A Growing Public Health Challenge
Neurocognitive disorders (NCDs) encompass conditions that cause progressive decline in memory, cognition, and behaviour, ultimately leading to loss of independence.
Dementia is the terminal stage of these disorders, and its prevalence is rising rapidly, with Alzheimer’s disease (AD) as the most frequent cause.
Epidemiological projections estimate that the global prevalence of AD in individuals aged 65+ will quadruple by 2050. Currently, between 5.5% and 9% of the general population is affected. The socioeconomic impact is substantial, both for healthcare systems and for patients and their families.
Alzheimer’s Disease
AD is a neurodegenerative disorder defined by a spectrum of clinical and biological features:
Clinical progression from short-term memory loss and executive dysfunction to language deficits, behavioural changes, and eventual complete dependency.
Pathological hallmarks include amyloid-β plaques and neurofibrillary tangles of phosphorylated tau, alongside downstream processes such as inflammation, synaptic dysfunction, and neuronal loss.
The disease follows a continuum:
- Preclinical AD: accumulation of pathology in the absence of symptoms.
- Mild Cognitive Impairment (MCI): subtle but measurable decline, often a precursor to dementia.
- Dementia: overt cognitive and functional impairment.
Approximately 10% of adults over 45 report subjective cognitive decline, which may represent an early indicator of disease.
Other Relevant Disorders
The biomarker-based diagnostic approach also applies to a range of non-Alzheimer’s dementias and atypical syndromes, including:
Frontotemporal lobar degeneration (FTLD).
Lewy body disease (LBD).
Motor tauopathies such as corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP).
Cognitive impairment without a clear diagnostic hypothesis.
These conditions often overlap clinically with Alzheimer’s disease, highlighting the importance of accurate biomarker-based differentiation.
The Role of Biomarkers and Nuclear Medicine
While initial diagnosis relies on history, neurological examination, cognitive testing, structural imaging, and laboratory studies, these tools alone are insufficient for reliable differential diagnosis.
Biomarker-based methods, particularly nuclear medicine imaging, provide essential added value:
FDG-PET: reveals patterns of cortical hypometabolism supporting syndrome differentiation.
Amyloid PET: detects β-amyloid deposition in vivo, confirming or excluding AD pathology.
DaT-SPECT and MIBG scintigraphy: aid in the diagnosis of Lewy body disease and Parkinsonian dementias.
Why Early and Accurate Diagnosis Matters
A timely biomarker-based diagnosis has far-reaching benefits:
Therapeutic impact
access to the first FDA-approved disease-modifying therapies for AD (currently under EMA review).
Clinical management
optimised use of pharmacological and non-pharmacological interventions, improved handling of behavioural and psychiatric symptoms.
Research opportunities
eligibility for clinical trials and novel therapeutic approaches.
Patient safety
prevention of iatrogenesis through avoidance of ineffective or inappropriate treatments.
Socioeconomic benefits
patients and families can make informed decisions about care, lifestyle, and planning — the so-called “value of knowing.”
The European Framework
In 2024, a consortium of 22 experts from 11 European scientific societies published intersocietal recommendations for the biomarker-based diagnosis of NCDs. This consensus defined:
First-line and second-line testing strategies according to patient profiles.
Integration of biomarkers, including molecular imaging, into routine diagnostic workflows.
A pathway to greater consistency in diagnostic practice across Europe.