A general practice-centred model for early diagnosis and management of Alzheimer’s disease in Denmark: rationale, evidence and a pragmatic diagnostic approach

Abstract

Purpose

Alzheimer’s disease is a leading cause of disability among older adults and poses increasing challenges for healthcare systems. In Denmark, demographic changes and healthcare reform are driving greater involvement of primary care in diagnosis and management.

Materials and methods

This paper examines the rationale for a general practice-centred model and summarises recent diagnostic developments, including blood-based biomarkers.

Results

Although current disease-modifying therapies show only modest benefit, ongoing research and scalable biomarkers enable earlier and more accessible diagnosis. We propose a pragmatic three-step diagnostic approach for primary care, with structured clinical and cognitive assessment, exclusion of secondary causes including structural neuroimaging, and in the near future, the availability of feasible biomarkers to support diagnosis and guide referral. We also outline key organisational, educational and ethical requirements for implementation.

Conclusion

A general practice-centred model may improve diagnostic timeliness, accessibility and continuity of care if integrated within a robust clinical and ethical framework.

Introduction

Alzheimer’s disease accounts for approximately 60–80% of dementia cases worldwide and remains a leading cause of disability and death among older adults [1]. Pathologically, the disease is mainly characterised by extracellular deposition of amyloid-β (Aβ) plaques and intracellular neurofibrillary tangles composed of hyperphosphorylated tau protein [2]. Once symptomatic, Alzheimer’s disease typically follows a progressive course marked by cognitive decline, functional impairment, behavioural symptoms and increasing dependency.

Dementia imposes a substantial burden on individuals, families and healthcare systems [1]. Informal caregivers frequently experience considerable psychological, physical and financial strain, while municipalities and national health services must absorb rising costs related to home care services, long-term care and institutionalisation. Because prevalence increases steeply with age, demographic changes across Europe, including Denmark, are expected to place increasing pressure on health and social care systems in the coming decades [1]. Without strategic reorganisation and expansion of healthcare capacity, the growing burden risks compromising quality of care for this vulnerable population and their families.

This challenge is recognised globally, and healthcare systems in several countries have begun reconsidering how diagnostic pathways and treatment strategies for cognitive decline are organised, acknowledging that specialist-centred models alone may be insufficient [3]. Scandinavian studies have demonstrated that structured dementia diagnostic programmes in primary care can substantially increase case identification and support a diagnostic evaluation led by general practitioners (GPs) [4,5].

Until recently, the etiological diagnosis of dementia and decisions regarding disease-modifying therapies (DMTs) have largely been handled by neurological and psychiatric departments [6]. Diagnostic confirmation has relied on clinical assessment combined with laboratory testing, cerebrospinal fluid (CSF) analysis and neuroimaging. However, the emergence of blood-based biomarkers and the development of DMTs create new possibilities for earlier, clinically meaningful and scalable diagnostic processes.

In Denmark, ongoing healthcare reform explicitly envisions transferring a larger share of diagnostic and management responsibility for patients with cognitive symptoms to general practice, supporting a transition towards a general practice-centred model of care [7]. However, achieving such a shift requires more than simply reallocating resources and workforce capacity. It also necessitates transfer of and, in some cases, redesign, of competencies from secondary to primary care.

Such structural transitions require careful planning and pilot testing. Ensuring high-quality future care will require targeted education in risk communication, diagnosis, interpretation of emerging biomarkers, treatment initiation and palliative care within general practice [8]. Strengthened consultation opportunities between primary and secondary care will also be necessary. These initiatives should build upon the substantial clinical experience already present in Danish primary care while integrating rapidly expanding scientific knowledge in Alzheimer’s disease diagnostics and therapeutics.

This paper examines the opportunity and necessity of establishing a general practice-centred model for early diagnosis and longitudinal management of Alzheimer dementia. We analyse how recent diagnostic and therapeutic advances enable a decentralised GP-centred model of care and propose a pragmatic diagnostic approach for primary care alongside clearly defined referral criteria. Finally, we outline the educational, organisational and structural initiatives required to ensure quality, safety and sustainability.

Emerging opportunities in Alzheimer dementia diagnosis and treatment

For decades, the etiological diagnosis of Alzheimer’s disease has largely been confined to specialist memory clinics, as confirmation required either CSF analysis or advanced neuroimaging such as computed tomography (CT), magnetic resonance imaging (MRI) or positron emission tomography (PET). Consequently, early diagnosis has often been delayed, and specialist services have borne most of the diagnostic workload.

The validation of blood-based biomarkers may now challenge this traditional model. Plasma biomarkers capable of detecting Alzheimer’s pathology with high accuracy have emerged. Phosphorylated tau isoforms, particularly p-tau217, and the Aβ42:Aβ40 ratio show strong concordance with CSF and PET measures [9,10]. In a landmark multicentre study, Palmqvist et al. [11] demonstrated that predefined plasma biomarker thresholds achieved high diagnostic accuracy in both primary and secondary care settings. Importantly, diagnostic performance remained robust in real-world, non-specialist populations. Similarly, Barthélemy et al. [12] reported that new blood tests performed as well as, and in some cases better than, traditional CSF tests in detecting amyloid pathology. Furthermore, recent studies have shown that dried capillary plasma samples obtained through minimally invasive finger-prick methods closely match venous blood results for key Alzheimer biomarkers, particularly p-tau217, and accurately predict CSF positivity [13]. These findings support the integration of capillary blood-based biomarkers as scalable tools within routine diagnostic workflows.

Economic modelling further supports this shift. Incorporating blood-based biomarkers into diagnostic pathways can improve cost-effectiveness by reducing unnecessary advanced imaging and specialist consultations [14]. However, continued attention is required to ensure assay standardisation and address inter-laboratory variability [15].

Implementation research has also demonstrated that structured early-detection workflows embedded in primary care significantly improve identification rates of cognitive impairment [16]. Moreover, surveys indicate that many GPs are willing to adopt blood-based biomarker testing provided that adequate training, reimbursement structures and clear referral pathways are established [17]. Together, these developments render early Alzheimer dementia diagnosis scalable in ways previously unattainable.

While earlier evidence suggested that DMTs might offer greater benefit when initiated in early stages such as mild cognitive impairment or early dementia [18], concerns have been raised about the underrepresentation of certain patient groups, particularly frail older adults, in clinical trials, which may limit generalisability and temper expectations regarding their real-world impact [19]. A recent Cochrane review further indicates that the clinical benefits of these therapies are, at most, modest [20]. Nevertheless, substantial research efforts are ongoing, with new therapeutic candidates currently under investigation.

Persistent underdiagnosis and system constraints

Despite increasing awareness, early-stage Alzheimer’s disease remains substantially underdiagnosed. Detection rates of mild cognitive impairment in U.S. primary care have been estimated at approximately 8% [21]. European studies similarly suggest that only around one-third of individuals receive a diagnosis during the mild cognitive impairment stage [22–24].

Several factors contribute to delayed diagnosis. Memory complaints are often normalised as part of aging, stigma surrounding dementia persists and limited consultation time may reduce opportunities for comprehensive cognitive assessment. Historically, the absence of DMTs also contributed to therapeutic nihilism. Specialist capacity represents an additional bottleneck. Modelling studies suggest that specialist-only diagnostic pathways will struggle to meet future demand if biomarker-based testing becomes widely implemented [3]. In practice, a considerable proportion of dementia diagnoses already occur outside specialist settings [25].

A decentralised, general practice-centred model can strengthen early detection and coordinates ongoing management including secondary prophylaxis, while specialist services focus on complex cases, treatment initiation of newly registered medicamentation, and advanced diagnostics. Such a shift may also improve equity of access and better align care delivery with demographic realities.

Repositioning general practice in dementia care

Danish general practice is well positioned to serve as the central coordinating setting in a general practice-centred model of dementia care for patients with Alzheimer’s disease. GPs already manage large numbers of older adults with multimorbidity, neurovascular disease and cognitive complaints as part of routine clinical practice [7]. Frequent contact with older people enables continuity of care characterised by person-centred knowledge and mutual trust [26]. This ongoing relationship allows GPs to detect subtle behavioural changes or declines in social and psychological functioning long before they become measurable in standardised psychometric tests.

Courses in geriatric medicine and cognitive impairment are already incorporated into mandatory continuing medical education programmes for Danish GPs [27,28]. Building on these existing competencies through targeted training initiatives and structural adjustments is therefore feasible. The expansion of primary care responsibility for Alzheimer’s disease diagnostics raises important ethical considerations. A key question is who should be assessed, and according to which criteria. Opportunistic screening may increase detection but also risks overdiagnosis, uncertainty and psychological harm, particularly given the limited therapeutic benefit of current treatments. The growing use of biomarker-based diagnostics in asymptomatic or minimally symptomatic individuals further raises concerns regarding informed consent and the management of uncertain findings. Clear ethical guidance is therefore needed. Establishing a pragmatic framework for case finding, incorporating risk stratification, patient preferences and proportionality between benefit and harm, would strengthen a GP-centred diagnostic model and help ensure meaningful patient benefit.

A pragmatic three-step diagnostic approach for primary care

A structured three-step diagnostic process could operationalise Alzheimer detection in Danish primary care: (a) structured clinical and cognitive assessment, including history from both patient and informant, cognitive testing, depression screening, medication review and functional evaluation; (b) exclusion of other causes of dementia and structural imaging, including relevant laboratory testing and neuroimaging; and (c) in a near future consideration of blood-based biomarker testing, in cases with persistent suspicion of neurodegenerative disease (Table 1). The development of biomarkers is progressing rapidly in terms of both clinical relevance and accessibility [13].

Table 1.

A pragmatic three-step primary care process.

Step 1: Structured clinical and cognitive assessment Indications: Cognitive complaints, functional decline or informant concern. This diagnostic approach is intended for case finding in symptomatic individuals. Components: Detailed medical and medication history (including caregiver input) Screening for depression and psychiatric disorders Physical and neurological examination Standardised cognitive testing (e.g. BASIC, MMSE, MoCA) Functional assessment Typical early Alzheimer dementia pattern: Impaired episodic memory with poor recall despite cueing and gradual functional decline. Step 2: Exclusion of secondary causes and structural imaging Purpose: Rule out reversible and identify alternative or mixed pathology. Laboratory tests: TSH, vitamin B12, complete blood count, metabolic panel Medication review Consider alcohol or drug abuse Cerebral imaging based on regional recommendations (e.g. MRI or CT). Essential for excluding structural and vascular causes of cognitive decline (e.g. tumours, subdural hematoma, normal pressure hydrocephalus, cerebrovascular disease) Typical Alzheimer dementia pattern: Normal laboratory results and medial temporal lobe atrophy on imaging. Step 3: In a near future, blood-based biomarker testing Indications: Persistent suspicion of neurodegenerative disease. Use of biomarkers should be accompanied by appropriate pre- and post-test counselling, including discussion of diagnostic uncertainty and potential psychological implications. Plasma p-tau isoforms Plasma Aβ42:Aβ40 ratio Purpose: Stratify likelihood of Alzheimer dementia pathology Guide targeted specialist referral Inform eligibility for disease-modifying therapy

Referral to specialist care should be reserved for selected cases requiring additional expertise. These include individuals with unexplained long-lasting cognitive decline and inconclusive biomarker results, atypical clinical presentations, unusually rapid disease progression or complex neuropsychiatric comorbidities. Referral is also appropriate when confirmatory CSF analysis or PET imaging is required, or when consideration or initiation of DMTs necessitates specialist supervision. Clear and flexible patient pathways are essential to ensure that referrals are neither rejected nor unnecessarily delayed [29].

Longitudinal management of diagnosed dementia in general practice

These patients often have a long-standing trajectory in general practice before a dementia diagnosis is established. Once alternative causes have been excluded, general practice is well suited to continue long-term management. The structure of Danish primary care supports continuity across the disease trajectory and facilitates coordinated care.

Primary care teams can monitor cognitive trajectories, optimise vascular risk factors, manage polypharmacy, address behavioural and psychological symptoms, support caregivers, and facilitate advance care planning. Such an approach may reduce fragmentation of care and improve coordination across health and social care services [30]. Importantly, a GP-centred model may also strengthen equity of access in rural areas where specialist services are less readily available [31]. A long well-established collaboration between general practice and municipality homecare is no doubt of significant importance for this patient group.

Implementation challenges and educational requirements

Despite these opportunities, several important barriers must be addressed before more dementia diagnosis and management can be shifted to primary care. Many GPs report low confidence in communicating early dementia diagnoses and in interpreting biomarker results [32]. Targeted educational programmes for primary care are therefore essential. These should build on existing GP competencies rather than replicate specialist hospital training and should be based on identified educational needs in general practice.

Organisational changes will also be needed. Consultation time and reimbursement systems must allow for longer diagnostic consultations and follow-up visits. The 2024 European intersocietal recommendations [33] and the 2025 Alzheimer’s Association Clinical Practice Guideline [34] provide an evolving scientific framework for the clinical use of blood-based biomarkers. But these need to be adapted to the Danish primary care setting. General practice should work closely with neurologists and medical biochemists to conduct feasibility and validation studies in Denmark and other countries moving towards primary care-based dementia management. Overall, successful implementation will depend on addressing key system factors, including education, reimbursement structures, biomarker standardisation and clear referral pathways.

Conclusions

The evolving landscape of Alzheimer’s disease diagnosis represents a pivotal moment in dementia care. Although current DMTs have not yet demonstrated clear and consistent clinical benefit, ongoing research continues to explore more effective therapeutic options. At the same time, accessible blood-based biomarkers are creating new opportunities for scalable and less invasive diagnostic pathways. Together and urged by demographic development, these developments support the implementation of a general practice-centred model for Alzheimer’s disease diagnosis and management.

Successful implementation of a general practice-centred model for Alzheimer’s disease will require targeted educational initiatives, clearly defined referral pathways, appropriate reimbursement structures and robust quality assurance systems. With these elements in place, Danish general practice can play a leading role in earlier detection and longitudinal management of Alzheimer’s disease across the care continuum. The sustainability of future Alzheimer’s care will depend not only on progress in specialist treatments, but also on the ability of primary care to integrate and deliver new diagnostic and therapeutic advances in a safe, equitable and effective manner.

Ethical approval

No persons nor person related data have been enrolled in this article.

Consent form

Not applicable.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

Not applicable.