Differentiating Prodromal Dementia with Lewy Bodies from Prodromal Alzheimer's Disease: A Pragmatic Review for Clinicians

Kathryn A Wyman-Chick¹, Parichita Chaudhury², Ece Bayram³, Carla Abdelnour⁴, Elie Matar⁵, Shannon Y Chiu⁶, Daniel Ferreira^{7

8

9}, Calum A Hamilton¹⁰, Paul C Donaghy¹⁰, Federico Rodriguez-Porcel¹¹, Jon B Toledo¹², Annegret Habich^{7

13}, Matthew J Barrett¹⁴, Bhavana Patel^{15

16}, Alberto Jaramillo-Jimenez^{17

18}, Gregory D Scott¹⁹, Joseph P M Kane²⁰

Affiliations

¹ Struthers Parkinson's Center and Center for Memory and Aging, Department of Neurology, HealthPartners/Park Nicollet, Bloomington, USA. kateawyman@gmail.com.
² Cleo Roberts Memory and Movement Center, Banner Sun Health Research Institute, Sun City, USA.
³ Parkinson and Other Movement Disorders Center, University of California San Diego, San Diego, USA.
⁴ Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Palo Alto, USA.
⁵ Central Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, Australia.
⁶ Department of Neurology, Mayo Clinic Arizona, Phoenix, USA.
⁷ Division of Clinical Geriatrics, Center for Alzheimer Research, Karolinska Institute, Solna, Sweden.
⁸ Department of Radiology, Mayo Clinic Rochester, Rochester, USA.
⁹ Facultad de Ciencias de la Salud, Universidad Fernando Pessoa Canarias, Las Palmas, Spain.
¹⁰ Translational and Clinical Research Institute, Newcastle University, Newcastle Upon Tyne, UK.
¹¹ Department of Neurology, Medical University of South Carolina, Charleston, USA.
¹² Nantz National Alzheimer Center, Stanley Appel Department of Neurology, Houston Methodist Hospital, Houston, USA.
¹³ University Hospital of Psychiatry and Psychotherapy, University of Bern, Bern, Switzerland.
¹⁴ Department of Neurology, Parkinson's and Movement Disorders Center, Virginia Commonwealth University, Richmond, USA.
¹⁵ Department of Neurology, College of Medicine, University of Florida, Gainesville, USA.
¹⁶ Norman Fixel Institute for Neurologic Diseases, University of Florida, Gainesville, USA.
¹⁷ Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway.
¹⁸ School of Medicine, Grupo de Neurociencias de Antioquia, Universidad de Antioquia, Medellín, Colombia.
¹⁹ Department of Pathology and Laboratory Services, VA Portland Medical Center, Portland, USA.
²⁰ Centre for Public Health, Queen's University Belfast, Belfast, UK.

PMID: 38720013
PMCID: PMC11136939
DOI: 10.1007/s40120-024-00620-x

Differentiating Prodromal Dementia with Lewy Bodies from Prodromal Alzheimer's Disease: A Pragmatic Review for Clinicians

Kathryn A Wyman-Chick et al. Neurol Ther. 2024 Jun.

. 2024 Jun;13(3):885-906.

doi: 10.1007/s40120-024-00620-x. Epub 2024 May 8.

Authors

Affiliations

¹ Struthers Parkinson's Center and Center for Memory and Aging, Department of Neurology, HealthPartners/Park Nicollet, Bloomington, USA. kateawyman@gmail.com.
² Cleo Roberts Memory and Movement Center, Banner Sun Health Research Institute, Sun City, USA.
³ Parkinson and Other Movement Disorders Center, University of California San Diego, San Diego, USA.
⁴ Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Palo Alto, USA.
⁵ Central Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, Australia.
⁶ Department of Neurology, Mayo Clinic Arizona, Phoenix, USA.
⁷ Division of Clinical Geriatrics, Center for Alzheimer Research, Karolinska Institute, Solna, Sweden.
⁸ Department of Radiology, Mayo Clinic Rochester, Rochester, USA.
⁹ Facultad de Ciencias de la Salud, Universidad Fernando Pessoa Canarias, Las Palmas, Spain.
¹⁰ Translational and Clinical Research Institute, Newcastle University, Newcastle Upon Tyne, UK.
¹¹ Department of Neurology, Medical University of South Carolina, Charleston, USA.
¹² Nantz National Alzheimer Center, Stanley Appel Department of Neurology, Houston Methodist Hospital, Houston, USA.
¹³ University Hospital of Psychiatry and Psychotherapy, University of Bern, Bern, Switzerland.
¹⁴ Department of Neurology, Parkinson's and Movement Disorders Center, Virginia Commonwealth University, Richmond, USA.
¹⁵ Department of Neurology, College of Medicine, University of Florida, Gainesville, USA.
¹⁶ Norman Fixel Institute for Neurologic Diseases, University of Florida, Gainesville, USA.
¹⁷ Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway.
¹⁸ School of Medicine, Grupo de Neurociencias de Antioquia, Universidad de Antioquia, Medellín, Colombia.
¹⁹ Department of Pathology and Laboratory Services, VA Portland Medical Center, Portland, USA.
²⁰ Centre for Public Health, Queen's University Belfast, Belfast, UK.

PMID: 38720013
PMCID: PMC11136939
DOI: 10.1007/s40120-024-00620-x

Abstract

This pragmatic review synthesises the current understanding of prodromal dementia with Lewy bodies (pDLB) and prodromal Alzheimer's disease (pAD), including clinical presentations, neuropsychological profiles, neuropsychiatric symptoms, biomarkers, and indications for disease management. The core clinical features of dementia with Lewy bodies (DLB)-parkinsonism, complex visual hallucinations, cognitive fluctuations, and REM sleep behaviour disorder are common prodromal symptoms. Supportive clinical features of pDLB include severe neuroleptic sensitivity, as well as autonomic and neuropsychiatric symptoms. The neuropsychological profile in mild cognitive impairment attributable to Lewy body pathology (MCI-LB) tends to include impairment in visuospatial skills and executive functioning, distinguishing it from MCI due to AD, which typically presents with impairment in memory. pDLB may present with cognitive impairment, psychiatric symptoms, and/or recurrent episodes of delirium, indicating that it is not necessarily synonymous with MCI-LB. Imaging, fluid and other biomarkers may play a crucial role in differentiating pDLB from pAD. The current MCI-LB criteria recognise low dopamine transporter uptake using positron emission tomography or single photon emission computed tomography (SPECT), loss of REM atonia on polysomnography, and sympathetic cardiac denervation using meta-iodobenzylguanidine SPECT as indicative biomarkers with slowing of dominant frequency on EEG among others as supportive biomarkers. This review also highlights the emergence of fluid and skin-based biomarkers. There is little research evidence for the treatment of pDLB, but pharmacological and non-pharmacological treatments for DLB may be discussed with patients. Non-pharmacological interventions such as diet, exercise, and cognitive stimulation may provide benefit, while evaluation and management of contributing factors like medications and sleep disturbances are vital. There is a need to expand research across diverse patient populations to address existing disparities in clinical trial participation. In conclusion, an early and accurate diagnosis of pDLB or pAD presents an opportunity for tailored interventions, improved healthcare outcomes, and enhanced quality of life for patients and care partners.

Keywords: Biomarkers; Clinical diagnosis; Early-stage dementia; Mild cognitive impairment; Neuropsychological profile; Psychiatric symptoms; Treatment planning.

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Conflict of interest statement

Carla Abdelnour is a member of the Board of Directors of the Lewy Body Dementia Association. Daniel Ferreira consults for BioArctic and has received honoraria from Esteve. Jon B Toledo is the Ann and Billy Harrison Centennial Chair in Alzheimer’s Research, Stanley H. Appel Department of Neurology and has consulted for GE Healthcare. Kathryn Wyman-Chick is funded by NIH (R21AG074368). Parichita Choudhury is funded by the Arizona Alzheimer’s Consortium and the Lewy Body Dementia Association. Ece Bayram is funded by NIH (K99AG073453) and the Lewy Body Dementia Association. Carla Abdelnour has received the Sue Berghoff LBD Research Fellowship, and honoraria as speaker from F. Hoffmann-La Roche Ltd, Zambon, Nutricia, Schwabe Farma Ibérica S.A.U. Elie Matar is funded by the National Health and Medical Research Council and US Department of Defense. He has received honoraria from the International Movement Disorders Society and CSL Seqirus. Paul Doneghy is funded by Medical Research Council (grant number MR/W000229/1) and the NIHR Newcastle Biomedical Research Centre. Federico Rodriguez-Porcel is funded by NIH (R21DC019749). Shannon Chiu is funded by NIH (K23AG073525). Matthew Barrett is funded by NIH (R21AG077469). Bhavna Patel is funded by NIH (K23AG073575) and Manugiran University of Florida Foundation Grant. Gregory Scott is funded by: VA Award IK2 BX005760-01A1 to GS, John and Tami Marick Family Foundation, Collins Medical Trust Award, Oregon Health & Science University Medical Research Foundation New Investigator Award, Oregon Alzheimer’s Disease Research Center, and Oregon Parkinson’s Center Research Pilot Award. Daniel Ferreira receives funding from the Swedish Research Council (Vetenskapsrådet, grant 2022-00916), the Center for Innovative Medicine (CIMED, grants 20200505 and FoUI-988826), the regional agreement on medical training and clinical research of Stockholm Region (ALF Medicine, grants FoUI-962240 and FoUI-987534), the Swedish Brain Foundation (Hjärnfonden FO2023-0261, FO2022-0175, FO2021-0131), the Swedish Alzheimer Foundation (Alzheimerfonden AF-968032, AF-980580, AF-994058), the Swedish Dementia Foundation (Demensfonden), the Gamla Tjänarinnor Foundation, the Gun och Bertil Stohnes Foundation, Funding for Research from Karolinska Institutet, Neurofonden, and the Foundation for Geriatric Diseases at Karolinska Institutet, as well as contributions from private bequests. Annegret Habich receives funding from the Swedish Dementia Foundation (Demensfonden), the Gamla Tjänarinnor Foundation, the Gun och Bertil Stohnes Foundation, and Funding for Research from Karolinska Institutet.

Figures

**Fig. 1**
A comparison of diagnostic criteria for and mild cognitive impairment with Lewy bodies (MCI-LB) and mild cognitive impairment due to Alzheimer’s disease (MCI-AD). The three essential criteria for MCI-LB [7] are broadly analogous to the NIA-AA definition of MCI-AD [44]. Aβ amyloid beta peptide, *CSF* cerebrospinal fluid, CT computed tomography, MR magnetic resonance imaging, *PET* positron emission tomography, *SPECT* single photon emission computed tomography

**Fig. 2**
Probable and possible mild cognitive impairment with Lewy bodies (MCI-LB). In addition to the presence of all three essential criteria (blue), two core features (pink), or one core feature and one positive proposed biomarker (purple), are required for a diagnosis of MCI-LB. The presence of either a positive biomarker or core feature in addition to all three essential criteria is suggestive of possible MCI-LB [7]

**Fig. 3**
Prodromal features of dementia with Lewy bodies. *DLB* dementia with Lewy bodies, *MCI-LB* mild cognitive impairment with Lewy bodies, *RBD* REM sleep behaviour disorder. Notably, prodromal DLB (pDLB) can present with cognitive impairment, psychiatric symptoms, and/or recurrent episodes of delirium. Therefore, pDLB is an umbrella term which includes, but is not limited to, presentations with mild cognitive impairment

See this image and copyright information in PMC

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Differentiating Prodromal Dementia with Lewy Bodies from Prodromal Alzheimer's Disease: A Pragmatic Review for Clinicians

Affiliations

Differentiating Prodromal Dementia with Lewy Bodies from Prodromal Alzheimer's Disease: A Pragmatic Review for Clinicians

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

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