Lucia Fadda

The Mental Deterioration Battery: Normative Data, Diagnostic Reliability and Qualitative Analyses of Cognitive Impairment

This study aimed at investigating the clinical usefulness of the Mental Deterioration Battery (MDB) in the neuropsychological diagnosis and characterization of the dementia syndrome. In this paper, we report: (a) normative data for various test scores derived from the analysis of performance of 340 normal subjects living in urban areas; (b) an evaluation of the reliability of the single tests and of the battery as a whole in differentiating normal subjects from patients affected by cognitive deterioration derived from the analysis of performance of 130 normal subjects living in rural areas and 134 patients affected by probable Alzheimers dementia; (c) a cluster analysis of performances of the 340 normal subjects in the standardization group to evaluate possible criteria of homogeneity according to which the various MDB scores tend to aggregate; (d) an analysis of performance profiles of 183 patients with right monohemispheric focal lesions, 159 patients with left unilateral lesions with aphasia and 131 left-lesioned nonaphasic patients to evaluate the specificity of the single tests of the battery in documenting a selective impairment of one of the two cerebral hemispheres. Results confirm the reliability of the MBD in discriminating between normal and demented patients and provide indications for use of the battery in differentiating qualitative patterns of cognitive impairment.

Recognition memory for single items and for associations in amnesic patients.

Recognition memory performance reflects two distinct processes or types of memory referred to as recollection and familiarity. According to theoretical claims about the two types of memory, single item and associative recognition tasks can be used as an experimental method to distinguish recollection and familiarity processes. Associative recognition decisions can be used as an index of recollection while memory for single items is mostly based on familiarity judgement. We employed this procedure to examine a possible dissociation in the memory performance of amnesic patients between spared single item and impaired associative recognition. Twelve amnesic patients, six with damage confined to the hippocampus proper, and six with damage elsewhere in the brain, were recruited for the present study. The findings showed that hippocampal amnesics exhibit relative sparing of single item learning but are consistently deficient in the learning of all kinds of between-item associations. These results are consistent with the view that hippocampal formation contributes differently to declarative tasks that require recollective or familiarity processes.

Grey and White Matter Changes at Different Stages of Alzheimer's Disease

This study investigates abnormalities of grey (GM) and white matter (WM) in Alzheimers disease (AD), by modeling the AD pathological process as a continuous course between normal aging and fully developed dementia, with amnesic mild cognitive impairment (aMCI) as an intermediate stage. All subjects (9 AD, 16 aMCI patients, and 13 healthy controls) underwent a full neuropsychological assessment and an MRI examination at 3 Tesla, including a volumetric scan and diffusion tensor (DT)-MRI. The volumes were processed to perform a voxel-based morphometric analysis of GM and WM volume, while DT-MRI data were analyzed using tract based spatial statistics, to estimate changes in fractional anisotropy and mean diffusivity data. GM and WM volume and mean diffusivity and fractional anisotropy were compared across the three groups, and their correlation with cognitive functions was investigated. While AD presented a pattern of widespread GM atrophy, tissue loss was more subtle in patients with aMCI. WM atrophy was mainly located in the temporal lobe, but evidence of WM microscopic damage, assessed by DT-MRI, was also observable in the thalamic radiations and in the corpus callosum. Memory and executive functions correlated with either GM volume or fractional anisotropy in fronto-temporal areas. In conclusion, this study shows a comprehensive assessment of the brain tissue damage across AD evolution, providing insights on different pathophysiological mechanisms (GM atrophy, Wallerian degeneration, and brain disconnection) and their possible association with clinical aspects of cognitive decline.

Episodic memory impairment in patients with Alzheimer's disease is correlated with entorhinal cortex atrophy: A voxel-based morphometry study

The aims of this study were to investigate the pattern of cortical atrophy and the relationships between memory performances and the brain regions in Alzheimer’s Disease (AD). optimized voxel-based morphometry (VBM) was applied to the MRI brain images of 18 probable AD and 18 healthy subjects (HS). Patients performed verbal and visuo-spatial episodic and shortterm memory tests. Contrasting of AD group with HS, and anatomobehavioural correlations were carried out in order to identify regional atrophic changes and neuro-cognitive aspects in AD group. We found evidence of gray matter (GM) volume reduction in AD in the medial temporal, parietal and frontal areas bilaterally and in the left anterior thalamic nuclei. Performance on the episodic memory delayed recall tests co-varied with GM volume in the left entorhinal cortex. The pattern of cortical atrophy likely reflects the heterogeneous level of dementia severity in our AD group. The anatomical region affected in the left hemisphere indicates a sufferance at multiple levels of the Polysynaptic Hippocampal Pathway, which is involved in declarative memory. Findings on the entorhinal cortex and the delayed memory scores support the role of the entorhinal cortex in episodic memory. Damage to the entorhinal cortex, deafferenting the hippocampus from neocortical inputs, interferes with episodic memory consolidation in AD patients.

Cognition and behaviour are independent and heterogeneous dimensions in Alzheimer’s disease

Abstract.Clinical expressions of cognition and behaviour in Alzheimer’s disease (AD) patients are heterogeneous. Therefore, assessing the entire range of selective cognitive and behavioural characteristics of dementia in minute detail is extremely important. However, considering that groups of different symptoms may respond to the same pharmacological agent, it is also evident that a correct evaluation of the behaviour requires the grouping of symptoms in fewer syndromes. Thus, the authors have analysed various connections between selective cognitive domains and behavioural symptoms (BPSD) in probable AD outpatients. Two hundred and forty four patients with diagnosis of probable AD, according to DSM-IV and NINCDS-ADRDA criteria were enrolled. The evaluation included the Mini Mental State Examination, the Mental Deterioration Battery, and the Neuropsychiatric Inventory. Treatment with low doses of neuroleptic drugs only was allowed. Principal component analysis condensed the 18 cognitive/behavioural variables in 7 factors namely general-cognitive, constructional abilities, hyperactivity, psychosis, anxiety, mood-excitement and mood-depression/apathy. None of the cognitive domains were included in the behavioural factors and vice-versa. Furthermore, the only BPSD which impaired continuously with progression of disease severity was apathy which was also the most severe symptom. In conclusion, many cognitive and behavioural syndromes exist in patients with AD. However, the results of this study suggest that cognition and behaviour are independent dimensions.

Are the behavioral symptoms of Alzheimer's disease directly associated with neurodegeneration?

Behavioral and psychological symptoms of dementia (BPSD) are commonly observed over the course of Alzheimers disease (AD). However, it is unclear whether BPSD are part of AD neuropathology or rather represent a psychological reaction to cognitive disabilities. Using voxel-based-morphometry (VBM), we aimed to clarify this issue by investigating patients with AD at different clinical stages. Twenty-seven patients with AD (12 early [ADe] and 15 moderate [ADm]), 19 with amnestic mild cognitive impairment (a-MCI), and 23 healthy controls underwent MRI scanning at 3T. Assessment of BPSD was done in each patient using the Neuropsychiatric Inventory-12 (NPI-12). VBM was used to investigate changes in grey matter (GM) atrophy across groups, and associations between regional GM volumes and occurrence and severity of BPSD in patients. Mood disorders, anxiety, and agitation were present in both a-MCI and AD, while psychotic symptoms were observed mainly in AD. As expected, VBM showed only limited areas of GM atrophy in a-MCI patients, with a progressive extension in ADe and ADm patients (PFWE-corrected-values < 0.05). Disinhibition was strongly associated with GM volume in bilateral cingulate and right middle frontal gyri, while delusions were associated with GM volume in right hippocampus (PFWE-corrected-values < 0.05). This study confirms that BPSD are present since the earliest AD stages. Interesting associations were found in regions traditionally implicated by AD neuropathology. This suggests that BPSD are likely to represent clinical features of AD and should be regarded for their diagnostic and prognostic value.

Hippocampal atrophy is the critical brain change in patients with hypoxic amnesia

Anoxia is considered a good model for studying amnesia. However, not all individuals who experience anoxic events develop memory problems. Moreover, the question still remains about whether, after anoxia, damage is limited to the hippocampus in patients with amnesia and without other significant cognitive deficits. Here we investigated brain damage in a selected sample of adults affected exclusively by an amnesic syndrome after an anoxic episode. The cerebral MR images of these patients were submitted to visual inspection, volumetric measurements of the mesial temporal structures following manual segmentation, and to Voxel‐Based Morphometry of the whole brain. We studied five anoxic patients and thirty‐three well‐matched healthy subjects. Our aim was to: (a) quantify regional atrophic changes associated with chronic anoxic damage compared to control subjects (Group Comparison Analysis); (b) identify regions of common abnormality across all patients (Conjunction Analysis in the VBM); (c) investigate whether measures of regional volume reduction correlated with neuropsychological memory scores; (d) compare the results obtained with visual inspection and ROI analyses with those obtained with VBM. We found that anoxic patients presented a significant reduction of gray matter volume in the hippocampus bilaterally compared to healthy subjects. The only common atrophic region across all patients was the hippocampus bilaterally. Correlation analysis showed only a trend between the Prose immediate free recall test and the left hippocampus. Our findings confirm that the hippocampus is very sensitive to damage stemming from anoxia. Patients with hypoxic amnesia may present damage in other brain regions, but only hippocampal atrophy is common in all of them.

Verbal and spatial memory spans in Alzheimer's and multi-infarct dementia

This study aimed to explore verbal and spatial memory spans in Alzheimers (AD) and multi‐infarct (MID) demented patients. For this purpose, we administered the forward and backward versions of the Digit Span and of the Corsi test to 18 AD, 18 MID and 26 controls. Results revealed a normal forward verbal span but reduced backward verbal and forward and backward spatial spans in both demented groups. These data are discussed in the light of the Working Memory model. It is argued that the normal verbal forward span is sustained by a normally functioning Articulatory Loop. The deficient processing resources of the Central Executive, on the other side, are responsible for the reduced extension of the other memory spans. The possible anatomical substrate of short‐term memory impairment in dementia, as well as alternative interpretations of memory span performance in demented patients are discussed.

Bilateral damage to the mammillo-thalamic tract impairs recollection but not familiarity in the recognition process: a single case investigation

Focal damage confined to the hippocampus may result in recognition deficits characterized by a dissociation between impaired recollection and preserved familiarity. Here, we report a single case of an amnesic patient with bilateral damage to the anterior part of the thalamus, who presented with a neuropsychological profile suggesting such a dissociation. We hypothesized that this focal damage involved the so-called Delay and Brions circuit, which has been theorized to subserve episodic memory processes, but at a different anatomical level than in patients with hippocampal lesions. Using two independent experimental paradigms (remember/know and confidence receiver operating characteristics [ROC]) and recruiting a sex- and age-matched group of healthy controls, we demonstrated that this patients recognition deficits were due to a selective impairment of recollection with a normal familiarity process. The patient underwent an ad hoc brain MRI study, and a quantitative analysis of his MR images was performed. Tissue damage extended bilaterally to the mammillo-thalamic tract, with complete preservation of the medio-dorsal thalamic nuclei. Our findings support the idea that the same functional specialization hypothesized for the different sub-regions of the mesial temporal lobe might also extend to the thalamus. This case will be discussed in light of its implications in support of recent theories, which regard recollection and familiarity as independent processes associated with different neural circuits.

Alzheimer's disease and frontal variant of frontotemporal dementia-- a very brief battery for cognitive and behavioural distinction

AbstractThe aim of this study was to investigate whether a brief neuropsychological battery consisting of a limited number of cognitive tests and an evaluation of the behavioural domains intended to discriminate between frontotemporal dementia (fv–FTD) and Alzheimers disease (AD), constitutes a useful instrument for making a differential clinical diagnosis between these two pathologies. Nineteen fv–FTD and 39 AD patients were compared on cognitive tasks (assessing memory, executive functions, language and constructional praxis) and on the NPI behavioural assessment. A stepwise discriminant analysis was performed to identify the linear combination of cognitive and behavioural measures able to best discriminate between the two groups. One test for each of the investigated cognitive domains (Delayed Prose Recall, FAS verbal fluency, Boston naming test, Reys Figure A Copy) and the four subscales of the Neuropsychiatry Inventory (NPI) which best differentiated between fv–FTD and AD patients (apathy, disinhibition, euphoria, aberrant motor behaviour) were used. The analysis selected Reys Figure A Copy, FAS verbal fluency and NPI apathy subscale as the best discriminants between fv–FTD and AD patients. The final equation assigned 73.7% of the fv–FTD patients and 94.7% of the AD patients to the correct diagnostic group. A validation study conducted on a new independent sample of 11 fv–FTD and 22 AD patients confirmed the high sensitivity (82.6 %) and specificity (81.8%) of the diagnostic equation in assigning fv–FTD and AD patients to the correct dementia group. Although both cognitive and behavioural differences exist between FTD and AD, previous studies have aimed at differentiating the two pathologies by considering the two aspects separately and discriminant analyses were focused only on neuropsychological or neuropsychiatric evaluations. The present results emphasise the importance of rating both cognitive and behavioural clinical features of the two syndromes as objectively as possible to improve differential diagnostic accuracy.