First Advisor

Randall Woltjer

Date of Award


Document Type


Degree Name

Bachelor of Science (B.S.) in Biology and University Honors




Brain -- Degeneration, Dementia, Alzheimer's disease, Mild cognitive impairment




Dementia is cognitive impairment often associated with old age diseases namely, Alzheimer's Disease. However, contrary to popular beliefs, dementia is divided into multiple subgroups according to age and disease progression. Interestingly, patients in the older subgroups often do not display characteristic pathologies, such as beta-amyloid plaques and neurofibrillary tangles, in high abundance as observed in patients with Alzheimer's Disease. Instead, cerebrovascular disease in the form of large or many smaller strokes is more commonly present. A notable novel observation made in the older group has been nonviable but preserved "mummified" neurons which resemble those found in an inherited, childhood disease known as pantothenate kinase associated neurodegeneration (PKAN); hence the name "PKAN neurons" for these lesions. For this project, we focused on quantifying the presence of PKAN neurons, plaques, and tangles in patients with Alzheimer's Disease (AD), mild cognitive impairment (MCI), an older subgroup of cognitive impairment designated based on their clinical and demographic features as "Disease of the Oldest Old" (DOOO), and cognitively control subjects. The PKAN neuron density was calculated to be highest in patients with DOOO (86.39 ± 17.90 N=7) when compared to the age-matched control group (4.488 ± 1.274 N=6) with a p-value of 0.0015. We also noted the inverse relationship between PKAN neurons and plaques and tangles across all age-related dementia groups. Our results confirm a dichotomy of dementia in patients with clinical AD, with younger patients having a large burden of AD-associated lesions and older patients with a combination of AD lesions and inversely related PKAN neurons. The results introduce PKAN neurons recognized as a novel feature of dementia, which complement classic AD-associated lesions as correlates of cognitive impairment in more elderly patients.


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