Research suggests that the symptoms indicative of these conditions – cognitive impairment in AD, motor impairments in PD, for example – are late developments that occur far downstream of neuronal energy deficits that begin decades before diagnosis. All four conditions addressed in the paper are associated with alterations in mitochondrial structure and function and decreased neuronal ATP synthesis, which are hypothesized to begin long before the signature pathological features become evident.
The paper identifies numerous factors as potential contributors to the cellular dysfunction in these conditions, such as toxic environmental exposures (e.g., heavy metals, air pollution, pesticides), poor sleep, social isolation, physical inactivity, and the modern diet, with its preponderance of refined carbohydrates and multiple daily feeding opportunities with little to no periods of fasting or digestive rest.
Existing treatments for neurodegenerative disorders are associated with unwanted side-effects and may lose efficacy over time. Moreover, they are primarily aimed at symptom suppression and do little to address the underlying root causes because it’s not known for certain what the root causes are. But this paper is a step forward toward this end and presents a well-reasoned overview of what could potentially be contributing to these refractory conditions, how and why they are much more alike than is commonly acknowledged, their numerous shared molecular signatures, and what types of interventions may be more effective than current treatments are for restoring healthy neuronal function.