Alzheimer's disease is often known for the memory loss experienced by patients. It is a progressive disease that generally begins with an isolated, progressive amnesic syndrome, unknown to the patient. Gradually, language disorders (aphasia), writing disorders (dysgraphia), movement disorders (apraxia) and loss of the ability to recognise objects and faces (agnosia) set in.
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The diagnosis of Alzheimer’s disease is based on :

  • A clinical examination to assess the patient’s cognitive functions and behaviour using specific tests.
  • MRI (Magnetic Resonance Imaging), which shows a loss of volume in the hippocampus, the region of the brain essential for memory, and/or other regions of the brain.
  • PET (Positron Emission Tomography) with glucose, to visualise cerebral metabolism during the course of the disease
  • Analysis of the CSF (cerebrospinal fluid) that circulates around the brain and in the central canal of the spinal cord, obtained by lumbar puncture. Variations in the concentration of two molecules measured in this fluid, amyloid protein and tau protein, are characteristic of Alzheimer’s disease.

Doctors and researchers have traditionally distinguished four stages of Alzheimer’s disease:

  • The stage of mild cognitive impairment: symptoms such as memory problems are measurable but have little or no impact on daily life.
  • The ‘mild dementia’ stage. Dementia is a medical term that simply means that the symptoms have an impact on the autonomy of the patient, who needs help to carry out at least one significant everyday task that he or she used to do alone (for example, paying bills). It therefore has a different meaning to the term dementia used in everyday language. At this stage, the symptoms are more marked than they were initially and begin to disable the patient. The disease may also have begun to spread and affect other functions such as behaviour, language and vision, as well as causing greater memory loss. Patients require assistance with certain daily activities.
  • The so-called “moderate dementia” stage. At this stage, the disease has spread and more clearly affects other cognitive functions, as well as causing greater memory loss. At this stage, patients need help with several daily activities.
  • The so-called “severe dementia” stage: Short- and long-term memory is severely affected. Other cognitive functions are also severely affected. Patients are no longer independent in their daily lives and require assistance with basic tasks.

There is currently no effective treatment to halt the advance of Alzheimer’s disease or cure it. Our knowledge of its mechanisms is still very incomplete. We know that biomarkers can identify the disease before the first clinical signs appear, thanks for example to recently identified potential blood markers, but early diagnosis of Alzheimer’s remains difficult for practitioners. And by the time symptoms do appear, and patients have had the disease for several years, it is often too late to take effective action to counter the progression of Alzheimer’s disease. Research into Alzheimer’s disease and its early stages is therefore vital, so that we can intervene as early as possible and be in a position to develop new treatments.

The INSIGHT cohort, monitored at the Institut de la mémoire et de la maladie d’Alzheimer by Prof. Bruno Dubois’ clinical research team, is one of the first in the world to follow nearly 320 healthy subjects at risk with the aim of identifying the factors that trigger Alzheimer’s disease. The initial results of this study, published in early 2018, show that at 30 months’ follow-up, the presence of amyloid lesions has no impact on the cognition and behaviour of subjects who carry them. They suggest the existence of compensatory mechanisms in subjects with these lesions. However, the subjects who showed signs of Alzheimer’s disease during their follow-up were all carriers of these lesions. This cohort is enabling researchers at the Institut du Cerveau to develop studies with the aim of identifying cerebral ‘anomalies’ predictive of Alzheimer’s disease, i.e. dysfunctions in the brain more than 10 years before the onset of symptoms and the diagnosis of Alzheimer’s disease.


At the Paris Brain Institute


Sinead Gaubert, neurologist and researcher at the Brain Institute (CNRS/Inserm/Sorbonne University) at the Pitié-Salpêtrière Hospital, Federico Raimondo (University of Liège/Sorbonne University) and Stéphane Epelbaum, neurologist, have used electroencephalography (EEG) to identify early cerebral electrical changes in subjects in the preclinical phase of Alzheimer’s disease, as part of the INSIGHT-preAD cohort. These extremely promising results suggest that EEG could be used in the coming years to detect preclinical Alzheimer’s disease at an early stage.


At the Paris Brain Institute, Lara Migliaccio’s group in Richard Lévy’s team is studying vulnerability and resilience to disease, particularly in young subjects, and the extent to which functional neuronal networks respond to pathological damage. The aim is to understand what steers patients towards a pathology that is more focal and less progressive or, on the contrary, very diffuse with a much more severe course, and to identify the individual characteristics of subjects that play a role in the disease, such as sleep quality, lifestyle, diet and activities of varying degrees of intellectual ability, in order to obtain an individual-scale measure of what is known as cognitive reserve. The challenge of the project is to follow patients, possibly over several years, and to highlight the basal characteristics that predict their evolution over two years, and to extract concrete measurements to build an algorithm for the personalised evolution of patients.