheimer’s.
Frontotemporal Dementia
Frontotemporal dementia stands out because it typically strikes younger people, often between ages 45 and 65. Rather than memory loss, the earliest symptoms usually involve personality changes, impulsive behavior, or progressive difficulty with language, depending on which part of the frontal or temporal lobes is affected first.
Recent NIH research has linked many frontotemporal cases to dysfunction of a protein called TDP-43, which normally helps regulate how cells read their genetic instructions. When TDP-43 stops working correctly, cells produce abnormal proteins from “cryptic” segments of RNA that healthy cells would normally skip over. This same TDP-43 dysfunction has also been implicated in ALS (Lou Gehrig’s disease) and in a recently identified condition called LATE that mimics Alzheimer’s in older adults.
Mixed Dementia Is More Common Than Most People Realize
Autopsy studies reveal something that clinical diagnoses often miss: many people with dementia have more than one type of brain damage at the same time. Roughly 20% to 22% of dementia cases examined at autopsy show a mix of Alzheimer’s changes and vascular damage. Some studies put the figure even higher, with up to 35% of autopsied brains showing combined lesions. This means the neat categories of “Alzheimer’s” or “vascular dementia” are often simplifications. In reality, the aging brain frequently accumulates multiple types of damage, and these different pathologies compound each other’s effects on thinking and memory.
Conditions That Mimic Dementia
Not everything that looks like dementia is permanent. Several treatable conditions can cause cognitive symptoms severe enough to be mistaken for a degenerative brain disease. The most common reversible causes include depression, medication side effects (particularly drugs with anticholinergic properties), vitamin B12 deficiency, hypothyroidism, and normal pressure hydrocephalus, a condition where fluid builds up in the brain.
These conditions are especially important to investigate in younger people or when cognitive decline happens rapidly. Standard screening typically includes blood tests for thyroid function and B12 levels, a depression assessment, and brain imaging to rule out tumors or fluid buildup. Identifying and treating these causes can partially or fully restore cognitive function, which is why a thorough evaluation matters before anyone assumes a dementia diagnosis is irreversible.
Why Age Remains the Biggest Risk Factor
Regardless of the specific type, advancing age is the single strongest predictor of dementia. The processes behind Alzheimer’s, vascular damage, and Lewy body formation all become more likely as the brain ages. After 65, the risk roughly doubles every five years. This doesn’t mean dementia is an inevitable part of aging. Most people in their 80s do not have dementia. But it does explain why the global burden is growing as populations live longer. The WHO estimates that over 55 million people worldwide currently live with dementia, a number projected to rise sharply in coming decades as the proportion of older adults increases.
Many of the risk factors that feed into these different dementia types are modifiable. Physical inactivity, untreated hearing loss, poorly controlled blood pressure in midlife, excessive alcohol use, social isolation, and air pollution have all been linked to increased risk. None of these guarantees or prevents dementia on its own, but collectively they represent a meaningful window where individual choices and public health measures can shift the odds.