Vasco Dos Santos

Reduced olfactory bulb and tract volume in early Alzheimer's disease—A MRI study

Olfactory dysfunction has been reported to occur already in the early stages of Alzheimers disease (AD) and to increase with disease severity. In neuropathological research, the deposition of neurofibrillary tangles and neuritic plaques in the olfactory bulb and tract (OBT) of AD patients has been consistently demonstrated. We used high-resolution magnetic resonance imaging (MRI) to determine the volume of the OBT in 21 patients with early AD and in 21 healthy comparison subjects. The OBT was manually traced on consecutive coronal slices. When compared to healthy controls, right, left and mean OBT volumes were significantly reduced in patients with AD (p<0.01). In AD patients, the mean OBT volume was significantly correlated with global cognitive performance as determined by the mini-mental state examination (r=0.605; p=0.004). Manual tracing on MRI images revealed OBT atrophy to be present early in the course of AD. Since the respective findings were associated with cognitive impairment, they may contribute to early recognition and diagnosis of the disease.

The cerebellum in mild cognitive impairment and Alzheimer’s disease – A structural MRI study

Neuropathological research consistently revealed the cerebellum to undergo degenerative changes in Alzheimers disease (AD). Whether these alterations affect cerebellar morphology in vivo has not yet been investigated in a comprehensive way. Magnetic resonance imaging was performed in 20 patients with AD, 20 with mild cognitive impairment (MCI), and 20 healthy controls. By manual tracing the cerebellum was divided in four substructures (anterior lobe, superior posterior lobe, inferior posterior lobe and corpus medullare, respectively) on each hemisphere. Posterior cerebellar lobes were significantly smaller in AD patients when compared to healthy controls. In the AD group, atrophy of the posterior cerebellar regions was associated with poorer cognitive performance. Our findings lend further support for cerebellar involvement in AD.

MRI-Derived Atrophy of the Olfactory Bulb and Tract in Mild Cognitive Impairment and Alzheimer's Disease

There is increasing histopathological evidence that the olfactory bulb and tract (OBT) is a primary focus of neurodegenerative changes in Alzheimers disease (AD). Correspondingly, high-resolution magnetic resonance imaging revealed significant atrophy of the OBT in manifest AD. Whether these alterations are already present in mild cognitive impairment, the assumed preclinical stage of AD, has not been investigated yet. OBT volumes were assessed by manual tracing in 29 patients with mild cognitive impairment, 27 patients with probable AD, and 30 healthy controls. In a second step, voxel based morphometry was used to investigate the potential association between OBT atrophy and morphological changes in other brain regions. Patients had significantly lower OBT volumes when compared to controls, with atrophy being most prominent in the AD group. In addition, OBT atrophy was associated with a decreased medial temporal lobe (MTL) gray matter density bilaterally. Our findings indicate that neurodegeneration in OBT and MTL regions is linked and suggest that OBT volume might be a surrogate marker in AD.

Clock drawing performance and brain morphology in mild cognitive impairment and Alzheimer’s disease

The Clock Drawing Test (CDT) is a widely used instrument in the neuropsychological assessment of Alzheimers disease (AD). As CDT performance necessitates several cognitive functions (e.g., visuospatial and constructional abilities, executive functioning), an interaction of multiple brain regions is likely. Fifty-one subjects with mild cognitive impairment, 23 with AD and 15 healthy controls underwent high-resolution magnetic resonance imaging. Optimized voxel-based morphometry (VBM) was performed to investigate the putative association between CDT performance and gray matter (GM) density throughout the entire brain. In the first step of analysis (p<.001, uncorrected), VBM revealed a reduced GM density in numerous cortical (temporal lobe, frontal lobe, parietal lobe, cerebellum) and subcortical (thalamus, basal ganglia) brain regions to be associated with poorer CDT performance. When corrected for multiple comparisons (p<.01), the associations remained significant predominantly in the left temporal and--less pronounced--the right temporal lobe. VBM demonstrated CDT performance to depend on the integrity of widely distributed cortical and subcortical areas in both brain hemispheres with accentuation in the left-sided temporal lobe region.

Morphological Cerebral Correlates of CERAD Test Performance in Mild Cognitive Impairment and Alzheimer's Disease

The objective of this study was to investigate the association between structural cerebral changes and neuropsychological deficits in mild cognitive impairment (MCI) and Alzheimers disease (AD). Sixty patients with MCI, 34 patients with mild to moderate AD, and 32 healthy controls underwent both extensive neuropsychological assessment (CERAD test battery) and high-resolution structural magnetic resonance imaging. We used optimized voxel based morphometry to investigate (i) differences in gray matter density between the three aforementioned groups and (ii) the putative relations of CERAD test performance with atrophic brain changes. When compared to the healthy controls, the AD patients and, to a lesser extent, patients with MCI showed significant density losses predominantly in the medial temporal lobe. Deficits in verbal fluency and word finding were significantly correlated with left fronto-temporal and left temporal (including hippocampal) changes, respectively. Decreased scores in immediate and delayed recall and in delayed recognition were associated with several cortical and subcortical sites including the parahippocampal and posterior cinguli gyri, the right thalamus, and the right hippocampus, whereas deficits in constructional praxis and constructional praxis recall referred to sites in the left thalamus and cerebellum, and the temporal cortices (bilaterally), respectively. Our findings lend further support for medial temporal lobe degeneration in MCI and AD and demonstrate that cognitive deficits as assessed on the CERAD do not simply refer to specific changes in discrete cerebral sites but rather reflect morphological alterations in widespread networks.

Apolipoprotein E polymorphism and brain morphology in mild cognitive impairment.

Background: The apolipoprotein E (ApoE) genotype has been confirmed as the major genetic risk factor for late-onset Alzheimer’s disease (AD). How the ApoE genotype and brain morphology relate to each other is only partly understood, particularly in mild cognitive impairment, the assumed prestage of AD. Methods: A total of 83 subjects with mild cognitive impairment (aging-associated cognitive decline criteria) were investigated with optimized voxel-based morphometry (VBM). We tested for differences in gray and white matter densities between groups according to their ApoE status, i.e. Ε4 allele noncarriers (n = 42), subjects with one Ε4 allele (n = 27) and subjects with two Ε4 alleles (n = 14). Results: In individuals carrying two Ε4 alleles, VBM revealed a decline in gray matter density predominantly in the medial temporal lobe region. Subjects with a single copy of the Ε4 allele exhibited gray matter atrophy in the right inferior frontal gyrus. With respect to white matter changes, atrophy was only found in subjects homozygous for Ε4 and confined to the right superior and middle temporal gyrus. Conclusion: Our findings support the hypothesis that the ApoE genotype in mild cognitive impairment might be associated with structural changes typically found in the early stages of AD.

P1-299: The cerebellum in mild cognitive impairment and Alzheimer's disease: A structural MRI study

Background: Neuropathological research consistently revealed the cerebellum to undergo degenerative changes in Alzheimer’s disease (AD). Whether these alterations affect cerebellar morphology in vivo has not yet been investigated in a comprehensive way. Methods: Magnetic resonance imaging was performed in 20 patients with AD, 20 with mild cognitive impairment (MCI), and 20 healthy controls. By manual tracing the cerebellum was divided in 4 substructures (anterior lobe, superior posterior lobe, inferior posterior lobe and corpus medullare, respectively) on each hemisphere. Results: Posterior cerebellar lobes were significantly smaller in AD patients when compared to healthy controls. In the AD group, atrophy of the posterior cerebellar regions was associated with poorer cognitive performance. Conclusions: Our findings lend further support for cerebellar involvement in AD.

P2-088: Apolipoprotein E polymorphism and brain morphology in mild cognitive impairment

Background: The Apolipoprotein E (ApoE) has been confirmed as the major genetic risk factor for late-onset Alzheimer’s disease (AD). How ApoE genotype and brain morphology relate to each other is only partly understood, particularly in mild cognitive impairment, the assumed prestage of AD. Methods: A total of 83 subjects with mild cognitive impairment were investigated with optimized voxel-based morphometry (VBM). We tested for differences in gray and white matter densities between groups according to their ApoE status, i.e. 4 allele noncarriers (n 42), subjects with one 4 allele (n 27), and subjects with two 4 alleles (n 14), respectively. Results: In individuals carrying two 4 alleles, VBM revealed a decline in gray matter density predominantly in the medial temporal lobe region. Subjects with a single copy of the 4 allele exhibited gray matter atrophy in right inferior frontal gyrus. With respect to white matter changes, atrophy was only found in subjects homozygous for 4 and confined to the right superior and middle temporal gyrus. Conclusions: Our findings support the hypothesis that the ApoE genotype in mild cognitive impairment might be associated with structural changes typically found in the early stages of AD.