Persistent dizziness or lightheadedness ranks among the most frequent complaints in primary care. Persistent dizziness is frequently described as a consequence or side effect of defined entities such as cardiovascular, infectious, neurological, and otological disease. Persistent dizziness is potentially disabling and has a distinct impact on participation, psychosocial interaction, and quality of life. We examined the relationship between persistent dizziness or lightheadedness and Alzheimer's disease (AD) markers among 924 individuals aged ≥50 years (52.3% male, mean age 74 years) selected from 5707 individuals who participated in the population-based Mayo Clinic Study of Aging in Olmsted County, Minnesota. Neuropsychiatric symptoms (depression and anxiety), cognitive evaluation (overall and across multiple domains), magnetic resonance imaging for AD-signature "regional thickness," and 11Carbon-Pittsburgh compound B positron emission tomography (11C-PiB PET) for Amyloid deposition are all investigated. Significant contributing factors to persistent dizziness in older adults were found and include [age, sex (male), lower education, high comorbidity index, high-density lipoprotein, balance problems, neuropsychiatric symptoms, cognitive impairments, and AD-signature” regional thickness]. After adjusting for age, sex, education, medical comorbidities, and other variables, a statistically significant association between persistent dizziness/lightheadedness and neuropsychiatric symptoms, and Amyloid-β deposition. This finding implies that the underlying AD biology may drive both the neuropsychiatric symptoms and persistent dizziness or lightheadedness, even before the onset of cognitive impairments and dementia. Further studies are needed to support the findings.