Selective frontal neurodegeneration of the inferior fronto-occipital fasciculus in progressive supranuclear palsy (PSP) demonstrated by diffusion tensor tractography

<p>Abstract</p> <p>Background</p> <p>The clinical presentation in progressive supranuclear palsy (PSP), an atypical parkinsonian disorder, includes varying degrees of frontal dysexecutive symptoms. Using diffusion tensor imaging (DTI) and tractography (DTT), we investigated whether diffusion changes and atrophy of the inferior fronto-occipital fasciculus (IFO) occurs in PSP and if these changes correlate with disease stage and clinical phenotype. The corticospinal tract (CST), which is often involved in PSP, was investigated for comparison.</p> <p>Methods</p> <p>DTI of the whole brain was performed with a 3 T MR scanner using a single shot-EPI sequence with diffusion encoding in 48 directions. Scans were obtained in patients with PSP (n = 13) and healthy age-matched controls (n = 12). DTT of the IFO and CST was performed with the PRIDE fibre tracking tool (Philips Medical System). Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were calculated and correlated with disease stage and clinical phenotype.</p> <p>Results</p> <p>In patients with PSP, significantly decreased FA and increased ADC was found in the frontal part of IFO compared with the medial and occipital parts of IFO, as well as compared to controls. Four of the thirteen patients with PSP showed a marked decrease in the number of tracked voxels in the frontal part of IFO. These findings were most pronounced in patients with severe frontal cognitive symptoms, such as dysexecutive problems, apathy and personality change. There was a strong correlation (r²= -0.84; p < 0,001) between disease stage and FA and ADC values in the CST.</p> <p>Conclusions</p> <p>DTT for identification of neuronal tracts with subsequent measurement of FA and ADC is a useful diagnostic tool for demonstrating patterns of neuronal tract involvement in neurodegenerative disease. In selected tracts, FA and ADC values might act as surrogate markers for disease stage.</p

Aspects of Frontal and Medial Temporal Brain Functions : Neuropsychological and functional imaging studies in normals and in frontotemporal dementia

The thesis is based on five investigations. In the first study the nature and the degree of cognitive impairment of patients with frontotemporal dementia (FTD) is explored. The results from neuropsychological assessment are described as three levels of cognitive impairment. These levels of functional disturbance corresponded to increased severity of abnormality of the regional cerebral blood flow measurements (rCBF). In the second study a close coupling between reduced rCBF and specific neuropsychological deficits in FTD is demonstrated. Significant correlations were found between a global impairment score and relative blood flow in frontal areas. The global impairment scale might be useful in detecting and following the progress of frontal deficiencies in FTD patients. The results of the third investigation indicate that for differential diagnosis of FTD versus dementia of Alzheimer type (DAT) the scores on cognitive tests measuring verbal ability, visuospatial ability and verbal episodic memory are of value, especially when evaluated in combination. The fourth study investigates the functional involvement of the frontal lobes during performance of verbal (VFT) and design fluency tasks (DFT), and the influence of different strategies utilised when solving the fluency tasks. The results from measurements of rCBF in normal subjects demonstrate a left-sided frontal activation during the VFT and bilateral flow augmentations during the DFT. Furthermore, the findings suggest that patterns of cortical activity vary according to the chosen cognitive strategy when performing a task. In the fifth investigation the involvement of the medial temporal lobes (MTL) in retrieval of declarative memories (abstract visuospatial designs) is studied by measuring rCBF with positron emission tomography (PET). In the recall of abstract designs a less practised memory state (novel recall) was compared to a well practised (trained recall) memory state. The MTL was more activated during retrieval in the less practised memory state compared to the well practised memory state, indicating a changing role of the MTL during recall in the earlier stages of acquisition of declarative knowledge compared to the well encoded declarative memory state

Subjective memory complaints, neuropsychological performance and psychiatric variables in memory clinic attendees: A 3-year follow-up study.

The aims were to evaluate the cognitive performance and clinical diagnosis in patients (<75 years) seeking help for subjective memory complaints, to determine the prevalence of certain psychiatric symptoms and to conduct follow-up examinations. At baseline 41% showed normal cognitive performance (subjective memory impairment; SMI), 37% fulfilled criteria for mild cognitive impairment (MCI) and 22% were classified as dementia. There were significant associations between the three groups and experiences of psychosocial stress and feelings of anxiety. The proportion of psychosocial stress was significantly higher in SMI vs. MCI and SMI vs. dementia. Feelings of anxiety were significantly higher in SMI vs. MCI. At the 3-year follow-up, 88% of the SMI patients remained stable SMI and 60% of the MCI patients remained stable. There was a significant reduction of psychosocial stress and moderate reduction of feelings of anxiety among the SMI patients. The findings indicate that the risk of patients with SMI developing dementia is small within a 3-year span. We propose that subjective memory complaints might be influenced by the presence of psychosocial stress and feelings of anxiety disturbing the memory processes and interfering with the patients' evaluation of their memory function

Stability in the clinical characteristics of patients with memory complaints.

The objectives of this study were to examine potential clinical and neuropsychological changes over time in non-demented patients with subjective memory complaints (</=70 years) and to compare the patients with objective memory impairment (OMI) with those who suffer from subjective memory impairment (SMI). OMI and SMI patients did not differ regarding duration of memory problems, age or education. At baseline no differences were revealed between the OMI and SMI patients regarding self-reported cognitive deficits, self-reported worry about deficits, and symptoms of anxiety or depression. None of the patients had converted to dementia at follow-up. Eighty percent of the OMI patients and 61% of the SMI patients reported cognitive deficits to the same degree at follow-up as at baseline. Despite a significant reduction of depressive symptoms in the OMI patients, a considerable portion of both OMI and SMI patients scored above the cut off score on both anxiety and depression subscales at baseline as well as at follow-up. Our study reveals close points of similarity between patients with memory complaints, verified by test, and patients with memory complaints, not verified by test, as well as stability over time regarding important clinical aspects

Frontotemporal dementia – Differentiation from Alzheimer's disease

Organic dementia is dominated by primary degenerative disorders such as Alzheimer’s disease (AD) and frontotemporal dementia (FTD). FTD is a distinct clinical syndrome with behavioural, personality, emotional and language disturbances preceding the cognitive decline. This clinical presentation is distinctly different from that of AD which is characterized by early cognitive changes, such as memory impairment, aphasia and apraxia, and a relatively preserved personality and behaviour. The differences between these two conditions reflect the predominant topographic distribution of brain pathology. The differences in clinical profiles and treatment strategies will be highlighted. In both disorders loss of functional ability, development of behavioural disturbances and dependency impose heavy demands on family and other caregivers. This presentation will concentrate on early recognition and diagnosis, using systematic clinical evaluation, neuropsychological testing and different brain imaging methods. This is important for a successful development of therapeutic strategies for both cognitive and behavioural symptoms in FTD and AD

99mTC-HMPAO-SPECT related to clinical findings in patients with subjective experience of memory deficit

Objective. The aim was to evaluate cognitive impairments, psychiatric symptoms and cerebral blood flow (CBF) patterns in middle-aged and younger old patients with subjective experience of memory deficits. Methods. The CBF was measured by 99m-Tc-HMPAO-SPECT. The study group was heterogeneous with patients fulfilling criteria for dementia (n=13) and patients with mild cognitive impairment (MCI; n= 24) as well as with not verified cognitive impairment (Non-MCI; n=17). The MCI patients were subdivided into two groups. The MCI type 1 group (n=14) had isolated memory impairments while the MCI type 2 group (n=10) had memory impairments together with slight verbal and/or visuospatial disturbances. Results. The MCI type 1 group showed lower blood flow in the left middle/inferior gyrus and in parts of the left inferior parietal lobe compared to the Non-MCI group. The MCI type 2 group showed reductions in the left anterior medial temporal lobe as well as in parts of the posterior cingulate gyrus. The Non-MCI patients reported high incidence (70%) of long-lasting psychosocial stress. Conclusions. The combination of clinical and CBF data provides diagnostically meaningful information about regional brain dysfunction in patients with memory deficits

Instruction-specific brain activations during episodic encoding: a generalized level of processing effect

In a within-subject design we investigated the levels-of-processing (LOP) effect using visual material in a behavioral and a corresponding PET study. In the behavioral study we characterize a generalized LOP effect, using pleasantness and graphical quality judgments in the encoding situation, with two types of visual material, figurative and nonfigurative line drawings. In the PET study we investigate the related pattern of brain activations along these two dimensions. The behavioral results indicate that instruction and material contribute independently to the level of recognition performance. Therefore the LOP effect appears to stem both from the relative relevance of the stimuli (encoding opportunity) and an altered processing of stimuli brought about by the explicit instruction (encoding mode). In the PET study, encoding of visual material under the pleasantness (deep) instruction yielded left lateralized frontoparietal and anterior temporal activations while surface-based perceptually oriented processing (shallow instruction) yielded right lateralized frontoparietal, posterior temporal, and occipitotemporal activations. The result that deep encoding was related to the left prefrontal cortex while shallow encoding was related to the right prefrontal cortex, holding the material constant, is not consistent with the HERA model. In addition, we suggest that the anterior medial superior frontal region is related to aspects of self-referential semantic processing and that the inferior parts of the anterior cingulate as well as the medial orbitofrontal cortex is related to affective processing, in this case pleasantness evaluation of the stimuli regardless of explicit semantic content. Finally, the left medial temporal lobe appears more actively engaged by elaborate meaning-based processing and the complex response pattern observed in different subregions of the MTL lends support to the suggestion that this region is functionally segregated

Psychiatric Symptoms and Their Psychosocial Consequences in Frontotemporal Dementia.

Based on a retrospective study of 19 neuropathologically verified cases with frontotemporal dementia (FTD), neuropsychiatric symptoms related to behavioral disturbances and their psychosocial consequences were studied. The results indicate that frontotemporal dementia is often misdiagnosed early in the clinical course. Behavioural features with impaired social interactions, impaired personal regulation, and loss of insight were seen in all patients. The psychosocial consequences reported in this paper challenge future research in frontotemporal dementia