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1.  Longitudinal 1H MRS changes in mild cognitive impairment and Alzheimer’s disease 
Neurobiology of aging  2006;28(9):1330-1339.
Magnetic Resonance (MR)- based volume measurements of atrophy are potential markers of disease progression in patients with amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD). Longitudinal changes in 1H MR spectroscopy (1H MRS) metabolite markers have not been characterized in aMCI subjects. Our objective was to determine the longitudinal 1H MRS metabolite changes in patients with aMCI, and AD, and to compare 1H MRS metabolite ratios and ventricular volumes in tracking clinical disease progression in AD. The neuronal integrity marker N-acetylaspartate/Creatine ratio declined in aMCI and AD patients compared to cognitively normal elderly. The changein 1H MRS metabolite ratios correlated with clinical progression about as strongly as the rate of ventricular expansion, suggesting that 1H MRS metabolite ratios may be useful markers for the progression of AD. Choline/Creatine ratio declined in stable aMCI, compared to converter aMCI patients and cognitively normal elderly, which may be related to a compensatory mechanism in aMCI patients who did not to progress to AD.
doi:10.1016/j.neurobiolaging.2006.06.018
PMCID: PMC2766807  PMID: 16860440
1H MR spectroscopy; 1H MRS; imaging; Alzheimer’s disease; mild cognitive impairment; serial; longitudinal; N-acetylaspartate; choline
2.  Visual Hallucinations in Posterior Cortical Atrophy 
Archives of neurology  2006;63(10):1427-1432.
Objective
To compare clinical and imaging features of patients with posterior cortical atrophy (PCA) with and without well-formed visual hallucinations.
Setting
Tertiary care medical center
Methods
Fifty-nine patients fulfilling criteria for PCA were retrospectively identified, and divided into two groups based on the presence (N=13) and absence (N=46) of visual hallucinations. Both groups were then compared statistically for clinical differences, as well as with voxel-based morphometry (VBM) for imaging differences.
Results
In PCA patients with hallucinations, parkinsonism and rapid eye movement sleep behavior disorder occurred more frequently (p<0.0001), as did myoclonic jerks (p=0.0002). VBM analysis showed greater atrophy in a network of structures, including the primary visual cortex, lentiform nuclei, thalamus, basal forebrain and midbrain in the patients with hallucinations.
Conclusions
Hallucinations in patients with PCA are associated with parkinsonism, rapid eye movement sleep behavior disorder, and myoclonic jerks. The results from the VBM analysis suggest that hallucinations in PCA cannot be exclusively attributed to atrophy of the posterior association cortices and may involve a circuit of thalamocortical connections.
doi:10.1001/archneur.63.10.1427
PMCID: PMC2748870  PMID: 17030659
Parkinsonism; Thalamus; Myoclonic jerks; REM sleep; Voxel based morphometry
3.  Clinicopathologic and Imaging Correlates of Progressive Aphasia and Apraxia of Speech 
Brain : a journal of neurology  2006;129(Pt 6):1385-1398.
Apraxia of speech (AOS) is a motor speech disorder characterized by slow speaking rate, abnormal prosody and distorted sound substitutions, additions, repetitions and prolongations, sometimes accompanied by groping and trial-and error articulatory movements. Although AOS is frequently subsumed under the heading of aphasia, and indeed most often co-occurs with aphasia, it can be the predominant or even the sole manifestation of a degenerative neurologic disease. In this study we determined whether the clinical classifications of aphasia and AOS correlated with pathological diagnoses and specific biochemical and anatomical structural abnormalities. Seventeen cases with initial diagnoses of a degenerative aphasia or AOS were reclassified independently by two speech-language pathologists — blinded to pathologic and biochemical findings - into one of five operationally defined categories of aphasia and AOS. Pathological diagnoses in the 17 cases were progressive supranuclear palsy in six, corticobasal degeneration in five, frontotemporal lobar degeneration with ubiquitin-only-immunoreactive changes in five, and Pick’s disease in one. Voxel-based morphometry and SPECT were completed, blinded to the clinical diagnoses, and clinico-imaging and clinico-pathological associations were then sought. Interjudge clinical classification reliability was 87% (κ =0.8) for all evaluations. Eleven cases had evidence of AOS, of which all (100%) had a pathological diagnosis characterized by underlying tau biochemistry, while five of the other six cases without AOS did not have tau biochemistry (p=0.001). A majority of the 17 cases had more than one yearly evaluation, demonstrating the evolution of the speech and language syndromes, as well as motor signs. Voxel-based morphometry revealed the premotor and supplemental motor cortices to be the main cortical regions associated with AOS, while the anterior peri-sylvian region was associated with non-fluent aphasia. Refining the classification of the degenerative aphasias and AOS may be necessary to improve our understanding of the relationships among behavioral, pathological, and imaging correlations.
doi:10.1093/brain/awl078
PMCID: PMC2748312  PMID: 16613895
Premotor cortex; supplementary motor cortex; progressive supranuclear palsy; apraxia of speech; aphasia
4.  Imaging Correlates of Posterior Cortical Atrophy 
Neurobiology of aging  2006;28(7):1051-1061.
The aim of this study was to compare patterns of cerebral atrophy on MRI, and neurochemistry on magnetic resonance spectroscopy (MRS), in subjects with posterior cortical atrophy (PCA) and typical Alzheimer's disease (AD). Voxel-based morphometry was used to assess grey matter atrophy in 38 subjects with PCA, 38 subjects with typical AD, and 38 controls. Clinical data was assessed in all PCA subjects. Single-voxel 1H MRS located in the posterior cingulate was analyzed in a subset of subjects with PCA, typical AD, and control subjects. PCA showed a pattern of atrophy affecting occipital, parietal and posterior temporal lobes, compared to controls. The pattern was bilateral, but more severe on the right. Subjects with PCA showed greater atrophy in the right visual association cortex than subjects with typical AD, whereas those with AD showed greater atrophy in the left hippocampus than those with PCA. 1H MRS suggested loss of neuronal integrity and glial activation in subjects with PCA and AD. The differing patterns of atrophy on MRI suggest that PCA should be considered a distinct entity from typical AD.
doi:10.1016/j.neurobiolaging.2006.05.026
PMCID: PMC2734142  PMID: 16797786
Posterior cortical atrophy; Alzheimer's disease; voxel-based morphometry; magnetic resonance imaging; magnetic resonance spectroscopy
5.  Argyrophilic Grains: A Distinct Disease or an additive Pathology? 
Neurobiology of aging  2006;29(4):566-573.
Background
Argyrophilic grains (AG) are silver-positive spindle shaped lesions found at postmortem. Their significance is controversial.
Objective
To determine clinical correlates of AG and MRI signature patterns of atrophy that could allow premortem recognition of this pathology.
Methods
Cases with AG were identified from a longitudinal study of aging and dementia. Clinical features were compared between subjects with and without dementia. Voxel-based morphometry (VBM) was used to assess patterns of grey matter atrophy in subjects compared to controls. Whole brain volumes (WBV) were compared across groups.
Results
Twenty-two cases (14 females; median age at death of 90 years; range: 70–101) with AG were identified. Eight of the 22 were demented. Those with dementia had higher median Braak (p=0.02) and lower MMSE (p=0.002). VBM demonstrated hippocampal atrophy in those with dementia (N=3) but no atrophy in those without (N=9). There was no difference in WBV between groups.
Conclusion
AG is a feature of old age commonly occurring in non-demented subjects. In this age group, the presence of AG may reduce the threshold for dementia.
doi:10.1016/j.neurobiolaging.2006.10.032
PMCID: PMC2727715  PMID: 17188783
Voxel based morphometry; total intracranial volume; argyrophilic; MRI; volume loss; Alzheimer’s disease
6.  Voxel-based morphometry in autopsy proven PSP and CBD 
Neurobiology of aging  2006;29(2):280-289.
The aim of this study was to compare the patterns of grey and white matter atrophy on MRI in autopsy confirmed PSP and CBD, and to determine whether the patterns vary depending on the clinical syndrome. Voxel-based morphometry was used to compare patterns of atrophy in 13 PSP and 11 CBD subjects and 24 controls. PSP and CBD subjects were also subdivided into those with a dominant dementia or extrapyramidal syndrome. PSP subjects showed brainstem atrophy with involvement of the cortex and underlying white matter. Frontoparietal grey and subcortical grey matter atrophy occurred in CBD. When subdivided, PSP subjects with an extrapyramidal syndrome had more brainstem atrophy and less cortical atrophy than CBD subjects with an extrapyramidal syndrome. PSP subjects with a dementia syndrome had more subcortical white matter atrophy than CBD subjects with a dementia syndrome. These results show regional differences between PSP and CBD that are useful in predicting the underlying pathology, and help to shed light on the in vivo distribution of regional atrophy in PSP and CBD.
doi:10.1016/j.neurobiolaging.2006.09.019
PMCID: PMC2702857  PMID: 17097770
Progressive supranuclear palsy; corticobasal degeneration; magnetic resonance imaging; pathology; white matter; grey matter; dementia; parkinsonism; extrapyramidal

Results 1-6 (6)