Reader response: Olfaction and risk of dementia in a biracial cohort of older adults

We read with great interest the article by Yaffe et al.¹ in which a strong association between poorer olfaction and incident dementia was reported. Exposure to airborne lead pollution decades earlier may play a role in this association. In older adults, higher cumulative lifetime exposure to lead, a well-established neurotoxin, was associated with impaired memory and accelerated declines in cognition,^2–4 as well as smaller total brain volume, smaller volume of frontal and total gray matter, and more prevalent and serious white matter lesions.⁴ In primate studies, early life exposure to lead was associated with a greater burden of both β-amyloid plaques and neurofibrillary tangles in later life.^2,3 Among older humans, the primary exposure pathway for lead was through inhalation of airborne lead pollution from leaded gasoline; mean blood lead levels declined 78% between 1976 and 1991 with the phase out of leaded gasoline.² Cumulative lifetime lead exposure is associated with markedly worse olfactory function, and there is a negative dose–response relationship between exposure to vehicle exhaust and olfaction.⁵ A recent review suggested, “Inhaled Pb is likely able to directly reach olfactory tissues and translocate to the brain, given its strong deleterious neurocognitive effects.”⁵