Cited by 152Dementia and Cognitive Impairment ResearchNeurological Disease Mechanisms and TreatmentsAlzheimer's disease research and treatments

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Mixed dementia: A review of the evidence

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Custodio, Nilton, Montesinos, Rosa, Lira, David, Herrera-Pérez, Eder, Bardales, Yadira, Valeriano-Lorenzo, Lucía·2017·Dementia & Neuropsychologia

DOI 10.1590/1980-57642016dn11-040005PMC PMC5769994

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Abstract

ABSTRACT. Mixed dementia is the coexistence of Alzheimer's disease and cerebrovascular disease (CVD) in the same demented patient. Currently, its diagnosis and treatment remains a challenge for practitioners. To provide an overview of the epidemiology, pathogenesis, natural history, diagnosis, and therapy of Mixed Vascular-Alzheimer Dementia (MVAD). The literature was reviewed for articles published between 1990-2016 by using the keywords linked to MVAD. Neuropathological studies indicate that MVAD is a very common pathological finding in the elderly with a prevalence about of 22%. The distinction between Alzheimer's dementia and vascular dementia (VD) is complex because their clinical presentation can overlap. There are international criteria for the MVAD diagnosis. The pharmacologic therapy shows modest clinical benefits that are similar among all drugs used in patients with Alzheimer's dementia and VD. The non-pharmacologic therapy includes the rigorous management of cardiovascular risk factors (especially hypertension) and the promotion of a healthy diet. The diagnosis and treatment of MVAD cannot be improved without further studies. Currently available medications provide only modest clinical benefits once a patient has developed MVAD. In subjects at risk, the antihypertensive therapy and healthy diet should be recommend for preventing or slowing the progression of MVAD.

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de Havenon, A., Gottesman, R. F., Willamson, J. D., Rost, N. S., Sharma, R., Li, V., Littig, L., Stulberg, E. L., Falcone, G. J., Prabhakaran, S., et al. (2024) · Alzheimer s & Dementia · doi:10.1002/alz.14126 · Cited by 11
“8 The least invasive measurement of AD amyloid beta (A β ) pathology is plasma biomarkers.”
Background
Pimavanserin for the treatment of psychosis in Alzheimer’s disease: A literature review
Srinivasan, S., Tampi, R. R., Balaram, K., & Kapoor, A. (2020) · World Journal of Psychiatry · doi:10.5498/wjp.v10.i7.162 · Cited by 11
Disrupted Structural White Matter Network in Alzheimer’s Disease Continuum, Vascular Dementia, and Mixed Dementia: A Diffusion Tensor Imaging Study
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Survival, cognitive functions, and brain MRI in patients with cSVD: 5-year observation
Добрынина, Л. А., Gadzhieva, Z. S., Kremneva, E. I., Витальевна, Ш. К., Tsypushtanova, M. M., Геннадьевна, М. А., Trubitsyna, V. V., Bitsieva, E. T., Filatov, A. S., Byrochkina, A. A., et al. (2022) · Annals of Clinical and Experimental Neurology · doi:10.54101/acen.2022.4.3 · Cited by 12
Beneath the Top of the Iceberg: Financial Capacity Deficits in Mixed Dementia with and without Depression
Giannouli, V., & Tsolaki, M. (2023) · Healthcare · doi:10.3390/healthcare11040505 · Cited by 10
“Mixed/multifactorial dementia (MD) is a condition in which a person has more than one type of dementia, and for the present study, it is defined as the combination of the two most prevalent types of dementia (most frequent in the older population), namely Alzheimer’s Disease (AD) and Vascular Dementia (VaD) and seems…”
BackgroundResultInfluential
Differences in pharmacologic and demographic factors in male and female patients with vascular dementia, Alzheimer's disease, and mixed vascular dementia
Stanley, M. C., Poupore, N. S., Knisely, K., Miller, A., Imeh‐Nathaniel, A., Roley, L. T., Nathaniel, S. I., Goodwin, R. L., & Nathaniel, T. I. (2023) · Frontiers in Dementia · doi:10.3389/frdem.2023.1137856 · Cited by 9
“This poses a challenge in the diagnosis and treatment of MVAD to clinicians, and most diagnostic procedures are biased toward AD (Custodio et al., 2017).”
Background
Thyroid Dysfunction, Vitamin B12, and Folic Acid Deficiencies Are Not Associated With Cognitive Impairment in Older Adults in Lima, Peru
Diaz, M. M., Custodio, N., Montesinos, R., Lira, D., Herrera‐Pérez, E., Pintado‐Caipa, M., Cuenca, J., Gamboa, C., & Lanata, S. (2021) · Frontiers in Public Health · doi:10.3389/fpubh.2021.676518 · Cited by 9
“of vascular cognitive impairment (39)]; (2) frontotemporal dementia (40); (3) mixed dementia [requires the existence of a typical AD and dementia related to cerebrovascular disease, as previously described (41, 42)]; (4) Dementia with Lewy bodies (43); or (5) AD (utilizing criteria published by McKhann et al.”
MethodSelf-citation
Neuropathological findings in Down syndrome, Alzheimer’s disease and control patients with and without SARS-COV-2: preliminary findings
Granholm, A., Englund, E. M., Gilmore, A., Head, E., Yong, W. H., Perez, S. E., Guzman, S. J., Hamlett, E. D., & Mufson, E. J. (2024) · Acta Neuropathologica · doi:10.1007/s00401-024-02743-9 · Cited by 11
“For cases obtained from Lund University (AD + COVID and Control + COVID), the diagnosis of AD and of vascular pathology, as well as the exclusion of such pathology in the controls and other pathology, was established in adherence with internationally accepted criteria for AD [15, 40, 60, 76].”
Method
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Pires, E. N. S., Ferreira, S. T., & Linden, R. (2020) · Journal of Neurochemistry · doi:10.1111/jnc.15129 · Cited by 9
“Such findings point to a scenario of mixed dementia, of which the prevalence, diagnosis, and treatment remain a challenge for physicians in general (Claus et al., 2016; Custodio et al., 2017; Rahimi & Kovacs, 2014).”
Background
An unbiased algorithm for objective separation of Alzheimer’s, Alzheimer’s mixed with cerebrovascular symptomology, and healthy controls from one another using electrovestibulography (EVestG)
Dastgheib, Z. A., Lithgow, B., & Moussavi, Z. (2022) · Medical & Biological Engineering & Computing · doi:10.1007/s11517-022-02507-1 · Cited by 9
“Criteria for the clinical diagnosis of AD-CVD are variable, whereas the existing diagnostic criteria for AD and VaD are of limited value for the diagnosis of AD-CVD [14].”
Background
Exploring the influence of weather variability and climate change on health outcomes in people living with dementia: A scoping review protocol
Lima, C. A., Alsunaidi, S., Lowe, S. A. J., Hogan, D. B., Dennett, L., Jones, C. A., & Yamamoto, S. S. (2024) · PLoS ONE · doi:10.1371/journal.pone.0304181 · Cited by 7
White matter hyperintensity severity modifies gut metabolite association with cognitive outcomes
Kijpaisalratana, N., Phuah, C., Ament, Z., Bhave, V. M., Guarniz, A. G., Duskin, J. A., Couch, C. A., Irvin, M. R., & Kimberly, W. T. (2025) · The Journal of Prevention of Alzheimer s Disease · doi:10.1016/j.tjpad.2025.100086 · Cited by 7
“The distinction between Alzheimer’s disease and VCID is challenging clinically [18–20].”
The role of arterial, venous blood and cerebrospinal fluid flow disturbances in forming cognitive impairment types in age-related cerebral microangiophathy
Добрынина, Л. А., Gadzhieva, Z. S., Akhmetzyanov, B. M., Kalashnikova, L. A., & Кротенкова, М. В. (2019) · S S Korsakov Journal of Neurology and Psychiatry · doi:10.17116/jnevro201911912281 · Cited by 7
Olfactory Bulb Proteomics Reveals Widespread Proteostatic Disturbances in Mixed Dementia and Guides for Potential Serum Biomarkers to Discriminate Alzheimer Disease and Mixed Dementia Phenotypes
Lachén‐Montes, M., Íñigo-Marco, I., Cartas‐Cejudo, P., Fernández‐Irigoyen, J., & Santamaría, E. (2021) · Journal of Personalized Medicine · doi:10.3390/jpm11060503 · Cited by 6
“dences of both AD and vascular disease [2].”
Background
Integrative machine learning approach to risk prediction for dementia and Alzheimer’s disease
Stern, A., & Linial, M. (2025) · GeroScience · doi:10.1007/s11357-025-01828-x · Cited by 5
“Mixed dementias, such as AD coexisting with vascular dementia (VaD), become more prevalent with age [23], with cerebral amyloid angiopathy (CAA) as a major contributor to vascular-related pathology [24].”
Associations of plasma biomarkers with longitudinal co-pathologies in Alzheimer’s disease and cerebral small vessel disease comorbidity
Yang, J., Zhao, X., Liu, Y., Cai, Y., & Fan, Y. (2026) · The Journal of Prevention of Alzheimer s Disease · doi:10.1016/j.tjpad.2025.100449 · Cited by 6
“Alzheimer ’ s disease (AD) and cerebral small vessel disease (CSVD) serve as the principal contributors to dementia in elderly individuals, [3,4] and frequently coexist clinically [5,6].”
Survival analysis of older adults with dementia: predicting factors after unplanned hospitalization in Maharaj Nakorn Chiang Mai Hospital
Yotruangsri, T., Phinyo, P., Buawangpong, N., Nantsupawat, N., Angkurawaranon, C., & Pinyopornpanish, K. (2024) · BMC Geriatrics · doi:10.1186/s12877-023-04558-x · Cited by 7
“Management and treat-ment of mixed dementia pose significant challenges, and existing regimens of medication provide modest clinical benefits [21, 22].”
Background
Increased risk of dementia in patients with primary Sjogren’s syndrome: a nationwide population-based cohort study
Lee, K., Jeon, H., Kim, H.-S., Choi, K., & Seo, G. H. (2025) · The Korean Journal of Internal Medicine · doi:10.3904/kjim.2023.536 · Cited by 5
Uncovering hidden subtypes in dementia: An unsupervised machine learning approach to dementia diagnosis and personalization of care
Campagner, A., Marconi, L., Bianchi, E., Arosio, B., Rossi, P., Annoni, G., Lucchi, T. A., Montano, N., & Cabitza, F. (2025) · Journal of Biomedical Informatics · doi:10.1016/j.jbi.2025.104799 · Cited by 5
Comorbidities and comorbidity burden in patients with neurocognitive disorders: findings from the MEMORA Cohort Study
Temedda, M. N., Garnier‐Crussard, A., Moutet, C., Mouchoux, C., & Dauphinot, V. (2025) · European Geriatric Medicine · doi:10.1007/s41999-025-01288-8 · Cited by 5
“According to the vascular theory, hypertension, peripheral vascular diseases and diabetes may contribute to neurovascular dysfunction in patients with AD [42], which may lead to MD.”
Gray and White Matter Voxel-Based Morphometry of Alzheimer’s Disease With and Without Significant Cerebrovascular Pathologies
Saha, C., Figley, C. R., Dastgheib, Z. A., Lithgow, B., & Moussavi, Z. (2024) · Neuroscience Insights · doi:10.1177/26331055231225657 · Cited by 5
“The cerebellar lobules (6, 7b, 8) that showed the GM difference in this study are from the cerebellum’s posterior lobules, engaged in cognitive and sensorimotor tasks.”
Background
Associations among Braak stage, Parkinsonian gait, cognition, and functional status in autopsy‐confirmed dementia with Lewy bodies
Mayo, A. M., & Peavy, G. M. (2019) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.5080 · Cited by 5
“Most recently, neuropathological evidence obtained at autopsy is demonstrating multiple coexisting pathologies.(3) However, research to understand the clinical presentation, level, and progression of functional impairment in the context of any”
Background
Emerging nano-derived therapy for the treatment of dementia: a comprehensive review
Ahmad, S., Ahmad, L., Adil, M., Sharma, R., khan, S., Hasan, N., & Aqil, M. (2025) · Drug Delivery and Translational Research · doi:10.1007/s13346-025-01863-3 · Cited by 4
Early Detection of Dementia Using a Large Language Model-Powered Chatbot
Routray, S., Samir, D., Pushya, G., & Srivastava, J. (2024) · International Conference on Parallel, Distributed and Grid Computing (PDGC) · doi:10.1109/pdgc64653.2024.10984295 · Cited by 4
“The most common combination is AD and VaD dementia, which is mainly related to old age, high blood pressure, and damaged blood vessels of the brain [11,27].”
Ginkgo biloba for cognitive impairment and dementia
Wieland, L. S., Ludeman, E. M., Chi, Y., Feinberg, T., Chen, I., Chen, K., Zhu, Y., Wolverson, E., & Amri, H. (2026) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd013661.pub2 · Cited by 4
Baseline Profiles of Drug Prescriptions Prior to Diagnosis of Mild Cognitive Impairment (MCI) Obtained by Latent Class Analysis (LCA), and Assessment of Their Association with Conversion to Dementia
Gómez-Gómez, C., Moya-Molina, M. Á., Tey-Aguilera, M. J., Flores-Azofra, J., & González-Caballero, J. L. (2023) · Healthcare · doi:10.3390/healthcare11152219 · Cited by 5
Assessing adherence to National Institute for Health and Care Excellence dementia assessment and diagnosis guidelines in adults with intellectual disability: a retrospective cohort study
Duncan, C., Wilkinson, E., Jaydeokar, S., & Acton, D. (2023) · Advances in Mental Health and Intellectual Disabilities · doi:10.1108/amhid-07-2023-0022 · Cited by 4
Evaluating the Diagnostic Value of Electrovestibulography (EVestG) in Alzheimer’s Patients with Mixed Pathology: A Pilot Study
Dastgheib, Z. A., Lithgow, B., & Moussavi, Z. (2023) · Medicina · doi:10.3390/medicina59122091 · Cited by 4
“While there are accepted criteria to diagnose AD and VaD [2,6,15], there is little consensus for the diagnosis of AD-CVD (mixed pathology) [16].”
Background
How Do Spouses Experience Living Alone After Their Partner With Dementia Moves Into a Care Home?
Pope, B., Gelling, L., Holland, S., & Cox, C. (2025) · Journal of Clinical Nursing · doi:10.1111/jocn.17831 · Cited by 4
Liver Fibrosis and the Risks of Impaired Cognition and Dementia: Mechanisms, Evidence, and Clinical Implications
Jamalinia, M., Weiskirchen, R., & Lonardo, A. (2026) · Medical Science · doi:10.3390/medsci14010044 · Cited by 3
“Several other subtypes of dementia, including dementia with Lewy bodies [41], frontotemporal dementia [42], and mixed dementias, are particularly common in older individuals in whom processes of neurodegeneration and vascular pathology often coexist [43].”
MRS demonstrates elevated brain glutathione in vascular mild cognitive impairment compared to cognitively normal coronary artery disease controls
Chen, J. J., Kang, Y., Gallagher, D., Herrmann, N., Survilla, K., Vieira, D., Mah, E., Graham, S. J., Kiss, A., Black, S. E., et al. (2025) · Alzheimer s & Dementia · doi:10.1002/alz.70230 · Cited by 3
“68 Another strength of the present study is that vMCI participants underwent amyloid PET imaging.”
Five-Word Test, Screening of Mixed Dementia in Older Adults. Validation Study
Mimenza-Alvarado, A. J., Bombón-Albán, P. E., Duarte-Flores, J. O., Gutiérrez-Gutiérrez, L., Ávila‐Funes, J. A., & Aguilar-Navarro, S. G. (2021) · Revista Colombiana de Psiquiatría · doi:10.1016/j.rcp.2021.04.009 · Cited by 3
Nonpharmacological intervention therapies for dementia: potential break-even intervention price and savings for selected risk factors in the European healthcare system
Marešová, P., Rezny, L., Bauer, P., Valko, M., & Kuča, K. (2024) · BMC Public Health · doi:10.1186/s12889-024-18773-7 · Cited by 3
“Custodio et al. reported a 22% share of MD (AD with VaD) among patients with dementia [52].”
Background
Clinical practice guidelines on addressing cognitive impairment in vascular dementias
Singh, S. M., Kathiresan, P., & Gaur, N. (2025) · Indian Journal of Psychiatry · doi:10.4103/indianjpsychiatry.indianjpsychiatry_713_24 · Cited by 2
Alzheimer’s Disease–Thrombosis Comorbidity: A Growing Body of Evidence from Patients and Animal Models
Koch‐Paszkowski, J., Sennett, C., & Pula, G. (2025) · Cells · doi:10.3390/cells14141069 · Cited by 5
“…the number of patients showing both amyloid plaque deposition (i.e., the hallmark of AD) and neurovascular impairment has increased significantly [14], with mixed vascular-Alzheimer dementia (MVAD) becoming the most common forms of mixed dementia (22% of all current dementia diagnoses) [15].”
Automated Advancements and Synergistic Challenges in Multi-Modal Clinical Assessments for Alzheimer’s Disease Diagnosis: A Comprehensive Review and Meta-Analysis
Rajput, M. D., Bawa, P., Kadyan, V., & Sethi, M. (2025) · Archives of Computational Methods in Engineering · doi:10.1007/s11831-025-10427-0 · Cited by 2
Interrelationships of social determinants with cognition, vascular health, and physical functioning
Amofa, P., Fiala, J. A., Levy, S.-A. T., Ross, K. M., Walker, A. F., & Smith, G. E. (2025) · Alzheimer s & Dementia Behavior & Socioeconomics of Aging · doi:10.1002/bsa3.70013 · Cited by 2
Brain morphological characteristics predicting clinical response to selective serotonin reuptake inhibitors or cholinesterase inhibitors: A study of electronic medical records in patients with cognitive disorders
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Cerebral toxoplasmosis and alcohol abuse in AIDS: dementia with multiple etiologies
de Almondes, K. M., & Lima, N. C. (2020) · Dementia & Neuropsychologia · doi:10.1590/1980-57642020dn14-040014 · Cited by 3
Older Veterans
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Liposome: A potential drug delivery vector to treat dementia
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Tremor in Vascular Cognitive Impairment Raises the Possibility of Mixed Pathology With Lewy Body Disease
Chiu, P., Tzeng, R.-C., Wei, C.-Y., Hung, G., & Hu, C. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00781 · Cited by 1
“Mixed dementia have traditionally focused on the coexistence of Alzheimer’s disease (AD) and CVD in the same demented patient (Langa et al., 2004; Custodio et al., 2017).”
Background
Solid lipid nanoparticles-based drug delivery for dementia
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The diagnostic accuracy of CTseg segmentation software for dementia in a New Zealand memory service
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“12 For a diagnostic test to be useful, it must be applicable in a real-world clinical setting (for example, in an AI-assisted diagnostic system) and be able to distinguish patients with true dementia from those with without dementia within a full spectrum of brain pathology, while also minimizing…”
EPIDEMIOLOGY OF ALZHEIMER'S DISEASE AND DEMENTIA IN INDIA: A SYSTEMATIC LITERATURE REVIEW
Zafar, M. N. (2025) · Medical Science of Ukraine (MSU) · doi:10.32345/2664-4738.2.2025.14 · Cited by 1
“Diagnosis of vitamin B 12 insufficiency can be made by measuring serum vitamin B 12 levels, along with tests for serum homocysteine levels and complete blood counts [23,24].”
Interactive Effects of Plasma Alzheimer Disease Biomarkers and White Matter Hyperintensities on Cognitive Decline and Clinical Progression in Nondemented Adults
Yang, J., Zhao, X., Liu, Y., Cai, Y., Fan, Y., & Initiative, A. T. A. D. N. (2026) · Journal of the American Heart Association · doi:10.1161/jaha.126.050676 · Cited by 1
Hypertension and Diabetes Mellitus are Features of Vascular Dementia, Not Alzheimer?s Disease
Javanshiri, K., Haglund, M., & Englund, E. M. (2019) · Journal of Neurology & Neurophysiology · doi:10.4172/2155-9562.1000482 · Cited by 1

Authors: Custodio, N., Montesinos, R., Lira, D., Herrera-Pérez, E., Bardales, Y., & Valeriano-Lorenzo, L.
Affiliations: Instituto Peruano de Neurociencias (PE)
Instituto Peruano de Neurociencias, Perú; Instituto Nacional de Salud del Niño, Perú; GESID, Peru
Corresponding author: Custodio, Nilton
ORCID: Custodio, Nilton
Montesinos, Rosa
Lira, David
Venue: Dementia & Neuropsychologia
Publisher: FapUNIFESP (SciELO)
Published: 2017-12
Volume: 11
Issue: 4
Pages: 364-370
ISSN: 1980-5764 (ISSN-L)
DOI: 10.1590/1980-57642016dn11-040005
PMC: PMC5769994
OpenAlex: W2784098514
Cited by: 148
References: 77
Citations by year: 2026: 16 · 2025: 26 · 2024: 15 · 2023: 27 · 2022: 17 · 2021: 14 · 2020: 13 · 2019: 13 · 2018: 7
FWCI: 7.42
Type: journal article
Language: en
Open access: diamond
doi.org
Licence: cc-by
Locations: Dementia & Neuropsychologia (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (publishedVersion, other-oa)
Americanae (AECID Library) (submittedVersion, cc-by-nc)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Redalyc (Universidad Autónoma del Estado de México) (submittedVersion)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Keywords: Alzheimer's disease, cerebrovascular disease, vascular dementia, dementia diagnosis, dementia pathogenesis, dementia epidemiology, natural history of dementia, pharmacotherapy, non-pharmacological treatment, cardiovascular risk factors, hypertension, healthy eating, dementia prevention

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Mixed dementia: A review of the evidence

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