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D H Salat

Publications and source records attributed to D H Salat.

9 recordsLinked to original sources

Neuroimaging H.M.: a 10-year follow-up examination.

In 1997, Corkin et al. described the anatomical boundaries of the amnesic patient H.M.'s surgical resection, based on a comprehensive analysis of magnetic resonance imaging (MRI) scans collected in 1992 and 1993 (Corkin et al. (1997) J Neurosci 17:3964-3979). We subsequently scanned H.M. on several occasions, employing more advanced data acquisition and analysis methods, and now describe additional details about his brain anatomy and pathology. This account combines results from high-resolution T1-weighted scans, which provide measures of cortical and subcortical morphometry, diffusion tensor images, which provide quantitative information about white matter microstructure and the anatomy of major fasciculi, and T2-weighted images, which highlight damage to deep white matter. We applied new MRI analysis techniques to these scans to assess the integrity of areas throughout H.M.'s brain. We documented a number of new changes, including cortical thinning, atrophy of deep gray matter structures, and a large volume of abnormal white matter and deep gray matter signal. Most of these alterations were not apparent in his prior scans, suggesting that they are of recent origin. Advanced age and hypertension likely contributed to these new findings.

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Increased hippocampal activation in mild cognitive impairment compared to normal aging and AD.

OBJECTIVE: To use fMRI to investigate whether hippocampal and entorhinal activation during learning is altered in the earliest phase of mild cognitive impairment (MCI). METHODS: Three groups of older individuals were studied: 10 cognitively intact controls, 9 individuals at the mild end of the spectrum of MCI, and 10 patients with probable Alzheimer disease (AD). Subjects performed a face-name associative encoding task during fMRI scanning, and were tested for recognition of stimuli afterward. Data were analyzed using a functional-anatomic method in which medial temporal lobe (MTL) regions of interest were identified from each individual's structural MRI, and fMRI activation was quantified within each region. RESULTS: Significantly greater hippocampal activation was present in the MCI group compared to controls; there were no differences between these two groups in hippocampal or entorhinal volumes. In contrast, the AD group showed hippocampal and entorhinal hypoactivation and atrophy in comparison to controls. The subjects with MCI performed similarly to controls on the fMRI recognition memory task; patients with AD exhibited poorer performance. Across all 29 subjects, greater mean entorhinal activation was found in the subgroup of 13 carriers of the APOE epsilon4 allele than in the 16 noncarriers. CONCLUSIONS: The authors hypothesize that there is a phase of increased medial temporal lobe activation early in the course of prodromal Alzheimer disease followed by a subsequent decrease as the disease progresses.

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Age-related changes in prefrontal white matter measured by diffusion tensor imaging.

Age-related degeneration of brain white matter (WM) has received a great deal of attention, with recent studies demonstrating that such changes are correlated with cognitive decline and increased risk for the development of age-related neurodegenerative disease. Past studies have used magnetic resonance imaging (MRI) to measure the volume of normal and abnormal tissue signal as an index of tissue pathology. More recently, diffusion tensor MRI (DTI) has been employed to obtain regional measures of tissue microstructure, such as fractional anisotropy (FA), providing better spatial resolution and potentially more sensitive metrics of tissue damage than traditional volumetric measures. We used DTI to examine the regional basis of age-related alterations in prefrontal WM. As expected from prior volumetric and DTI studies, prefrontal FA was reduced in older adults (OA) compared to young adults (YA). Although WM volume has been reported to be relatively preserved until late aging, FA was significantly reduced by middle age. Much of prefrontal WM showed reduced FA with increasing age. Ventromedial and deep prefrontal regions showed a somewhat greater reduction compared to other prefrontal areas. Prefrontal WM anisotropy correlated with prefrontal WM volume, but the correlation was significant only when the analysis was limited to participants over age 40. This evidence of widespread and regionally accelerated alterations in prefrontal WM with aging illustrates FA's potential as a microstructural index of volumetric measures.

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Age-related alterations in white matter microstructure measured by diffusion tensor imaging.

Cerebral white matter (WM) undergoes various degenerative changes with normal aging, including decreases in myelin density and alterations in myelin structure. We acquired whole-head, high-resolution diffusion tensor images (DTI) in 38 participants across the adult age span. Maps of fractional anisotropy (FA), a measure of WM microstructure, were calculated for each participant to determine whether particular fiber systems of the brain are preferentially vulnerable to WM degeneration. Regional FA measures were estimated from nine regions of interest in each hemisphere and from the genu and splenium of the corpus callosum (CC). The results showed significant age-related decline in FA in frontal WM, the posterior limb of the internal capsule (PLIC), and the genu of the CC. In contrast, temporal and posterior WM was relatively preserved. These findings suggest that WM alterations are variable throughout the brain and that particular fiber populations within prefrontal region and PLIC are most vulnerable to age-related degeneration.

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Regional and progressive thinning of the cortical ribbon in Huntington's disease.

BACKGROUND: Huntington's disease (HD) is a fatal and progressive neurodegenerative disease that is accompanied by involuntary movements, cognitive dysfunction, and psychiatric symptoms. Although progressive striatal degeneration is known to occur, little is known about how the disease affects the cortex, including which cortical regions are affected, how degeneration proceeds, and the relationship of the cortical degeneration to clinical symptoms. The cortex has been difficult to study in neurodegenerative diseases primarily because of its complex folding patterns and regional variability; however, an understanding of how the cortex is affected by the disease may provide important new insights into it. METHODS: Novel automated surface reconstruction and high-resolution MR images of 11 patients with HD and 13 age-matched subjects were used to obtain cortical thickness measurements. The same analyses were performed on two postmortem brains to validate these methods. RESULTS: Regionally specific heterogeneous thinning of the cortical ribbon was found in subjects with HD. Thinning occurred early, differed among patients in different clinical stages of disease, and appeared to proceed from posterior to anterior cortical regions with disease progression. The sensorimotor region was statistically most affected. Measurements performed on MR images of autopsy brains analyzed similarly were within 0.25 mm of those obtained using traditional neuropathologic methods and were statistically indistinguishable. CONCLUSIONS: The authors propose that the cortex degenerates early in disease and that regionally selective cortical degeneration may explain the heterogeneity of clinical expression in HD. These measures might provide a sensitive prospective surrogate marker for clinical trials of neuroprotective medications.

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Selective preservation and degeneration within the prefrontal cortex in aging and Alzheimer disease.

BACKGROUND: The prefrontal cortex (PFC) is a heterogeneous cortical structure that supports higher cognitive functions, including working memory and verbal abilities. The PFC is vulnerable to neurodegeneration with healthy aging and Alzheimer disease (AD). OBJECTIVE: We used volumetric magnetic resonance imaging to determine whether any region within the PFC is more vulnerable to deterioration with late aging or AD. METHODS: Volumetric analysis of PFC regions was performed on younger healthy elderly subjects (n = 26; 14 men and 12 women [mean age, 71.7 years] for aging analysis; 12 men and 14 women [mean age, 71.4 years] for AD analysis), oldest healthy elderly (OHE) subjects (n = 22 [11 men and 11 women]; mean age, 88.9 years), and patients with AD (n = 22 [12 men and 10 women]; mean age, 69.8 years). RESULTS: The OHE subjects had less PFC white matter than did young healthy elderly subjects. The orbital region was selectively preserved relative to other PFC regions in the OHE subjects. Subjects with AD had less total PFC gray matter than did age-matched healthy subjects and significantly less volume in the inferior PFC region only. CONCLUSIONS: Orbital PFC is selectively preserved in OHE subjects. In contrast, degeneration within the PFC with AD is most prominent in the inferior PFC region. Thus, degeneration within the PFC has a regionally distinct pattern in healthy aging and AD.

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Prefrontal gray and white matter volumes in healthy aging and Alzheimer disease.

OBJECTIVES: To quantify the contribution of gray and white matter volumes to total prefrontal volume in healthy aging. To determine if prefrontal tissue volumes distinguish healthy aging from Alzheimer disease (AD). DESIGN: Volumes of total prefrontal cortex, prefrontal gray matter, and prefrontal white matter were compared among young healthy elderly (YHE) (n = 14; mean age, 70 years), old healthy elderly (OHE) (n = 14; mean age, 90 years), and subjects with AD (n = 14; mean age, 70 years) by analysis of variance. Additionally, Pearson correlations were performed between volumes and age. RESULTS: Old healthy elderly and subjects with AD had significantly less total prefrontal volume (approximately 15% less in both groups) and prefrontal white matter volume (approximately 30% less and 20% less in the OHE and AD groups, respectively) than YHE, but there were no differences between the OHE and AD groups. There was a significant difference in gray-white matter volume ratio with OHE having a higher ratio than YHE. Subjects with AD did not differ from YHE or OHE in this ratio. There were significant negative correlations between age and total prefrontal volume and age and prefrontal white matter volume in the healthy subjects. CONCLUSIONS: In the very old, the decline of white matter volume is disproportionately greater than the decline of gray matter volume. In subjects with AD both gray and white matter loss contribute to the decline of prefrontal volume. This is demonstrated by the gray-white matter ratio that does not differ between YHE and subjects with AD. Thus, it is likely that AD is different from accelerated aging.

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Sex differences in prefrontal volume with aging and Alzheimer's disease.

We used volumetric magnetic resonance imaging to examine sex differences in prefrontal tissue volumes of healthy aged and patients with Alzheimer's disease (AD). Healthy subjects had greater total prefrontal volume than AD, and men had greater total prefrontal volume than women (ps < or = 0.02). This was true for both gray and white matter volumes. There were no interactions between group and sex for total prefrontal volume. An exploratory analysis of each group suggested that sex differences in both gray and white matter in healthy aging are not sustained in AD.

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