Comparing Prodromal Dementia with Lewy Bodies, Prodromal Alzheimer’s Disease, and Parkinson’s Disease

Distinguishing between different types of dementia can be crucial for effective management and care. Prodromal stages of dementia, where symptoms are not yet fully developed, present a unique challenge for physicians. Two of the most common forms of dementia include Dementia with Lewy Bodies (DLB) and Alzheimer’s Disease. (AD). Prodromal dementia refers to the earliest stages of cognitive decline, where symptoms are beginning to present, but are not severe enough to meet the criteria for dementia diagnosis. Recognizing prodromal symptoms allows for early intervention and can potentially alter disease progression.

DLB is characterized by the presence of Lewy bodies: abnormal protein deposits in the brain. Based on clinical presentation alone, prodromal DLB is often mistakenly diagnosed as other dementias. pDLB often presents itself as fluctuations in cognition, hallucinations, and rapid eye movement sleep behavior disorder (RBD). Late onset of these psychiatric symptoms can alert physicians to possible DLB. RBD is a key feature of pDLB and can occur years before other symptoms making it an important consideration for those performing diagnosis. Additionally, many patients experience parkinsonism features including tremors, bradykinesia, and gait disturbances. DLB is diagnosed when cognitive impairments precede parkinsonism or appear within a year of parkinsonism. Parkinson’s Disease with Dementia (PDD) is diagnosed when parkinsonism precedes cognitive impairments. Both are Lewy-body diseases. Apathy and depression are more commonly seen in pDLB than in prodromal AD and tend to be more severe. Olfactory dysfunction is also seen more often with early DLB pathology than AD.

pAD on the other hand is marked by the accumulation of amyloid-beta plaques and tau tangles in the brain. Common symptoms include progressive memory impairment, language difficulties, and issues with executive functioning. A major difference between the two dementias is that parkinsonism features typically do not manifest in pAD as they do in pDLB, although some motor impairments may emerge as the disease progresses. Biomarkers for amyloid beta and the presence of two copies of APOE4 (e4/e4) are highly associated with pAD over pDLB. pAD is often referred to as Mild Cognitive Impairment (MCI), although MCI does not necessarily progress to AD. Unlike pAD, other components of pDLB are not present in MCI, therefore MCI with Lewy bodies and pDLB are less likely to be used synonymously.

Diagnosing pDLB versus pAD requires comprehensive assessment. This can include a combination of history, neuropsychological testing, neuroimaging (such as MRI, PET, and DaT scans), and biomarker analysis (CSF and blood-based biomarkers). Unfortunately, the clinical symptom overlap between these two dementias can make diagnosis complicated, especially in the prodromal stage of the disease. This makes careful analysis of symptoms and disease changes essential. Based on autopsy analysis, it is quite common to have co-pathology of DLB and AD as opposed to a pure form of either disease which can complicate treatment, especially in later stages.

Accurate diagnosis of pDLB versus pAD, or a mixed disease of both is essential for tailoring treatment strategies and providing appropriate support to patients and their families. While research into improving disease-modifying therapies for both conditions is ongoing, symptomatic management and non-pharmacological interventions can improve quality of life and mitigate distressing symptoms. Recognizing differences and diagnosing early is also vital as disease-modifying therapies progress in clinical trials. By distinguishing between pDLB and pAD, physicians can create more personalized and effective patient care.

As pDLB and pAD have different pathologies despite similarities in their symptoms, accurate diagnosis is important for tailoring treatment strategies and providing appropriate support for patients and their families or caregivers. Given the difficulties in differentiating clinical symptoms, biomarkers can be incredibly helpful in early assessment, especially for AD. Common biomarkers include imaging (MRI, PET, etc.), CSF, and blood tests. Biomarkers are already frequently used in research and growing in clinical use. Unfortunately, biomarkers may not present a clear diagnosis of DLB as many features of DLB are clinical. Imaging biomarkers or CSF can rule out other diseases such as AD, but do not necessarily diagnose DLB as they lack either specificity or sensitivity. Research is ongoing to find better methods of specific DLB diagnosis including promising efforts in EEG and blood biomarkers.



Abdelmoaty, M.M., Lu, E., Kadry, R., Foster, E.R., Bhattarai, S., Mosley R.L., & Gendelman, H.E. (2023). Clinical biomarkers for Lewy body diseases. Cell Bioscience, 13(209).

Bousiges O. & Blanc F.  (2022). Biomarkers of Dementia with Lewy bodies: Differential diagnostic with Alzheimer’s disease. International Journal of Molecular Sciences, 23(12).

Wyman-Chick, K. A., Chaudhury, P., Bayram, E., Abdelnour, C., Matar, E., Chiu, S. Y., … & Kane, J. P. (2024). Differentiating prodromal Dementia with Lewy Bodies from prodromal Alzheimer’s Disease: a pragmatic review for clinicians. Neurology and Therapy, 1-22.