Continuous non-invasive assessment of blood pressure profile in persons with Alzheimer's and its related dementias

Abstract: The current standard-of-care for measurement of BP monitoring is the periodic use of occlusive arm- cuff devices. However, its utility is compromised by two critical limitations to measuring an individual’s true BP: 1) overall measurement inaccuracy and 2) inability to measure BP continuously. These limitations underscore a critical unmet need for accurate, continuous, non-invasive blood pressure (cNIBP) monitoring that can be used for management of hypertension (HTN) and other chronic diseases. To address this need, we have developed ViTrack™, a cuffless, wrist-wearable device that uses a fundamentally new method to accurately and non- invasively measure BP continuously. ViTrack’s beat-to-beat continuous measurements accurately provides patient’s true BP, including daytime and nighttime BP, circadian BP patterns, and BP variability (BPV). ViTrack also measures heart rate, respiratory rate, and wrist actigraphy to assess activity/sleep patterns. In Direct-to- Phase-II study [Grant#:1R44 HL158374-01] we are assessing BP parameters in a wide range of patients. ViTrack will address the need for accurate and continuous BP monitoring to prevent disabilities in persons with Alzheimer’s disease and its related dementias: HTN is the most common co-morbidity in persons with Alzheimer’s disease and its related dementias [1]. Effective HTN therapy offers the chance to reducing disability from cardiovascular or cerebrovascular events [2]. However, optimal management of HTN in people with dementia is hampered by the current dependence on periodic blood BP monitoring using occlusive arm-cuff devices [2]. Persons with dementia often have sleep disturbances and behavioral issues, in addition to autonomic dysfunction, which can significantly affect BP hemodynamics. These are almost never detected by random solitary measurements in the clinical setting [3,4,5]. Adding another challenge, dementia patients with poorer cognitive ability and behavioral issues do not tolerate frequent BP measurements [6]. HTN drug treatment tailored to circadian BP profile is critical to avoid orthostatic hypotension and/or hypotension, which can lead to weakness, contribute to falls and further cognitive decline [7,8,9,10]. Furthermore, the co-occurrence of behavioral events and BP changes in people with dementia is well recognized and perhaps modifications in BP could prevent or temper their agitation or aggression [11]. Thus, the development of rational therapeutic strategies to modulate BP and reduce disability in those with Alzheimer’s disease and its related dementias is dependent upon accurately assessing and characterizing their BP profile. ViTrack enables nonintrusive gathering of a patient’s beat-to-beat 24-h BP profile, both accurately and reliably, for the first time. ViTrack can address the need for accurate, continuous, and ubiquitous BP measurements for Alzheimer’s disease and vascular cognitive impairment–dementia prevention: Almost 40% of the US adult population has HTN [12]. Evidence suggests that midlife HTN contributes significantly to the development and progression of both Alzheimer’s disease and vascular cognitive impairment–dementia [13,14,15,16,17,18]. The Systolic Blood Pressure Intervention Trial (SPRINT)-MIND, demonstrated that intensive BP control (SBP lt120) was associated with a significant reduction in the rate of minimal cognitive impairment and trended toward reducing the rate of dementia development compared to standard BP control (SBP 135-140) [19]. While SPRINT- MIND has reemphasized the broader public health benefits of BP lowering, confidence in the data is diminished by use of periodic clinic BP measurements [20]. These same impediments compromise population-level lifecourse interventions for BP control and dementia prevention [21,22,23,24]. Random cuff measurements lead to a 30% error rate in HTN diagnosis [25,26] and are not optimal for HTN management. Hence, lt 50% of patients with HTN are poorly controlled [27,28]. Increased BPV and nighttime BP abnormalities are independent risk factors for dementia [29,30,31,32,33,34]. Recent systematic review and meta-analysis shows the relative contribution of BPV to the risk of dementia and cognitive impairment exceeded that of mean BP [35]. But accurate assessments of BPV and nocturnal BP are among the most difficult to obtain using periodic, cuff-based BP methods [36]. ViTrack can provide accurate measure of 24-hr mean BP, nighttime BP profile and BPV to reliably evaluate risk and control BP to protect brain health and prevent or slow the progression of dementia in later age. In this Supplemental grant, we propose to expand our ongoing clinical study to collect beat-to-beat 24-hour BP with ViTrack in age-matched subjects with and without Alzheimer’s disease and its related dementias (N=25 per group; total = 50). The study is adequately powered to compare BP profile (24-h mean SBP and DBP; daytime and nighttime mean SBP and DBP; BPV) between the groups. This pilot data can be used to design more extensive longitudinal trials that will define the potential hemodynamic benefits of therapeutic interventions in these groups, as a strategy to prevent additional disabilities in persons with dementia. The proposed pilot study will also further validate ViTrack’s promise as an individual and population level tool, as part of a lifecourse strategy, to assess and control BP in order to protect brain health and mitigate the risk of age-related dementia.