Case Study: A Precision Medicine Approach to Multifactorial Dementia and Alzheimer's Disease

Abstract

We report a case of a patient with mixed dementia successfully treated with a personalized multimodal therapy. Monotherapeutics are inadequate for the treatment of Alzheimer's disease (AD) and mixed dementia; therefore, we approach treatment through an adaptive personalized multimodal program. Many multimodal programs are pre-determined, and thus may not address the underlying contributors to cognitive decline in each particular individual. The combination of a targeted, personalized, precision medicine approach using a multimodal program promises advantages over monotherapies and untargeted multimodal therapies for multifactorial dementia. In this case study, we describe successful treatment for a patient diagnosed with AD, using a multimodal, programmatic, precision medicine intervention encompassing therapies targeting multiple dementia diastheses. We describe specific interventions used in this case that are derived from a comprehensive protocol for AD precision medicine. After treatment, our patient demonstrated improvements in quantitative neuropsychological testing, volumetric neuroimaging, PET scans, and serum chemistries, accompanied by symptomatic improvement over a 3.5-year period. This case outcome supports the need for rigorous trials of comprehensive, targeted combination therapies to stabilize, restore, and prevent cognitive decline in individuals with potentially many underlying causes of such decline and dementia. Our multimodal therapy included personalized treatments to address each potential perturbation to neuroplasticity. In particular, neuroinflammation and metabolic subsystems influence cognitive function and hippocampal volume. In this patient with a primary biliary cholangitis (PBC) multimorbidity component, we introduced a personalized diet that helped reduce liver inflammation. Together, all these components of multimodal therapy showed a sustained functional and cognitive benefit. Multimodal therapies may have systemwide benefits on all dementias, particularly in the context of multimorbidity. Furthermore, these therapies provide generalized health benefits, as many of the factors - such as inflammation - that impact cognitive function also impact other systems.

Keywords: Alzheimer; dementia; dementia-multifactorial; lifestyle; multimodal; multimorbidity; neuroplasticity; primary biliary cholangitis.

Conflict of interest statement

Conflicts of Interest The authors have no conflicts of interest to declare.

Figures

Figure 1.

Trajectories of select clinical chemistries. Hippocampal volume measurements are shown for comparison. Orange line; upper bound of reference. Blue line; lower bound of reference. Multimodal treatment of the entire individual results in subtle changes that impact many physiological subsystems. Although these impacts often change trajectories only within traditional reference ranges, the cumulative effect on well being may be pronounced.

Figure 2.

Hippocampal volume changes in the patient from 2016 to 2019. The hippocampal volume decreased from 2016 to 2017 (red line) and then increased between 2017 and 2019 (green line). Volumes were determined with Neuroreader software.

Figure 3.

Organization and detail of Rey figure drawing from 2017 to 2019.