Companion dogs: sentinels for multimorbidity of human neurocognitive-sensory aging and susceptibility to Alzheimer’s disease and related dementias

The co-occurrence of age-related cognitive and sensory organ impairments exacerbates negative effects on the health, lifestyle, and quality of life of older adults. These age-related multimorbidities include Alzheimer’s disease and Alzheimer’s disease related dementias (AD/ADRD), in addition to sensory declines such as loss of vision, hearing, and olfaction (sense of smell). We hypothesize that these multimorbidities share common neurotoxicant risk factors that are present in the home environment. With the recent increase in time spent at home, the human exposure to home environment neurotoxicants is changing. However, the effects of these changes on the risk of developing neurocognitive-sensory aging and AD/ADRD are unknown and will take many decades to understand in humans. We propose to study pet (companion) dogs as an efficient sentinel model for the human health impacts of home environment-derived neurotoxicants. Pet dogs are promising sentinels as they share the human indoor and outdoor home environment, share similar exposure to toxicants in the home, yet have shorter latency of onset of toxic effects. Dog lifespan is significantly shorter than humans, yet both species experience similar multimorbidities of neurocognitive-sensory aging. Therefore, epidemiologic studies in dogs could help us quickly understand the human health implications of changes in risk factor exposure. We will determine shared human/dog neurotoxicant exposure and dog neurocognitive-sensory outcomes related to a common group of neurotoxicants found in the home environment, the toxic heavy metals As, Cd, Cr, Hg and Pb. These metals accumulate in neurologic tissues and have well-defined neurotoxic effects, but their effect on age-related neurologic decline is unclear. In Aim 1 we will establish shared risk of multimorbidity of neurocognitive-sensory aging in cohabiting humans and dogs. We will determine the cognitive and sensory function declines associated with aging in dogs and relate the trajectory of dog declines to cohabiting human declines. In Aim 2 we will validate companion dogs as sentinels for human and environmental heavy metal exposure by comparing drinking water and house dust concentrations of heavy metals with dog and human blood concentrations of heavy metals. In Aim 3 we will determine the impact of high heavy metal burden on dog neurocognitive-sensory aging multimorbidities, and on metabolism in the blood. The outcomes of this work will establish the companion dog as a relevant, expedient surrogate model of human age-related neurocognitive-sensory decline and AD/ADRD risk and confirm that humans and dogs share home environment heavy metal risk factors that increase the risk of metabolic dysfunction and neurocognitive-sensory decline in aging. Future studies could utilize this sentinel dog model to test promising therapeutics prior to translation to humans. This work is relevant to the mission of multiple NIH institutes as it encompasses the important topics of aging, cognitive decline, sensory decline, and toxicant risk factors for neurocognitive-sensory aging and AD/ADRD risk in a relevant animal model with an accelerated timeline.