Brain Alterations and Cognitive Impairment in Older Adults With Heart Failure

Cognitive impairment, commonly reported as difficulty with memory and executive function, is
a widely recognized clinical challenge for persons > 65 years old with HF. Although the
degree of cognitive impairment usually does not meet the criteria for dementia, it can affect
an individual's ability to process and remember information, such as complex medication
regimens [5]. Findings suggest that brain regions that support memory (i.e. temporal lobe)
and executive function (i.e. prefrontal cortex) may be altered in older persons with HF;
suggesting that these brain alterations are related to the HF disease process and not normal
aging. Surprisingly, despite the high prevalence of cognitive impairment in HF, relationships
between brain and cognition have not been well studied.

Little is known about the relationships between brain magnetic resonance imaging (MRI) and
cognitive impairment in older persons with HF. A limited number of studies have investigated
brain MRI in adults with HF and produced conflicting results. Three studies utilized
structural MRI techniques and identified evidence of atrophy in the temporal lobe,
hippocampus, and prefrontal cortex and an increased volume of white matter hyperintensities
[6-8]. Brain hypoperfusion, operationalized as decreased global cerebral perfusion, was
identified in two studies [9, 10]. Only one study examined relationships between brain MRI
and cognitive impairment in HF [6]. Vogels et al., (2007) found that atrophy in the medial
temporal lobe was associated with decreased measures of memory and executive function. White
matter hyperintensities did not correlate with any cognitive measures. Limited research
findings indicate that various brain alterations in the temporal lobe, hippocampus, and
prefrontal cortex contribute to cognitive impairment in HF. However, previous findings are
limited by use of lower resolution scanners (1.5 Tesla), lack of MRI techniques (i.e.
structural and perfusion scans) and recruitment of mixed age samples.

Based on these limitations, the purpose of this research plan is to explore relationships
between brain MRI and cognitive impairment in older persons with HF using high resolution
structural and perfusion scans. To accomplish this goal, investigators will compare 40 adults
with HF who are > 65 years old with 40 healthy, gender, age, and education matched controls.
Investigators will obtain neuropsychological measures of multiple domains, as well as MRI
measurements of the temporal lobe and prefrontal cortex at baseline and 12-months. The
following specific aims will be investigated:

Aim 1: Compare brain MRI in older persons with HF and controls at baseline and 12-months.

Hypothesis 1a: Older persons with HF will have increased white matter hyperintensities,
decreased grey matter volume, and decreased perfusion in the temporal lobe and prefrontal
cortex compared with controls. Hypothesis 1b: Older persons with HF will exhibit a greater
decline in grey matter volume in the temporal lobe and prefrontal cortex over 12-months
compared with controls.

Aim 2: Compare cognitive function in older persons with HF and controls at baseline and
12-months.

Hypothesis 2a): Older persons with HF will perform lower on measures of memory and executive
function compared with controls.

Hypothesis 2b): Older persons with HF will exhibit a greater decline on measures of memory
and executive function over 12-months compared with controls.

Aim 3: Examine the relationships between brain MRI and cognitive function in older persons
with HF and controls at baseline.

Hypothesis 3a: Decreased grey matter and perfusion in the temporal lobe and an increased
volume of white matter hyperintensities in the temporal lobe will be associated with
decreased memory scores.

Hypothesis 3b: Decreased grey matter and perfusion in the prefrontal cortex and an increased
volume of white matter hyperintensities in the prefrontal cortex will be associated with a
decreased executive function score.

Inclusion Criteria:

- 65 years old or older

- English speaking and writing;

- Stable guideline based medication regimen for at least four weeks prior to enrollment

- New York Heart Association classification I-IV

Exclusion Criteria:

- Mini-Mental Status Exam score equal to or less than 24;

- Current diagnosis of neurological illnesses or movement disorders (e.g. Alzheimer's
dementia, Parkinson's disease, Epilepsy);

- History of substance abuse/treatment;

- Untreated depression

- History of stroke;

- Hepatic insufficiency;

- Severe renal failure;

- Untreated anemia;

- Left ventricular assist device;

- History of the following within three months of study enrollment: acute myocardial
infarction, unstable angina, coronary artery bypass surgery, percutaneous transluminal
angioplasty, or biventricular pacemaker insertion;

- History of implantable device (or other MRI contraindications).

- Prisoners

- Pregnancy