The Alzheimer’s Prevention Clinic at Weill Cornell Medical College / New York - Presbyterian Hospital: Risk Stratification and Personalized Early Intervention

Abstract

In July 2013, Weill Cornell Medical College founded the first Alzheimer’s Prevention Clinic (APC) in the United States, providing direct clinical care to family members of patients with Alzheimer’s disease (AD) as part of the Weill Cornell Memory Disorders Program. At the APC, patients seeking to lower their AD risk undergo a comprehensive assessment, receive a personalized plan based on rapidly evolving scientific evidence, and are followed over time using validated as well as emerging clinical and research technologies. The APC approach applies the principles of pharmacogenomics, nutrigenomics and clinical precision medicine, to tailor individualized therapies for patients. Longitudinal measures currently assessed in the clinic include anthropometrics, cognition, blood biomarkers (i.e., lipid, inflammatory, metabolic, nutritional) and genetics, as well as validated, self-reported measures that enable patients to track several aspects of health-related quality of life. Patients are educated on the fundamental concepts of AD prevention via an interactive online course hosted on Alzheimer’s Universe (www.AlzU.org), which also contains several activities including validated computer-based cognitive testing. The primary goal of the APC is to employ preventative measures that lower modifiable AD risk, possibly leading to a delay in onset of future symptoms. Our secondary goal is to establish a cohort of at-risk individuals who will be primed to participate in future AD prevention trials as disease-modifying agents emerge for testing at earlier stages of the AD process. The clinical services are intended to lower concern for future disease by giving patients a greater sense of control over their brain health.

Individualized clinical management of patients at risk for Alzheimer's dementia

“…An overall structure of how precision medicine may be achieved in the future will be through convergence of technological advances (e.g., big data, genomic sequencing, "-omics" technologies, systems biology, integrated disease modeling) as it is hypothe-sized that deconstructing the disease into multiple subsets that exist within a heterogeneous population, and tailoring therapies accordingly, may be preferentially effective based on individual biological make-up (protein-protein interactions, epigenetic modifications, metabolic pathways) [17,18]. A term that has been used to adapt this approach, using currently available clinical assessments in everyday practice [19], is clinical precision medicine, where medical history (e.g., lifestyle patterns, life-course events), physical/neurological examination, anthropometrics, commercially available blood biomarkers (including genetics), and cognitive assessments inform a multimodal management plan [20,21]. Patients are followed up longitudinally to evaluate the effectiveness of, and further refine, personally tailored interventions.…”

“…Patients are followed up longitudinally to evaluate the effectiveness of, and further refine, personally tailored interventions. In 2013, an Alzheimer's Prevention Clinic (APC) was established in New York, with research collaboration in Puerto Rico [21,22]. APC's mission is to mitigate late-life AD dementia risk by applying individualized clinical management strategies toward primary, secondary, and tertiary AD prevention while simultaneously studying its comparative effectiveness (Supplementary Fig.…”

Exosomes in Age-Related Cognitive Decline: Mechanistic Insights and Improving Outcomes

“…Indeed, the only FDA approved treatments for dementia (i.e., cholinesterase inhibitors, NMDA antagonist, Aβ antibodies) are specified for persons already exhibiting symptoms; however, the underlying neurobiology of cognitive decline is hypothesized to begin years or decades before the onset of behavioral impairments ( Long and Holtzman, 2019 ). Therefore, using exosomes as biomarkers to enhance detection of susceptible individuals may facilitate intervention by health care providers (e.g., enrolling in clinical trials, implementing risk-reduction strategies) and ultimately improve prognosis ( Ngandu et al, 2015 ; Seifan and Isaacson, 2015 ).…”

Dementia Prevention in Clinical Practice

“…Often, family history of AD or dementia is the primary motivator for patients to seek risk reduction management. 20 21 As AD is responsible for 60 to 80% of all dementia cases, and significant overlap between clinical presentation exists, other less common forms of dementia are often misdiagnosed as AD. 22 23 24 It is necessary to diligently investigate any family history of diagnosed AD, other dementias, or undiagnosed symptoms of cognitive impairment—especially in first-degree relatives—along with the age of onset and clinical presentation for any affected relatives.…”

“…Obtaining advanced lipid panels to better guide risk stratification and to monitor adequacy of lipid lowering therapy has been successfully deployed in AD prevention clinical practice over the last decade. 20 21 30 31 In apolipoprotein E (ApoE4) carriers, Apo-A1 (a component of HDL cholesterol) is a marker for increased AD risk, whereas N-terminal probrain natriuretic peptide (NT-proBNP) is a plasma protein associated with VaD. 32 33 Insulin resistance is associated with poor cognitive function and can promote neuroinflammation and amyloid deposition.…”