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Medial temporal lobe and temporoparietal brain regions are among the earliest neocortical sites to undergo pathophysiologic alterations in Alzheimer's disease (AD), although the underlying white matter changes in these regions is less well known. We employed diffusion tensor imaging to evaluate early alterations in regional white matter integrity in participants diagnosed with mild cognitive impairment (MCI). The following regions of interests (ROIs) were examined: 1) anterior cingulum (AC); 2) posterior cingulum (PC); 3) genu of the corpus callosum; 4) splenium of the corpus callosum; and 5) as a control site for comparison, posterior limb of the internal capsule. Forty nondemented participants were divided into demographically-similar groups based on cognitive status (MCI: n = 20; normal control: n = 20), and fractional anisotropy (FA) estimates of each ROI were obtained. MCI participants showed greater posterior white matter (i.e., PC, splenium) but not anterior white matter (i.e., AC, genu) changes, after adjusting for age, stroke risk, and whole brain volume. FA differences of the posterior white matter were best accounted for by changes in radial but not axial diffusivity. PC FA was also significantly positively correlated with hippocampal volume as well as with performance on tests of verbal memory, whereas stroke risk was significantly correlated with genu FA and was unrelated to PC FA. When investigating subtypes of our MCI population, amnestic MCI participants showed lower PC white matter integrity relative to those with non-amnestic MCI. Findings implicate involvement of posterior microstructural white matter degeneration in the development of MCI-related cognitive changes and suggest that reduced FA of the PC may be a candidate neuroimaging marker of AD risk. [ABSTRACT FROM AUTHOR]

Elevated pulse pressure (PP) is associated with cognitive decline and increased risk of Alzheimer's disease (AD) in older adults, although the mechanisms behind these associations remain unclear. To address this question, we examined whether antemortem late-life PP elevation predicted vascular or AD pathology in autopsy-confirmed AD patients. Sixty-five elderly patients (mean age 74.2 years) clinically diagnosed with possible or probable AD underwent neuropsychological testing and blood pressure examinations. Postmortem histopathological measures of cerebrovascular disease (CVD) and AD neuropathology were later obtained on these same patients. We expected that antemortem PP elevation, but not standard blood pressure measures such as systolic or diastolic blood pressure, would predict the autopsy-based presence of CVD, and possibly AD pathology, in elderly AD patients. Results demonstrated that antemortem PP elevation was associated with the presence and severity of CVD at autopsy. For every 5 mmHg increase in antemortem PP there was an estimated 36% increase in the odds of having CVD at autopsy. Additionally, PP accounted for 12% of variance in CVD severity. No significant associations were present for cerebral amyloid angiopathy or Braak and Braak staging of the severity of AD pathology. Other standard blood pressure measures also did not significantly predict neuropathology. The association between antemortem PP and CVD at autopsy suggests that in older adults with AD, PP elevation may increase the risk of CVD. These findings may have treatment implications since some antihypertensive medications specifically address the pulsatile component of blood pressure (e.g., renin-angiotensin system inhibitors, calcium channel blockers). [ABSTRACT FROM AUTHOR]

Background: Difficulty providing accurate diagnosis and prognosis, especially after mild forms of traumatic brain injury (TBI), has increased efforts to detect changes in white matter microstructure using advanced neuroimaging techniques. Although methods such as diffusion tensor imaging (DTI) have greatly increased knowledge of white matter changes resulting from TBI, several shortcomings limit the utility of these techniques particularly when applied to populations with mild TBI (mTBI) history.In vivoimaging of myelin may be particularly well suited to detect changes in white matter microstructure resulting from mTBI. Review: This manuscript will briefly review the animal and histological data supporting the important role of myelin following TBI, contributions and shortcomings of the use of diffusion tensor imaging (DTI) in mild TBI and the utility of multi-component relaxometry (MCR) techniques as a method for improved visualizing of white matter microstructural integrity in myelin. Conclusion: The use of MCR-based techniques has potential as a clinical and research tool to assess and track changes in myelin as well as the common behavioural changes such as slowed processing speed following TBI. [ABSTRACT FROM AUTHOR]

Objective Lesions to the retrosplenial cortex secondary to acute stroke or tumor have been shown to disrupt Papez's circuit due to disconnection between the anterior thalamus and hippocampus, via the posterior cingulate, producing an amnestic syndrome. This case demonstrates how small but strategic lacunes in this region may produce memory deficits. Method The patient is a 52-year-old, right-handed, African-American woman with 18 years of education who reported memory changes over the last 8 years (e.g. misplacing items, forgetting details of conversations). Her medical history was notable for BMI of 31 and borderline diabetes. She completed structural magnetic resonance imaging 6 years prior to, and concordant with, her neuropsychological evaluation. Both scans showed two small (2-3 mm) right-sided retrosplenial lacunes, without evidence of hippocampal or global volume loss over the 6-year span. Results Her neurocognitive profile was characterized by impairments in both verbal (stories, word-list) and figural memory, with relative strengths in attention, processing speed, and executive functioning. Across memory measures, she performed in the low average-to-mildly impaired range on immediate recall, mildly-to-severely impaired range on delayed recall, and did not benefit from yes-no recognition format. She demonstrated additional features of an amnestic profile, including flat learning slope, recency effect, elevated cued recall intrusion errors, and very elevated false positive errors on recognition. Conclusions Findings expand upon the existing literature to show that chronic, small retrosplenial lacunes can disrupt the connection between the anterior thalamus and hippocampus, resulting in a clinical presentation of circumscribed memory impairment that persists years beyond acute vascular changes. [ABSTRACT FROM AUTHOR]