Is Tau Protein Linked to Mobility Function?

Impaired mobility is strongly linked to cognitive function and vice versa. Cognitive
functions are strongly associated with mobility function, most commonly assessed using gait
speed. In the Health ABC Study, Digit Symbol Substitution Test (DSST) and Modified Mini
Mental Status (3MS) scores were significantly associated with gait speed and gait speed
decline. Poor lower extremity performance predicts faster age-related cognitive decline and
increased incidence of mild cognitive impairment (MCI) and dementia. This study will explore
the role of tau protein as the neuropathologic basis for these associations.

Brain imaging markers may be the link between cognitive measures and gait. White matter
disease is commonly measured by quantifying white matter (WM) lesion load, which is
associated with small vessel ischemic disease. More subtle microstructural changes can be
observed by calculating fractional anisotropy (FA) from diffusion tensor imaging (DTI). Aging
is accompanied by changes in cortical volume, white matter microstructure and an increased
prevalence of WM lesions. WM lesions have been strongly implicated in declining physical
function. These brain changes are associated with impaired balance, slower movement speeds,
slower chair stand times and increased falls risk.Recently, Aâ accumulation in the brain has
also been linked to slow gait. This finding suggests a pathologic mechanism linking Alzheimer
s disease processes to gait impairments. However, Aâ accumulation itself may not be the
critical neuropathic change. In recent studies of Aâ42 and phosphorylated tau protein in
cerebral spinal fluid, it has been found that low Aâ42 levels themselves are not associated
with impaired cognition, but that elevated tau levels are also required. If the process of
cognitive impairment parallels the process of gait impairment, it might be that tau levels
are more important correlates of gait changes. To the investigators' knowledge the
relationship between CSF tau levels and mobility has never been explored. PET ligands for
brain tau have recently become available, but the relationship between brain tau accumulation
and gait has yet to be determined. In this study, investigators will relate gait
characteristics to CSF Aâ42 and phosphorylated tau levels, and perform brain PET imaging in a
subset to related tau protein accumulation to gait characteristics for the first time. Both
mobility impairment and Alzheimers disease (AD) occur in the context of the aging vascular
system. Over the past 15 years, it has been recognized that abnormalities of thoracic aortic
stiffness are associated with the development of abnormalities in small vessels supplying the
brain and kidneys. As the aorta stiffens, the propagation speed of the systolic flow wave
increases through the aortic lumen. (Stiffness within the thoracic aorta can be accomplished
through measurement of aortic pulse wave velocity.) In hypertensive patients, aortic archway
pulse wave velocity has been associated with increases in left ventricular mass as well as
lacunar brain infarcts independent of age, sex, and the duration of hypertension. In the
Multi-Ethnic Dallas Heart Study aortic arch pulse wave velocity is an independent predictor
of white matter hyper-intensities. In those with diabetes, increasing aortic stiffness
contributes to the development of small vessel microvascular dysfunction which is associated
with deep white matter atrophy as well as cognitive decline. Recently, a stiffness mismatch
between the thoracic aorta and small vessels within the cerebral microcirculation has been
described. This mismatch impacts microvascular pulsatility and appears to diminish diffusion
anisotrophy between the cerebral spinal fluid and the CNS microcirculation. This observation
may contribute to retained amyloid type protein in those with AD.

Inclusion Criteria:

- 50+ years of age and participated in the Wake Forest Alzheimer's Disease Core Center
study

- Willing to provide informed consent

- Not dependent on a walker

Exclusion Criteria:

- Recent cardiac event in the last 6 months

- Uncontrolled hypertension (BP >200/110 mmHg)

- Neurological (e.g., Parkinson's) or hematological disease

- Participants with a knee replacement in last 6 months

- Participants with recent eye surgery in last 6 months

- Severe musculoskeletal impairment (e.g., sciatica, fibromyalgia, severe leg/back pain)

- If willing to get an MRI, must not have indwelling metal-contraining prosthesis,
pacemaker or defibrillator, history of welding, permanent make up or head/neck tattoo,
or any other contraindication to MRI