Corticobasal Syndrome in a Family with Early-Onset Alzheimer's Disease Linked to a Presenilin-1 Gene Mutation.

BACKGROUND: Alzheimer's disease (AD) is the second-most frequent cause underlying corticobasal syndrome (CBS). However, a reliable diagnosis using clinical, neuropsychological, or neuroimaging approaches has not yet been achieved. METHODS: Clinical, neuropsychological, imaging, and neuropathology studies were undertaken in a large Spanish family with early-onset familial AD (EOFAD) carrying a Met233Leu mutation linked to presenilin-1 gene (PSEN-1). RESULTS: Two of three examined members of this family presented with the usual amnestic pattern. At the age of 47 years, a third family member, in whom pathology was later confirmed, developed prominent CBS combined with severe neuropsychiatric and behavioral disturbances resembling those often found in EOFAD. CONCLUSION: Although CBS in EOFAD appears to be rare, demonstration of a linkage to PSEN-1 gene mutations may permit in vivo diagnosis.

Persistence of cholinesterase inhibitor treatment in dementia: insights from a naturalistic study.

BACKGROUND: Cholinesterase inhibitors (ChEI) are widely used in dementia, but there is a lack of practice guidelines in case of intolerance or absence of perceived effect. METHODS: Two hundred and forty patients (mean age 77 years, SD 6.3, 66% female) with Alzheimer's disease or Lewy body dementia were prescribed a ChEI and evaluated annually under conditions of standard practice. Of these, 152 patients maintained, 36 switched, and 52 abandoned ChEI treatment. RESULTS: Less behavioural disturbance and less cognitive deterioration were observed, respectively, at the 3- and 4-year follow-up assessments in the patients who maintained the first prescribed ChEI (p < 0.05). Cognitive benefits were reinforced in the patients who experienced some adverse event, but no benefits were observed when the patient or caregiver did not perceive an effect. CONCLUSIONS: Maintenance of the first prescribed ChEI was supported when some benefit was perceived by the patient or caregiver, even in cases of nonserious adverse events.

Comparison of different methods of spatial normalization of FDG-PET brain images in the voxel-wise analysis of MCI patients and controls.

OBJECTIVE: One of the most interesting clinical applications of 18F-FDG PET imaging in neurodegenerative pathologies is that of establishing the prognosis of patients with mild cognitive impairment (MCI), some of whom have a high risk of progressing to Alzheimer's disease (AD). One method of analyzing these images is to perform statistical parametric mapping (SPM) analysis. Spatial normalization is a critical step in such an analysis. The purpose of this study was to assess the effect of using different methods of spatial normalization on the results of SPM analysis of 18F-FDG PET images by comparing patients with MCI and controls. METHODS: We evaluated the results of three spatial normalization methods in an SPM analysis by comparing patients diagnosed with MCI with a group of control subjects. We tested three methods of spatial normalization: MRI-DARTEL and MRI-SPM8, which combine structural and functional images, and FDG-SPM8, which is based on the functional images only. RESULTS: The results obtained with the three methods were consistent in terms of the main pattern of functional alterations detected; namely, a bilateral reduction in glucose metabolism in the frontal and parietal cortices in the patient group. However, MRI-SPM8 also revealed differences in the left temporal cortex, and MRI-DARTEL revealed further differences in the left temporal cortex, precuneus, and left posterior cingulate. CONCLUSIONS: The results obtained with MRI-DARTEL were the most consistent with the pattern of changes in AD. When we compared our observations with those of previous reports, MRI-SPM8 and FDG-SPM8 seemed to show an incomplete pattern. Our results suggest that basing the spatial normalization method on functional images only can considerably impair the results of SPM analysis of 18F-FDG PET studies.

Alzheimer's disease with vascular component: a distinct clinical entity?

BACKGROUND: Longitudinal reports on the clinical features of patients with Alzheimer's disease (AD) and concomitant cerebrovascular disease are scarce. METHODS: We elaborated a working definition of AD with vascular component (ADVC), and this definition was retrospectively investigated in a cohort of patients with cognitive deterioration who were prescribed a cholinesterase inhibitor during usual practice. RESULTS: A total of 137 patients with probable AD and 66 patients with ADVC were studied during a mean follow-up period of 2.8 years. Univariate analyses demonstrated worse functional evolution and anticipation of psychotic symptoms and agitation in the ADVC group. CONCLUSIONS: The present results are consistent with an additive model of predominantly frontal-subcortical vascular damage in AD.