Challenges and opportunities in early diagnosis and prevention

Mixed dementia etiologies, and neuropsychiatric symptoms that overlap cognitive deficits illustrate challenges in the diagnosis of Alzheimer’s Disease, while rapid advances in plasma biomarkers and evidence that disease onset can be delayed are positive developments.

Part of the challenge of Alzheimer’s Disease is that patients often have mixed-pathology dementias, Dennis Selkoe (Brigham and Women’s Hospital, Boston, USA) told a symposium at ADPD 2021 Virtual.

Although AD accounts for 60-70% of dementias,1 vascular dementia – the second most frequent form of the disorder -- is present in over 30% of people with AD.2 And over 50% of people with vascular dementia may exhibit AD-like pathology.2

Mixed vascular and Alzheimer pathology is frequent and adversely affects prognosis


Overlapping and exacerbating pathologies

This is not a benign intertwining of comorbidities since mixed pathology may triple the risk that dementia will develop when compared with people in whom only one pathology is present.3

Another challenge in diagnosis and management is the wide range of neuropsychiatric symptoms common in people with AD, even in very early and prodromal phases of mild cognitive impairment,4-6 Miia Kivipelto (Karolinska Institute, Stockholm, Sweden) reported.

The nature and severity of neuropsychiatric symptoms vary between individuals and over the course of disease and may remit spontaneously. But they typically have a severe impact on quality of life, progression, caregiver burden, and rate of institutionalization.4-6

Neuropsychiatric symptoms complicate the clinical picture

Examples include apathy, irritability, anxiety and depression, agitation, aggression and sleep-wake disturbance. Aberrant motor behaviors such as picking and pacing are frequent, and some patients with AD demonstrate paranoid delusions and reduplicative paramnesias.

Patients with mixed AD and Lewy body dementia tend to exhibit more severe neuropsychiatric symptoms,7 including hallucinations and delusions, Professor Kivipelto said.


Biomarkers and FINGER point in the right direction

On a more positive note, speakers predicted that within 3-5 years (and perhaps 1-2 years if we are being really optimistic), plasma biomarkers for phosphorylated tau and its various epitopes and fragments will enable widespread screening for patients with AD, even in primary care.  And such markers also look capable of predicting rate of cognitive decline.

Multidisciplinary intervention improves cognition outcomes

A second reason for cautious optimism is the demonstration that the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER), which involves cognitive training, dietary advice, encouragement of physical exercise and comprehensive management of vascular risk factors, leads to improved executive function, processing speed and memory when compared with a control group.8

This encouraging evidence that prevention of dementia, or at least its delay, is possible has recently been reinforced by evidence that a nutritional intervention (LipiDiDiet) can reduce the rate of cognitive decline and brain atrophy in people with mild cognitive impairment due to AD.9


The symposium was supported by Biogen

Our correspondent’s highlights from the symposium are meant as a fair representation of the scientific content presented. The views and opinions expressed on this page do not necessarily reflect those of Lundbeck.


1. World Health Organisation. Dementia. September 21, 2020

2. Jagtap A et al. Biomarkers and Genomic Med 2015;7:43-56

3. Rahimi J, Kovacs GG. Alzheimers Res Ther 2014;6:82

4. Lyketsos CG. Alzheimers Dementia 2011;7:532-9

5. Lyketsos CG. J Prev Alzheimers Disease 2015;2:155-6

6. Ismail Z et al. J Alzheimers Dis 2016;12:195-202

7. Chung EJ et al. JAMA Neurol 2015;72:789-96

8. Ngandu T, et al. Lancet 2015; Jun 6;385:2255-63

9. Soininen H et al. Alzheimers Dementia 2021;17:29-40

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