Thomas H. Bak

The differentiation of semantic dementia and frontal lobe dementia (temporal and frontal variants of frontotemporal dementia) from early Alzheimer's disease: A comparative neuropsychological study.

The authors compared age-matched groups of patients with the frontal and temporal lobe variants of frontotemporal dementia (FTD; dementia of frontal type [DFT] and semantic dementia), early Alzheimers disease (AD), and normal controls (n = 9 per group) on a comprehensive neuropsychological battery. A distinct profile emerged for each group: Those with AD showed a severe deficit in episodic memory with more subtle, but significant, impairments in semantic memory and visuospatial skills; patients with semantic dementia showed the previously documented picture of isolated, but profound, semantic memory breakdown with anomia and surface dyslexia but were indistinguishable from the AD group on a test of story recall; and the DFT group were the least impaired and showed mild deficits in episodic memory and verbal fluency but normal semantic memory. The frontal and temporal presentations of FTD are clearly separable from each other and from early AD.

The effects of motor neurone disease on language: further evidence.

It might sound surprising that Motor Neurone Disease (MND), regarded still by many as the very example of a neurodegenerative disease affecting selectively the motor system and sparing the sensory functions as well as cognition, can have a significant influence on language. In this article we hope to demonstrate that language dysfunction is not only a pronounced and well documented symptom in some MND patients but also that the study of language in MND can address interesting theoretical questions about the representation of language and conceptual knowledge in the brain. After a brief introduction delineating clinical and pathological features of the disease we discuss the evidence available in the literature for language dysfunction in MND. We then present linguistic data from our own study of seven patients with MND/dementia/aphasia syndrome focusing on the dissociation between noun and verb processing. To illustrate the clinical, neuropsychological and linguistic aspects of MND we describe in more detail the patient E.N., a pathologically confirmed case of MND/dementia. Finally, we attempt to characterise the nature of the linguistic impairment in MND in the light of current debates about the mechanisms underlying noun/verb dissociation.

Subcortical dementia revisited: Similarities and differences in cognitive function between progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and multiple system atrophy (MSA)

To examine the similarities and differences in cognitive function between three predominantly subcortical dementing disorders associated with parkinsonism we compared the profiles of cognitive performance in 39 patients with Progressive Supranuclear Palsy (PSP), 26 patients with Multiple System Atrophy (MSA) and 25 with Corticobasal Degeneration (CBD) with those of 30 patients with classic cortical dementia, Alzheimer’s Disease (AD), using two different cognitive screening tests: Dementia Rating Scale (DRS) and Addenbrooke’s Cognitive Examination (ACE). The cognitive profile on ACE and DRS subtests distinguished subcortical diseases from each other as well as from AD. All parkinsonian syndromes were characterized by a disproportionate impairment in verbal fluency, particularly letter fluency. The three diseases differed, however, in the degree of language, memory and visuospatial impairment. We conclude that similarities, as well as differences, between PSP, MSA and CBD can be detected using a brief, clinically applicable cognitive screening test. The pattern of cognitive impairment is likely to reflect a different distribution of pathology, in particular a higher degree of cortical involvement in PSP and CBD. We would like to thank Marion Wilkinson and Ashley Muir for their help in preparation of the manuscript, Joanna Drake and Tina Emery for their assistance in testing patients and controls and Sharon Davies for her assistance in data management. Our work on PSP and CBD patients has been generously supported by the PSP Association, our work on MSA patients by Sarah Mathieson Trust.

Corticobasal degeneration as a cognitive disorder

The presence of cognitive impairment in corticobasal degeneration (CBD) is now widely recognised. Our review of the literature reveals that, although the pattern and severity of neuropsychological impairments can be highly variable across patients, several general trends can be identified. The most characteristic impairments are limb apraxia (usually ideomotor), constructional and visuospatial difficulties, acalculia, frontal dysfunction, and nonfluent aphasia. The limb apraxia is associated with deficits in drawing, copying, and handwriting, but there is emerging evidence that the problems with handwriting are not due exclusively to the apraxia. The findings with respect to episodic memory are more variable, but when there is impairment in this area, it tends to be milder than that seen in Alzheimers disease. Semantic memory functioning appears relatively preserved but has been poorly studied. Problems with speech are common, and may be due to dysarthria or buccofacial apraxia. Aphasia, although initially considered rare, is in fact a common accompaniment of CBD, may be the presenting feature, and is typically nonfluent in type. More systematic investigation of the clinical and neuropathological overlap between progressive nonfluent aphasia (generally considered to be a form of frontotemporal dementia) and CBD is needed.© 2003 Movement Disorder Society

Motor neurone disease, dementia and aphasia: coincidence, co-occurrence or continuum?

Abstract Cognitive, and particularly aphasic, symptoms associated with motor neurone disease (MND) are still frequently described as rare and “recently discovered”. This review demonstrates that the association between MND and dementia was described and recognised as an entity as early as 1929, and its close relationship to Picks disease was postulated in 1932. Changes in language production and comprehension were also observed by early authors, although they were rarely described as aphasia. The striking similarity to the contemporary descriptions is, however, sometimes obscured by diverging terminology. The syndromes of MND/dementia and MND/aphasia are well established but represent a comparatively small subgroup of MND. In addition, subtle cognitive alterations have also been reported in non-demented MND patients; most studies have found evidence of frontal-executive dysfunction, similar in pattern, but much milder than in patients with frank MND/dementia. These findings are strengthened further by post-mortem studies demonstrating pathological changes in the frontal lobes, and functional neuroimaging studies, showing reduced frontal activation. The issue of whether memory, visuospatial skills and language are affected in non-demented subjects remains, however, controversial. Further studies are required to establish whether MND/dementia and MND/aphasia form separate disease entities or can be viewed as extreme forms of a cognitive deficit characteristic of MND in general.

Apraxia, mechanical problem solving and semantic knowledge: contributions to object usage in corticobasal degeneration

Abstract To investigate the nature of the apraxia in corticobasal degeneration (CBD) five patients with CBD and five matched controls were compared on tests of: i) meaningless and symbolic gesture production, ii) a battery of semantic tasks based on 20 everyday items (involving naming and picture-picture matching according to semantic attributes, matching gestures-to-objects, object usage from name and with the real object) and iii) a novel tool test of mechanical problem solving.All five patients showed severe impairment in the production of meaningless and symbolic gestures from command, and by imitation, and were also impaired when using real objects. Deficits were not, however, restricted to action production: four were unable to match gestures to objects and all five showed impairment in the selection and usage of novel tools in the mechanical problem solving task. Surprising was the finding of an additional semantic knowledge breakdown in three cases, two of whom were markedly anomic. The apraxia in CBD is, therefore, multifactorial. There is profound breakdown in the organisation and co-ordination of motor programming. In addition, patients show central deficits in action knowledge and mechanical problem solving, which has been linked to parietal lobe pathology. General semantic memory may also be affected in CBD in some cases and this may then contribute to impaired object usage. This combination of more than one deficit relevant for object use may explain why CBD patients are far more disabled by their dyspraxia in everyday life than any other patient group.

Naming and comprehension in primary progressive aphasia: The influence of grammatical word class

Background: Various clinical types of primary progressive aphasia have been associated with distinct areas of atrophy and pathological changes. Therefore, differences in the patterns of language deterioration in the various types might reveal the types of language processes and representations that depend on the areas of brain that are disproportionately affected. Aims: To test the hypotheses (1) that individuals with progressive nonfluent aphasia (associated with left posterior, inferior frontal, and insular atrophy) show progressive motor speech impairment and disproportionate deterioration in naming actions relative to objects, and (2) that individuals with semantic dementia (associated with anterior and inferior temporal atrophy) show disproportionate deterioration in semantic representations of objects relative to actions. Methods & Procedures: The study population consisted of 56 participants with primary progressive aphasia, including 27 with progressive nonfluent aphasia, 16 with semantic dementia, and 13 with amyotrophic lateral sclerosis‐frontotemporal dementia (ALS‐FTD). Participants were given tests of oral and written naming and tests of picture and word association with object and action stimuli. Differences across tests within each group were evaluated. Associations between motor speech impairment (based on a clinical motor speech examination) and naming impairment in each grammatical word class were evaluated. Outcomes & Results: Participants with progressive nonfluent aphasia and ALS‐FTD showed significantly more impairment in naming actions than objects. In contrast, participants with semantic dementia were significantly more impaired in naming objects than actions, and more impaired on semantic tests of objects relative to actions. In all groups, all participants who were more impaired in naming actions also had impaired motor speech (dysarthria and/or apraxia of speech). Conclusions: Distinct patterns of deterioration across grammatical word classes in these clinical subtypes were documented. Together with evidence that these clinical subtypes are associated with different areas of brain atrophy in other studies, our results are consistent with a role of posterior inferior frontal cortex and insula in motor speech and naming actions, as well as the essential role of anterior temporal lobes in semantic representation of objects.

Ubiquitin-positive inclusions and progression of pathology in frontotemporal dementia and motor neurone disease identifies a group with mainly early pathology

Frontotemporal lobar degeneration (FTLD) with tau‐negative, ubiquitin‐positive inclusions has been a topic of major interest in recent years, with this group now accounting for the majority of tau‐negative cases of frontotemporal degeneration. The severity of neurodegeneration in FTLD is dependent on the stage of disease and is substantial even in the earliest stages. Elucidating the pathogenesis of FTLD requires evaluation of changes during the earliest possible stage of disease. However, the long survival of most frontotemporal dementia cases means that cases with early neuropathology are not frequently encountered. Cases of FTLD with the shortest survival are those with coexisting motor neurone disease (FTLDu2003+u2003MND), making these the ideal group for studying early FTLD pathology. It is not clear, however, what the pathological contribution of MND is in these cases. This study evaluates the pathology of 20 cases of FTLD (11 with no clinical signs of MND and nine with FTLDu2003+u2003MND) as well as 10 cases of MND without dementia. Our findings indicate that the deposition of ubiquitin does not play a key role in the neurodegenerative process in FTLD, and that the severity of neurodegeneration in FTLD is similar in cases with and without clinical MND.

International medical workshop covering progressive supranuclear palsy, Multiple System Atrophy and cortico basal degeneration

The PSP Association was registered as a charity in the United Kingdom by Sara and Michael Koe, after the former was diagnosed as having this disease. Sara sadly died from it in January, 1995. The three main objectives of the PSP Association are to promote research into PSP worldwide, provide information and support for patients and caregivers, and engender awareness of the disease and the Association, across Europe. The Association has come a long way in the last five years. Its achievements have included: (1) sponsoring a research fellow at the National Hospital for Neurology in 1996/7 to collate all existing research on PSP worldwide; (2) the part-funding of a Research Fellow in Cambridge from 1997 to look into the neuro-psychological, neuro-psychiatric, and behavioral effects of PSP on patients; (3) the holding of annual symposia for caregivers and therapists; (4) the establishment of a telephone counseling service for patients and caregivers; (5) setting up of numerous PSP support groups across the UK; (6) funding a PSP Association clinical research fellow at the Institute of Neurology, Queen Square, London, seeking to identify susceptibility genes to PSP; (7) sponsoring a research fellow from 1999 to carry out a concentric epidemiological study of PSP, based in Newcastle, in which the inner circle is the city itself, looked at in great detail; with a middle ring covering a population of some 3.5 million in the North of England in less detail, and an outer ring covering the whole UK, and, finally, (8) sponsoring in the UK in 1996 the first ever International Medical Workshop to be held with a specific focus on PSP; and this second workshop, which was held at Stowe School in September 1999. Corticobasal degeneration is particularly closely related to PSP and, in the eyes of some neurologists, is the same disease. There is no supporting society. However, the PSP Association and, to an extent, the Parkinson’s Disease Society, act as an umbrella organization to take in and support CBD patients.