Authors: Makovac, Elena | Serra, Laura | Spanò, Barbara | Giulietti, Giovanni | Torso, Mario | Cercignani, Mara | Caltagirone, Carlo | Bozzali, Marco
Article Type: Research Article
Abstract: Behavioral disorders and psychological symptoms (BPSD) in Alzheimer’s disease (AD) are known to correlate with grey matter (GM) atrophy and, as shown recently, also with white matter (WM) damage. WM damage and its relationship with GM atrophy are reported in AD, reinforcing the interpretation of the AD pathology in light of a disconnection syndrome. It remains uncertain whether this disconnection might account also for different BPSD observable in AD. Here, we tested the hypothesis of different patterns of association between WM damage of the corpus callosum (CC) and GM atrophy in AD patients exhibiting one of the following BPSD clusters: …Mood (i.e., anxiety and depression; ADmood ), Frontal (i.e., dishinibition and elation; ADfrontal ), and Psychotic (delusions and hallucinations; ADpsychotic ) related symptoms, as well as AD patients without BPSD. Overall, this study brings to light the strict relationship between WM alterations in different parts of the CC and GM atrophy in AD patients exhibiting BPSD, supporting the hypothesis that such symptoms are likely to be caused by characteristic patterns of neurodegeneration of WM and GM, rather than being a reactive response to accumulation of cognitive disabilities, and should therefore be regarded as potential markers of diagnostic and prognostic value in AD. Show more
Keywords: Alzheimer’s disease, behavioral, grey matter, magnetic resonance imaging, white matter
DOI: 10.3233/JAD-150612
Citation: Journal of Alzheimer's Disease, vol. 50, no. 2, pp. 591-604, 2016
Authors: Serra, Laura | Cercignani, Mara | Mastropasqua, Chiara | Torso, Mario | Spanò, Barbara | Makovac, Elena | Viola, Vanda | Giulietti, Giovanni | Marra, Camillo | Caltagirone, Carlo | Bozzali, Marco
Article Type: Research Article
Abstract: This longitudinal study investigates the modifications in structure and function occurring to typical Alzheimer’s disease (AD) brains over a 2-year follow-up, from pre-dementia stages of disease, with the aim of identifying biomarkers of prognostic value. Thirty-one patients with amnestic mild cognitive impairment were recruited and followed-up with clinical, neuropsychological, and MRI assessments. Patients were retrospectively classified as AD Converters or Non-Converters, and the data compared between groups. Cross-sectional MRI data at baseline, assessing volume and functional connectivity abnormalities, confirmed previous findings, showing a more severe pattern of regional grey matter atrophy and default-mode network disconnection in Converters than in Non-Converters. …Longitudinally, Converters showed more grey matter atrophy in the frontotemporal areas, accompanied by increased connectivity in the precuneus. Discriminant analysis revealed that functional connectivity of the precuneus within the default mode network at baseline is the parameter able to correctly classify patients in Converters and Non-Converters with high sensitivity, specificity, and accuracy. Show more
Keywords: Alzheimer’s disease, functional disconnection, grey matter atrophy, longitudinal study, mild cognitive impairment
DOI: 10.3233/JAD-150961
Citation: Journal of Alzheimer's Disease, vol. 51, no. 2, pp. 377-389, 2016
Authors: Serra, Laura | Giulietti, Giovanni | Cercignani, Mara | Spanò, Barbara | Torso, Mario | Castelli, Diana | Perri, Roberta | Fadda, Lucia | Marra, Camillo | Caltagirone, Carlo | Bozzali, Marco
Article Type: Research Article
Abstract: This study investigates whether different patterns of grey matter (GM) loss may account for the different neuropsychological profiles observed in patients with amnestic (a-) and non-amnestic (na-) mild cognitive impairment (MCI), and may predict patients' clinical evolution. Fifty-five consecutive individuals complaining of cognitive dysfunction (referred to specialist dementia clinics) were screened and included in the study if they met the diagnostic criteria for MCI on a neurodegenerative basis. After an extensive neuropsychological assessment, patients were classified as suffering from a-MCI or na-MCI. Twenty-eight healthy individuals were also recruited and served as controls. All participants underwent magnetic resonance imaging at 3T, …including conventional images and volumetric scans. Volumetric data were processed using voxel-based morphometry to assess between-group differences in regional GM volumes and correlations with neuropsychological performances. When compared to controls, a-MCI patients showed prominent GM volume reductions in the medial temporal lobes, while those with na-MCI showed reduced GM volumes in the orbito-frontal cortex and basal ganglia. In a-MCI patients, significant associations were found between verbal long-term memory performance and GM volumes in the hippocampus. Conversely, in na-MCI patients, associations were found between scores at tests exploring executive functions and GM volumes in the orbito-frontal cortex. At one-year follow-up, conversions were recorded exclusively toward Alzheimer's disease (AD) in the a-MCI group, and toward non-AD dementia in the na-MCI group. This study confirms that MCI is a heterogeneous clinical identity including different neurodegenerative entities; specific patterns of regional GM loss appear to account for specific neuropsychological features and are likely to predict patients' clinical evolution. Show more
Keywords: Alzheimer's disease, amnestic mild cognitive impairment, magnetic resonance imaging, non-amnestic mild cognitive impairment, voxel-based morphometry
DOI: 10.3233/JAD-2012-121663
Citation: Journal of Alzheimer's Disease, vol. 33, no. 4, pp. 1157-1165, 2013
Authors: Serra, Laura | Fadda, Lucia | Perri, Roberta | Spanò, Barbara | Marra, Camillo | Castelli, Diana | Torso, Mario | Makovac, Elena | Cercignani, Mara | Caltagirone, Carlo | Bozzali, Marco
Article Type: Research Article
Abstract: Constructional apraxia (CA) is often, but not always, observed in patients with Alzheimer's disease (AD). CA is usually explained by impairment of either basic perceptual and motor abilities, or executive functions. This study aims to evaluate the structural correlates of CA in AD. Forty-eight patients with AD and 20 healthy age-matched controls underwent a thorough neuropsychological investigation and an MRI scan to collect high-resolution T1-weighted data. Patients were classified as having (ADca) or not having (ADnonca) CA based on performance on the Freehand copying of drawings task. T1-weighted volumes were process according to the voxel based morphometry protocol, to assess …the presence of significant differences in local to grey matter volumes in patients compared to controls and in ADca compared to ADnonca. Post-hoc, the mean grey matter volume of clusters that resulted significantly different between groups was regressed against the neuropsychological scores in which the two patient groups performed differently. A pre-senile disease onset was significantly more frequent in patients with CA compared to ADnonca. ADca patients also showed worse performances than patients with ADnonca at some tests requiring the processing of visuo-spatial data and testing working memory. They also showed widespread reductions in grey matter volume, mainly located in areas known to be implicated in object recognition and localization, and in maintenance and re-orienting of spatial attention. These findings suggest that the occurrence of CA in AD is often associated with a peculiar clinical onset (i.e., pre-senile), neuropsychological profile, and distribution of grey matter atrophy. Show more
Keywords: Alzheimer's disease, constructional praxis, drawing tasks, voxel-based morphometry
DOI: 10.3233/JAD-130656
Citation: Journal of Alzheimer's Disease, vol. 38, no. 2, pp. 391-402, 2014
Authors: Bozzali, Marco | Dowling, Claire | Serra, Laura | Spanò, Barbara | Torso, Mario | Marra, Camillo | Castelli, Diana | Dowell, Nicholas G. | Koch, Giacomo | Caltagirone, Carlo | Cercignani, Mara
Article Type: Research Article
Abstract: One factor believed to impact brain resilience to the pathological damage of Alzheimer's disease (AD) is the so-called “cognitive reserve” (CR). A critical issue that still needs to be fully understood is the mechanism by which environmental enrichment interacts with brain plasticity to determine resilience to AD pathology. Previous work using PET suggests that increased brain connectivity might be at the origin of the compensatory mechanisms implicated in this process. This study aims to further clarify this issue using resting-state functional MRI. Resting-state functional MRI was collected for 11 patients with AD, 18 with mild cognitive impairment (MCI), and 16 …healthy controls, and analyzed to isolate the default mode network (DMN). A quantitative score of CR was obtained by combining information about number of years of education and type of schools attended. Consistent with previous reports, education was found to modulate functional connectivity in the posterior cingulate cortex, whose disconnection with the temporal lobes is known to be critical for the conversion from MCI to AD. This effect was highly significant in AD patients, less so in patients with MCI, and absent in healthy subjects. These findings show the potential neural mechanisms underlying the individual's ability to cope with brain damage, although they should be treated with some caution based on small numbers. Show more
Keywords: Alzheimer's disease, cognitive reserve, mild cognitive impairment, resting-state functional MRI
DOI: 10.3233/JAD-141824
Citation: Journal of Alzheimer's Disease, vol. 44, no. 1, pp. 243-250, 2015
