Stages of Alzheimer’s disease

First signs

Alzheimer’s disease can only be diagnosed by a doctor, though there are definitely symptoms that should be taken seriously. Generally speaking, there are ten warning signs of Alzheimer’s disease :

1. Memory loss that disrupts daily life
2. Problems with planning and solving problems
3. Problems with carrying out familiar tasks like getting dressed or eating
4. Disorientation regarding place and time
5. Problems with judging visual input
6. Problems finding the desired word in speech and writing
7. Repeatedly mislaying things
8. Poor ability to make judgements
9. Withdrawal from social activities and family interactions
10. Mood and personality changes

Which symptoms occur and how severe they are varies from person to person. It also depends on which stage of dementia a person is in.

The 3 or 7 stages of Alzheimer’s disease

Doctors agree that there are several stages of Alzheimer’s disease. Two models have been circulated for classification, and there are considered to be three or seven dementia stages, depending on the model.

The 3-stage model

According to this model, Alzheimer’s disease generally progresses in three stages of dementia[1]. It is assumed here that the individual stages of Alzheimer’s disease last for around three years on average.

1. Early stage: mild dementia
In the early stage of Alzheimer’s disease, there are only slight limitations to independent living. Affected patients only require support with demanding tasks.

The primary symptom is forgetfulness (amnesia); things such as names or dates are forgotten.

While the disease manifests in various ways in different people, they may suffer from short-term memory disorders and problems with finding the desired word. The initial difficulties with everyday tasks and orientation to place and time will appear.

2. Middle stage: moderate dementia
In the middle stage of Alzheimer’s disease, there are already considerable limitations on independent living. Affected patients now also require support for simple tasks and are no longer able to care for themselves.

Primary symptoms include the loss of practical skills (apraxia ), loss of speech comprehension (Wernicke’s aphasia ) and difficulties in processing sensory input and when making decisions (agnosia ).

3. Late stage: severe dementia
In the late dementia stage, leading an independent life is no longer possible; patients require support in all activities.

The primary symptoms include confinement to bed, lack of interest, loss of appetite, incontinence and severe impairment of speech.

The 7-stage model

With this model, a more accurate assessment is made by means of screening by a doctor, based on the Reisberg scale or Global Deterioration Scale (GDS). This scale, developed by Dr Barry Reisberg, distinguishes between seven stages of dementia[2]. They range from normal healthy condition through to the final stage of Alzheimer’s disease.

Stage 1: Normal function
Normal functioning, no cognitive impairment.

Stage 2: Very mild cognitive impairment
Increasing forgetfulness sets in; at this point, it is difficult for even specialists to distinguish from normal forgetfulness.

Stage 3: Mild cognitive impairment
This is when problems emerge for the first time that are noticed by relatives. Initial difficulties with finding the desired word arise, or it may be the case that the person repeatedly asks the same question. Concentration and the ability to learn something new are affected. Affected people may tend towards depressive moods.

Stage 4: Onset of dementia
In this stage, a diagnosis of Alzheimer’s disease may be made with relative certainty. It is now also noticeable to people outside a person’s own circle that something more serious than old-age phenomena exists. Affected persons increasingly experience difficult with everyday tasks such as paying bills. They forget what happened recently or parts of their own past. Typical symptoms are a flattened emotional response, concealing shortcomings (including from themselves) and increased withdrawal from social life.

Stage 5: Moderate dementia
This stage roughly corresponds to Stage 2 in the 3-stage model. It is generally no longer possible to live alone and to manage everyday tasks. Affected persons are often no longer able to judge which clothing is appropriate for the weather. Orientation to place and time is also reduced, meaning that affected persons often no longer know where they are, where they live, or what season or what month it is, for example. They often no longer recognise friends and relatives and large gaps start to appear in remembering events in their own life. In many cases, rage and mistrust are exhibited. The person becomes increasingly withdrawn. This phase lasts around 18 months on average.

Stage 6: Severe dementia
In this stage, affected persons experience symptoms that correspond to the end of Stage 2 of the 3-stage model: They require assistance even for the simplest of everyday tasks such as eating or dressing and undressing, they no longer recognise even close relatives such as children, siblings or their partner, and significant personality changes may occur. Typical symptoms of this stage are mistrust and hallucinations, as well as wandering and emotional changes such as aggressiveness. The sleep-wake rhythm is disrupted and the person may suffer from incontinence.

Stage 7: Very severe dementia
In this final, advanced stage of Alzheimer’s disease, the person requires 24-hour care, as they are no longer able to manage everyday tasks alone. Affected persons are usually no longer able to walk and over time are no longer able to sit upright or hold their head up. The ability to smile and to speak is also lost.

How to diagnose Alzheimer’s disease

While dementia is relatively obvious in a later stage, it is not always easy at the start to distinguish between mild normal phenomena of ageing and the onset of dementia. In addition, not every form of dementia is Alzheimer’s disease. A differential diagnosis requires medical cognition tests and increasingly biomarkers.

Cognition tests
Doctors use a series of short tests[3] to determine the extent of a person’s illness with dementia. These tests may also indicate the type of dementia that the person has and are used to assess the progression of the disease. The tests must be performed by specialists and evaluated in conjunction with medical interviews and examinations, in order to rule out other causes of symptoms, such as underlying physical or psychiatric illnesses or medicines. Widely used tests include the »clock-drawing test«, the »MoCa« (Montreal Cognitive Assessment), the »DemTect« (Dementia Detection Test) and the »Mini Mental State Examination« (MMSE).

Clock-drawing test
In this simple test, patients have to draw the face of a clock and show a time on it. The assessment not only takes account of the accuracy of the drawing, but also hesitation or the need for correction.

DemTect
This short five-part test assesses attention, recall ability and vocabulary. After memorising a list of words, figures have to be converted into words. This is followed by the »supermarket task«, in which the person has to list as many things as possible that can be bought in a supermarket. Finally, series of numbers have to be recalled backwards and the person is asked to recall the list of words read out in the first part.

MoCa
This test, which lasts around 10 minutes, is especially suitable for identifying dementia at an early stage. A person is given 30 questions that test aspects including language, memory, attention, behaviour, mental arithmetic, orientation, pattern recognition, word fluency and abstract thinking. The maximum possible score is 30 points. With a score below 26 points, at least a mild cognitive impairment may be assumed, while with score below 6 points indicates severe cognitive impairment.

MMSE
This test helps doctors to distinguish between depression, dementia and age-related forgetfulness. Patients are given set tasks as part of a structured interview:

• 10 questions on orientation to place and time
• Exercise on retentive memory with 3 terms
• 5 simple mental arithmetic tasks
• Recall of the 3 terms from the retentive memory test
• Language test with action tasks

One point is awarded for each correct word and a maximum possible score is 30 points. With a score of 20 to 27 points, a mild cognitive impairment is assumed, with less than 20 points a moderate cognitive impairment, and less than 10 points indicates severe dementia. If the MMSE indicates dementia, further examinations are carried for clarification, such as MRT (magnetic resonance tomography), CT (computed tomography) or PET (positron emission tomography). These provide information about any visible brain changes.

Biomarkers
Objectively measurable characteristics, such as laboratory values, which provide information about normal or pathological processes in the body are known as biomarkers. The last few years have seen significant advancements in this area in Alzheimer’s disease research. Certain proteins in cerebrospinal fluid (or »liquor«) or in the blood may provide indications for the correct diagnosis[4].

Liquor
To analyse biomarkers in cerebrospinal fluid, a lumbar puncture (spinal tap) in the region of the lumbar spine (L3/L4 or L4/L5) is required. The most important biomarkers for the diagnosis are beta-amyloid, which indicates the presence of amyloid plaques in the brain, and phosphorylated tau (p-tau) and total tau (t-tau). The latter values may indicate the degree of nerve cell degeneration.

Blood
These biomarkers are also present in the blood plasma. It has become clear, at least since the publication of new research results in July 2024,[5] that tests such as the (as yet not authorised) PrecivityAD2-Test (»APS2«), which indicated Alzheimer’s disease in the study with 90% accuracy, could be a reliable aid for diagnosis in the future.

Clarification instead of speculation

Considering the severe progression of the disease, fear of Alzheimer’s disease is all too understandable. Yet it is sensible to have any symptoms clarified with a doctor rather than worry if someone becomes forgetful. After all, even though there is currently no cure for Alzheimer’s disease, effective care in conjunction with various drug-based and non-drug-based therapies may slow down the course of the disease and alleviate symptoms. What is more, Alzheimer’s disease is already the subject of intensive research . Regardless of this, early diagnosis helps patients and their relatives to gain access to the help available and make plans for the future in good time.

References

1. Der Verlauf der Alzheimer-Erkrankung. Cited 2024; Available from: https://www.alzheimer-selbsthilfe.at/was-ist-demenz/der-verlauf-der-alzheimer-erkrankung].
2. Demenz Stadien. Cited 2024; Available from: https://www.alzheimer-deutschland.de/ueber-alzheimer-demenz/demenz-stadien].
3. Diagnostik von Alzheimer und anderer Demenzerkrankungen:
   Medizinische Demenz-Tests zur Diagnose. Cited 2024; Available from: https://www.alzheimer-forschung.de/alzheimer/diagnose/psychometrische-tests].
4. Hunter, T.R., et al., Alzheimer's disease biomarkers and their current use in clinical research and practice. Mol Psychiatry, 2024.
5. Barthelemy, N.R., et al., Highly accurate blood test for Alzheimer's disease is similar or superior to clinical cerebrospinal fluid tests. Nat Med, 2024. 30(4): p. 1085-1095.