Alzheimer’s disease is the most frequent cause of dementia and one of the great health challenges of ageing. Its onset is usually slow and insidious, first affecting the areas of the brain related to memory, thinking and language, especially structures such as the hippocampus and the entorhinal cortex, which are essential for consolidating memories.
In the early stages, symptoms can be confused with the ordinary forgetfulness of age. However, the disease advances progressively and ends up affecting other cognitive functions and personal independence. Over time, people with Alzheimer’s may stop recognising their closest relatives and experience major difficulties in basic activities of daily living, such as dressing, washing, orienting themselves or preparing food.
In addition to memory problems, other frequent symptoms are impaired reasoning, aphasia (language difficulties), apraxia (problems carrying out learned movements), loss of spatial ability and changes in personality or character, such as apathy, irritability, agitation, suspiciousness or disinhibition.
The scale of the problem
The impact of Alzheimer’s is growing because of the ageing of the population. At present, more than 55 million people are living with dementia worldwide, and it is estimated that this figure could reach 78 million by 2030 and 150 million by 2050.
In Europe, 2025 data estimate more than 9 million people with dementia in the European Union and more than 12 million across the continent as a whole. In Spain the situation is particularly significant: it is calculated that close to one million people are living with dementia, and Alzheimer’s accounts for approximately 70% to 77% of cases. Spain could also be one of the European countries with the greatest growth in cases in the coming decades.
A greater impact on women has also been observed. In fact, around 65% of people with dementia are women, which reinforces the need to study this disease from a gender perspective as well.
Pathological features
The pathological features of Alzheimer’s disease include a progressive formation of senile plaques and neurofibrillary tangles in the cerebral cortex, as well as neuronal and synaptic loss.
Senile plaques are mainly formed by deposits of beta-amyloid, a protein that accumulates outside the neurons. Neurofibrillary tangles, for their part, are produced by an alteration of the tau protein, which under normal conditions helps maintain the internal structure of the neuron. When this protein becomes hyperphosphorylated, it loses its function and clumps together inside the nerve cells, contributing to their deterioration and death.
This whole process causes a progressive disconnection between neurons, a reduction in synaptic communication and, ultimately, brain atrophy visible on neuroimaging.
Genetic and risk factors
Although most cases are sporadic, there is an important genetic component. In a small percentage of cases, especially those of early onset, the disease is related to mutations in three specific genes:
- APP
- PSEN1
- PSEN2
These hereditary forms usually appear before the age of 65.
In late-onset cases, the best-known genetic susceptibility factor is the APOE ε4 allele, which increases the risk of developing the disease and may influence a faster progression.
Alongside genetics, modifiable risk factors have also been identified that can contribute to the onset or progression of Alzheimer’s, such as:
- Diabetes mellitus
- Cardiovascular disease
- Sedentary lifestyle
- Malnutrition
- Traumatic brain injury
- Untreated hearing loss
- Vision loss
- Social isolation
This reinforces the idea that brain health is closely related to vascular, metabolic and functional health.
Clinical course
Alzheimer’s disease does not appear abruptly, but rather develops in several stages.
Preclinical phase
Brain changes can begin years before the first visible symptoms appear. At this stage there is still no clear functional impairment, although beta-amyloid deposits and tau alterations are already occurring.
Mild cognitive impairment
At this stage the first memory failures appear, especially for recent events, together with subtle difficulties in language, organisation or orientation. The person still retains much of their independence, but begins to notice that some tasks require more effort.
Mild to moderate dementia
Here the deterioration clearly interferes with daily life. Problems arise with managing money, following conversations, planning activities, recognising places or keeping to a routine. Agitation, apathy, sleep disturbances or episodes of wandering may also appear.
Severe dementia
In the advanced stage, dependence is almost total. The person loses much of their language, stops recognising their surroundings, and presents incontinence, difficulty swallowing and significant physical deterioration. At this stage, care is continuous.
Diagnostic criteria
For a diagnosis of Alzheimer’s disease, the following diagnostic criteria must be met together:
- Dementia established by clinical diagnosis and documented by testing.
- Deficit in two or more cognitive areas.
- Progressive worsening of memory and other cognitive areas.
- No alteration of consciousness.
- Onset between the ages of 40 and 90.
- Absence of another brain or systemic disease that could affect cognition.
Today, in addition to these traditional clinical criteria, the diagnosis of Alzheimer’s relies increasingly on biomarkers, which makes it possible to detect the disease with greater precision, even in early stages.
Current biomarkers
For years, the study of cerebrospinal fluid and amyloid or tau PET were the main biological tools. Today, one of the most relevant advances is the development of blood biomarkers, especially p-Tau217, which has proved highly useful for detecting Alzheimer’s pathology with a far less invasive technique.
In simplified terms, diagnosis today can combine:
- Clinical and neuropsychological assessment
- Structural neuroimaging
- Amyloid biomarkers
- Tau biomarkers
- Markers of neurodegeneration and inflammation
This has changed the diagnostic approach, moving from a purely clinical model to a clinical-biological one.
Prognostic factors
The prognostic factors for this disease include:
- Visuospatial impairment
- Extrapyramidal signs
- Psychosis and depression
- Initial severity and functional disability
- Malnutrition, diabetes mellitus, lack of physical exercise and cardiovascular disease
To these factors is added the fact that the early presence of behavioural changes, marked apathy, severe disorientation or motor symptoms is usually associated with a faster course and greater functional dependence.
Treatment
Finally, as regards treatment, there is currently no drug that can cure Alzheimer’s disease or completely reverse the damage already done. However, we do have various therapeutic strategies that can relieve symptoms, slow progression in certain cases and improve quality of life.
Symptomatic pharmacological treatment
The treatments most used in early and moderate stages are acetylcholinesterase inhibitors, such as:
- Donepezil
- Rivastigmine
- Galantamine
These drugs help to maintain cognitive function for longer in some patients.
In moderate and severe stages, memantine may also be used; it acts on the glutamatergic system and may help to partially stabilise symptoms.
New disease-modifying therapies
In recent years, treatments targeting beta-amyloid have emerged, such as lecanemab and donanemab, indicated in very early stages of the disease and in carefully selected patients. These treatments do not restore lost function, but seek to modify the biological progression of Alzheimer’s.
Their use requires prior confirmation of amyloid pathology and close monitoring, since they can produce significant adverse effects, especially changes detectable on magnetic resonance imaging.
Non-pharmacological interventions
The approach to Alzheimer’s must not focus on medication alone. Non-pharmacological interventions are essential and must be tailored to each person. The most useful include:
- Cognitive stimulation
- Occupational therapy
- Adapted physical exercise
- Maintaining routines
- Music therapy
- Adapting the environment
- Emotional support and psychoeducation for relatives
It has also been seen that good nutrition, the prevention of dehydration and the treatment of problems such as dysphagia are key in advanced stages.
Family and social impact
Alzheimer’s does not affect only the person who has it. It also has a strong impact on carers and on the family. Much of the economic and emotional cost of the disease falls on those close by, who usually take on daily care for years.
Carer burden is very frequent, especially when behavioural changes, physical dependence or sleep disorders appear. For this reason, support for the carer, access to support groups and psychosocial intervention are an essential part of comprehensive treatment.
Conclusion
Alzheimer’s disease is a complex, progressive and multifactorial neurodegenerative condition. Although it begins slowly, its advance profoundly affects the person’s memory, language, behaviour, functioning and independence.
Today we know that it is not only a clinical picture, but a biological process that can begin many years before the symptoms. Advances in biomarkers, especially in blood, and the development of new therapies are changing the way the disease is diagnosed and managed. Even so, prevention, early diagnosis, comprehensive care and support for families remain fundamental pillars.
