| Abstract |
Background. White matter (WM) changes, including myelin breakdown, have been reported in Alzheimer’s disease (AD) and mild cognitive impairment (MCI) and both conditions are associated with increased comorbidity with late-life depression. The nature of NAWM changes associated with normal aging, dementia, depression and/or MCI has not been systematically investigated using measures particularly sensitive to regional myelin integrity.
Multiexponential T2 (MET2) imaging calculates short T2 and myelin water fraction (MWF) values, strongly correlated with histological measures of myelin. In the present study a multi-echo, spin-echo (MESE) sequence was utilized to examine myelin content as a function of age and severity of neuropsychiatric impairment in patients diagnosed with AD or MCI and cognitively intact elders.
Methods. Measurements of Short T2, Long T2 and MWF values were obtained within 12 NAWM areas in patients and controls, involving periventricular and deep frontal, parietal, temporal and occipital WM, separately in each hemisphere, as well as the genu and splenium of the Corpus Callosum (CC) in patients diagnosed with probable AD (n=25) or MCI (n=43) and cognitively intact elderly controls (n=33). All participants received a comprehensive neuropsychological and neuropsychiatric assessment.
Results. AD patients displayed higher age-adjusted long and short T2 values and reduced MWF values in left temporal/parietal and bilateral periventricular NAWM than controls and MCI patients. Preliminary analyses revealed significantly increased Long and Short T2 values with age in the majority of ROIs in the NI and MCI groups. With few exceptions, corresponding reductions in MWF values were also found. Age-related effects in the Dementia group were restricted to the left temporal (Long T2) and periventricular NAWM (Short T2).
Short T2/MWF values in temporal, frontal, and periventricular NAWM of controls and/or MCI patients were significantly associated with episodic and semantic memory performance and depressive symptomatology. In addition, the impact of age on memory performance was significantly mediated by age-related changes in short T2 and MWF values in these regions.
Discussion. To our knowledge, this is the first study utilizing the Multi-echo T2 relaxation time technique to improve specificity in detecting myelin degradation, predominantly in left hemisphere temporal, parietal and periventricular NAWM, even in mild dementia. WM and myelin changes have been documented in age-related neurodegenerative disorders, such as AD and MCI, and potentially precede amyloid and tau pathology. Moreover, age-related demyelination was associated with reduced memory function and increased depression symptom severity in an anatomically specific manner. This effect was more pronounced for episodic memory function in prodromal dementia states (MCI). These changes suggest an important role of WM integrity in clinical and neuropsychiatric manifestations of these patients.
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Myelin content changes in probable Alzheimer’s disease and mild cognitive impairment
