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The retrogenesis model of Alzheimer's disease (AD) posits that white matter (WM) degeneration follows a pattern that is the reverse of myelogenesis. Using diffusion tensor imaging (DTI) to test this model, we predicted greater loss of microstructural integrity in late-myelinating WM fiber pathways in AD patients than in healthy older adults, whereas differences in early-myelinating WM fiber pathways were not expected. We compared 16 AD patients and 14 demographically-matched healthy older adults with a whole-brain approach via tract-based spatial statistics (TBSS), and a region of interest (ROI) approach targeting early-myelinating (posterior limb of internal capsule, cerebral peduncles) and late-myelinating (inferior longitudinal fasciculus [ILF], superior longitudinal fasciculus [SLF]) fiber pathways. Permutation-based voxelwise analysis supported the retrogenesis model. There was significantly lower fractional anisotropy (FA) in AD patients compared to healthy older adults in late-myelinating but not early-myelinating pathways. These group differences appeared to be driven by loss of myelin integrity based on our finding of greater radial diffusion in AD than in healthy elderly. ROI analyses were generally in agreement with whole-brain findings, with significantly lower FA and increased radial diffusion in the ILF in the AD group. Consistent with the retrogenesis model, AD patients showed demonstrable changes in late-myelinating WM fiber pathways. Given greater change in the ILF than the SLF, wallerian degeneration secondary to cortical atrophy may also be a contributing mechanism. Knowledge of the pattern of WM microstructural changes in AD and its underlying mechanisms may contribute to earlier detection and intervention in at-risk groups.

Background and Purpose: Associations between regional white matter lesion pathology and neuropsychological performance across the aging spectrum are not well understood and, to date, research has been largely contradictory and inconclusive. The current study set out to clarify some of the inconsistencies in the literature by relating volumetric analyses of white matter lesions (deep white matter lesions and periventricular lesions) to neuropsychological performance in a large clinical sample of older adults diagnosed with mild cognitive impairment., Methods: Seventy older adults with mild cognitive impairment were administered a comprehensive neuropsychological battery. White matter lesions identified on T2-weighted FLAIR images were quantified using a semi-automated volumetric approach (pixel thresholding)., Results: Results showed that, in contrast to performance on memory and naming tasks, total white matter lesions strongly predicted executive impairments, slowed processing speed, and visuospatial/construction difficulties. In addition, separate regression analyses demonstrated that results were primarily accounted for by deep white matter lesions (but not periventricular lesions), most likely due to frontal-subcortical circuitry disruption. Moreover, deep white matter lesions, but not periventricular lesions, significantly predicted overall poorer neuropsychological functioning after controlling for age, education, and level of depression., Conclusions: Taken together, findings demonstrate a differential influence of lesion type on cognitive impairment in mild cognitive impairment and implicate deep white matter lesions as being most detrimental in terms of neuropsychological functioning. Clinical, theoretical, and methodological implications of these results are discussed.

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]

We investigated associations between DTI indices of three brainstem white matter tracts, traumatic brain injury (TBI) injury characteristics, and postconcussive symptomatology (PCS) in a well-characterized sample of veterans with history of mild to moderate TBI (mTBI). 58 military veterans (mTBI: n = 38, mean age = 33.2, mean time since injury = 90.9 months; military controls [MC]; n = 20; mean age = 29.4) were administered 3T DTI scans as well as a comprehensive neuropsychiatric evaluation including evaluation of TBI injury characteristics and PCS symptoms (e.g., negative mood, dizziness, balance and coordination difficulties). Tractography was employed by seeding ROIs along 3 brainstem white matter tracts (i.e., medial lemniscus-central tegmentum tract [ML-CTT]; corticospinal tracts [CST], and pontine tegmentum [PT]), and mean DTI values were derived from fractional anisotropic (FA) maps. Results showed that there were no significant difference in FA between the MC and TBI groups across the 3 regions of interest; however, among the TBI group, CST FA was significantly negatively associated with LOC duration. Additionally, lower FA of certain tracts-most especially the PT-was significantly associated with increased PCS symptoms (i.e., more severe vestibular symptoms, poorer physical functioning, and greater levels of fatigue), even after adjusting for PTSD symptoms. Our findings show that, in our sample of veterans with mTBI, tractography-based DTI indices of brainstem white matter tracts of interest are related to the presence and severity of PCS symptoms. Findings are promising as they show linkages between brainstem white matter integrity and injury severity (LOC), and they raise the possibility that the pontine tegmentum in particular may be a useful marker of PCS symptoms. Collectively, these data point to important neurobiological substrates of the chronic and complex constellation of symptoms following the 'signature injury' of our combat-exposed veterans. [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]