Frontotemporal dementia, semantic dementia, and Alzheimer's disease: the contribution of standard neuropsychological tests to differential diagnosis

CERAD-NAB (Consortium to Establish a Registry for Alzheimer's Disease-Neuropsychological Assessment Battery) data were compared between 51 patients with frontotemporal dementia, 13 with semantic dementia, and 69 with Alzheimer's disease. There were statistically significant differences between the 3 groups. Compared with patients with Alzheimer's disease, patients with frontotemporal dementia were more impaired on Animal Fluency but not on any other CERAD-NAB subtest. Patients with semantic dementia performed worse in Animal Fluency and Boston Naming Test compared with frontotemporal dementia and Alzheimer's disease. Multiple logistic regression analysis revealed that in the differentiation between frontotemporal dementia and Alzheimer's disease, the combination of Animal Fluency and Boston Naming Test correctly classified 90.5% of patients. In segregating semantic dementia and Alzheimer's disease, the combination of Boston Naming Test and Mini Mental State Examination resulted in a correct classification of 96.3%. These findings demonstrate that the Mini Mental State Examination and the language subtests of the CERAD-NAB are valuable clinical instruments for the differential diagnosis between early frontotemporal dementia, semantic dementia, and Alzheimer's disease.     

Clinical features of pathologic subtypes of behavioral--variant frontotemporal dementia

OBJECTIVE: To identify clinical features in behavioral-variant frontotemporal dementia that may help predict tau-positive pathology. METHODS: Clinical and historical features of patients with pathologically confirmed tau-positive and tau-negative frontotemporal lobar degeneration from 1970 to 2006 were retrospectively reviewed in a blinded fashion. The initial clinical features of those patients who eventually met consensus criteria for frontotemporal dementia were examined using univariate and cluster analyses to explore characteristics that may be associated with tau pathology. RESULTS: Fifty-six patients (24 tau-positive cases) were included in the analysis. There was no difference in demographics between the tau-positive and tau-negative cases. Univariate analysis showed that poor planning and/or judgment was more commonly associated with tau-positive pathology (P = .03). Cluster analysis using behavioral characteristics identified 2 groups of patients: cluster 1 contained mainly tau-positive cases (57%) and cluster 2 was mostly tau-negative cases (71%). Poor planning and/or judgment was a common presenting sign in the first group (P < .001), while the second group was more likely to present with impaired regulation of personal conduct (P < .001) and a decline in personal hygiene (P = .005). CONCLUSIONS: Poor planning and/or judgment was associated with behavioral-variant frontotemporal dementia patients who had tau-positive pathology. The constellation of impaired personal conduct and a paucity of dysexecutive symptoms identified tau-negative patients.     

Diagnostic criteria for fronto-temporal lobe degeneration

Circumscribed atrophy of the frontal and temporal lobes (frontotemporal lobar degeneration) accounts for about one fifth of cases of primary degenerative dementia occurring before the age of 65. It produces three prototypical clinical syndromes. The most common is frontotemporal dementia, characterized by personality change and profound alteration in social conduct and associated with bilateral atrophy of the frontal and anterior temporal lobes. Progressive non-fluent aphasia is characterized by difficulty in verbal expression, anomia and phonemic errors in the presence of relative preservation of comprehension and associated with atrophy predominantly of the left hemisphere. In semantic dementia there is fluent speech with semantic errors and severely impaired comprehension and naming, together with a visual associative agnosia, resulting from bilateral atrophy of the inferior and middle temporal gyri. The clinical syndromes occur with either of two main histological types: prominent microvacuolar change, without specific histological features (frontal lobe degeneration-type), severe astrocytic gliosis with or without ballooned cells and inclusion bodies (Pick-type). To improve clinical recognition and advance understanding of this relatively common form of cerebral degeneration, members of an international workshop on Frontotemporal Lobar Degeneration developed consensus criteria, building upon earlier published clinical diagnostic guidelines for frontotemporal dementia. The consensus criteria reported here specify core and supportive features for each of the prototypical clinical syndromes: frontotemporal dementia, progressive aphasia and semantic dementia, as well as providing broad inclusion and exclusion criteria for the generic entity of frontotemporal lobar degeneration.     

The situation of caregiver counselling in patients with frontotemporal lobar dementia in old psychiatry

Caregiver counselling is an indispensable feature of current concepts for dementia treatment. Self-support groups and psychoeducative programms for caregivers of patients with Alzheimer's disease may reduce the burden of nursing and psychological strain. Specific caregiver needs from patients with frontotemporal lobar dementia (FTLD [frontotemporal dementia, semantic dementia, progressive aphasia, corticobasal degeneration]) are only partially taken into account. We conducted a German wide epidemiologic study which revealed that specific counselling for supporting relatives and caregivers of patients with FTLD is only fragmentary in hospital services for old age psychiatry. In most cases, they are referred to the local Alzheimer's disease Associations (89 %). Besides that, the existence of large hospital care units has significant negative repercussions on psychosocial supply for caregivers of patients with FTLD. To establish decentralized support units by these hospitals would lead to a significant improvement of medical and social care in this field.     

Aggression in the elderly

Aggression is a common behavioral symptom of dementia. Aggression is associated with frontotemporal dementia, greater dementia severity, cognitive decline, and other behavioral and psychological disturbances. It is influenced by the environment and has been correlated with neuropathologic changes and certain polymorphisms. Aggression in dementia patients results in higher psychotropic use and distress to family caregivers and nursing home staff; it is predictive of institutionalization. There is empirical evidence for the efficacy of pharmacotherapy and more limited evidence for psychosocial interventions in the successful management of aggression in persons with dementia. Management of aggression should include comprehensive assessment of medical, psychological, and environmental variables.     

Frontotemporal dementia and frontotemporal degeneration--how to define?]

The term of the frontotemporal dementia was first proposed by Lund and Manchester group in 1994, but the definition of frontotemporal dementia has been still controversial. Frontotemporal dementia is caused by several diseases which have fronto-temporal atrophy. The diseases are collectedly designated as frontotempoal degeneration. The frontotemporal degeneration encompasses several diseases such as Pick disease (frontotemporal degeneration with Pick bodies) and frontotemporal degeneration with ubiquitin-positive inclusions and frontotemporal degeneration (no inclusion bodies are observed). Pick bodies are consisted of abnormally phosphorylated tau protein. The recent discoveries of tau mutations in frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) suggest important role of tau abnormalities in the disease mechanism. The frontotemporal degeneration has also another clinical phenotype such as slowly progressive aphasia. Slowly progressive aphasia has subtypes of non-fluent aphasia and semantic aphasia. Some patients with corticobasal degeneration or progressive supranuclear palsy also reveal the clinical pictures of frontotemporal dementia or slowly progressive aphasia and should be considered as differential diagnosis in the patients with frontotemporal dementia or slowy progressive aphasia.     

A brief neuropsychological assessment for the differential diagnosis between frontotemporal dementia and Alzheimer''s disease

The neuropsychological performance (including measures of language, semantic memory, visual and spatial perception and executive functions) of a group of 14 patients with the clinical diagnosis of probable frontotemporal dementia was compared with that of a group of 14 patients with a clinical diagnosis of probable Alzheimer's disease. The aim was to identify a specific cognitive profile of frontotemporal dementia, which could be used to select a sensitive, short evaluation for the differential diagnosis with Alzheimer's disease. Both groups were severely impaired in most tasks, including those 'frontal lobe' tests which have been suggested to play an important role in differential diagnosis. Significant differences were found only for a minority of tests (oral praxis, visual-spatial perception, and verbal fluency). A logistic regression showed that a shortened testing procedure based on four tests (Rey-Osterreith complex figure test recall, phonemic fluency, oral apraxia, and cube analysis) achieved a 70% sensitivity and 80% specificity for the correct classification of patients in the frontotemporal dementia or Alzheimer's disease group. In conclusion, a brief neuropsychological evaluation including these four tests, as well as other measures sensitive to the frontal impairment, can be useful in the differential diagnosis between the two pathologies, along with the clinical data.     

Pain processing in dementia and its relation to neuropathology

Most clinical studies of pain in dementia have focused on assessment procedures that are sensitive to pain in "demented" or "cognitively impaired" elderly patients. The neuropathology of dementia has not played a major part in pain assessment. In this review, the neuropathological effects of dementia on the medial and the lateral pain systems are discussed. We focus on Alzheimer's disease (AD), vascular dementia, and frontotemporal dementia. Lewy-body disease and Creutzfeldt-Jakob disease are briefly reviewed. The results of the studies reviewed show that, although the subtypes of dementia show common neuropathological features (such as atrophy and white-matter lesions), the degree by which they occur and affect pain-related areas determine the pattern of changes in pain experience. More specifically, in AD and even more so in frontotemporal dementia, a decrease in the motivational and affective components of pain is generally present whereas vascular dementia might be characterised by an increase in affective pain experience. Future studies should combine data from experimental pain studies and neuropathological information for pain assessment in dementia.     

Neuropsychiatric symptoms in behavioral variant frontotemporal dementia and primary progressive aphasia

Neuropsychiatric symptoms are well defined in behavioral variant frontotemporal dementia but are not as well studied in primary progressive aphasia. This study compared caregiver reported neuropsychiatric symptoms in these 2 forms of dementia at short and long disease duration. Patients with behavioral variant frontotemporal dementia had more symptoms than patients with primary progressive aphasia. However, when divided by duration of disease, patients with primary progressive aphasia with long duration had a similar number of symptoms to patients with behavioral variant frontotemporal dementia at either duration. Furthermore, this group of patients with primary progressive aphasia had more symptoms typical of behavioral variant frontotemporal dementia and less mood-related symptoms which were more common in patients with primary progressive aphasia with shorter duration. This study illustrates the emergence of neuropsychiatric symptoms as primary progressive aphasia progresses and highlights the increasing overlap with behavioral variant frontotemporal dementia because the disease affects areas outside of the language network.     

Brain atrophy in frontotemporal dementia.

OBJECTIVES--To evaluate the pattern of regional brain atrophy in patients with frontotemporal dementia by comparing it with that in patients with Alzheimer's disease and normal controls. METHODS--Fourteen patients with frontotemporal dementia, 13 with moderate, and 33 with mild Alzheimer's disease, and 31 controls were studied. Atrophy was evaluated with linear measures in the anterior brain, medial temporal lobe, and hippocampal formation regions using MRI. RESULTS--Patients with frontotemporal dementia had greater atrophy in the anterior brain regions than patients with Alzheimer's disease or controls. Atrophy of the hippocampal formation, which best discriminates Alzheimer's disease from controls, was present also in patients with frontotemporal dementia. By contrast, atrophy of the medial temporal lobe, which is also present in Alzheimer's disease, was absent in frontotemporal dementia. CONCLUSION--A pattern of atrophy in the frontal lobes and hippocampal formation with sparing of the medial temporal lobe might be distinctive of frontotemporal dementia. Hippocampal involvement might not be specific for Alzheimer's disease and specific patterns of atrophy might be distinctive of some forms of degenerative dementia.     

A review of the literature on neuroimaging of serotoninergic function in Alzheimer’s disease and related disorders

Summary Behavioural and psychological disorders are frequent not only in frontotemporal dementia (FTD), but also in Alzheimer’s disease (AD), and many of them are related to serotoninergic dysfunction. In vitro biochemical measurements on brain samples show both pre- and post-synaptic impaired brain serotoninergic function in degenerative dementia, sometimes related to hyperactivity or aggressive behaviour. To date, few studies have explored in vivo 5HT2A and 5HT1A brain receptors in AD and FTD. They suggest that brain cells are lost in the associative cortices (5HT2A) and hippocampus (5HT1A) of AD patients, and in the medial prefrontal and orbitofrontal cortices of FTD subjects (5HT2A). Apart from reflecting a loss of local neurons, the meaning of the decrease in 5HT receptors is not yet clear and larger populations are required to establish relationships with clinical symptoms such as dementia severity and search for possible consequences for patients’ behavioural and affective status.     

Face and emotion processing in frontal variant frontotemporal dementia.

Lavenu et al. [Alzheimer Dis. Assoc. Disorder 5 (1999) 96] have shown that patients with frontotemporal dementia (FTD) show impaired recognition of facial expressions. It is not clear, however, whether these deficits arise from an impairment affecting face processing generally, emotion processing generally, or facial expression recognition alone. We address this issue by testing six patients with frontal variant frontotemporal dementia (fvFTD) on a series of face perception tasks (including facial identity and facial expression recognition), and a test of vocal emotion recognition. In general, the fvFTD participants showed impaired recognition of facial expressions in the context of preserved recognition of facial identity. In addition, however, deficits were also observed for the vocal emotion recognition task. These results are consistent with the idea that fvFTD affects the recognition of emotional signals from multiple modalities rather than facial expression processing alone. It is plausible that the emotion recognition impairments observed contribute to the abnormal social behaviour that is characteristic of this condition.     

Prevalence and predictors of neuropsychiatric symptoms in cognitively impaired nursing home patients

The prevalence of neuropsychiatric symptoms and the influence of predictive factors in cognitively impaired nursing home patients were reviewed. Articles were identified by means of a MEDLINE and PsychInfo literature search. Neuropsychiatric symptoms were present in more than 80% of the cognitively impaired patients. Prevalences ranged considerably, from 3% to 54% for delusions, 1% to 39% for hallucinations, 8% to 74% for depressed mood, 7% to 69% for anxiety, 17% to 84% for apathy, 48% to 82% for aggression or agitation, and 11% to 44% for physical aggression. Neuropsychiatric symptoms seemed to be predicted not only by dementia type or stage but also by the psychosocial environment and the amount of psychoactive medication and physical restraints used. Neuropsychiatric symptoms are common and influenced by both the disease itself and the psychosocial environment of the institutional setting. The latter may have important consequences for staff planning and education and the future design of care facilities.     

Frontotemporal dementia in a brazilian kindred with the c9orf72 mutation

OBJECTIVES To describe the clinical features of a Brazilian kindred with C9orf72 frontotemporal dementia-amyotrophic lateral sclerosis and compare them with other described families with C9orf72 and frontotemporal dementia-amyotrophic lateral sclerosis-causing mutations. DESIGN Report of a kindred. SETTING Dementia center at a university hospital. PATIENTS One kindred encompassing 3 generations. RESULTS The presence of a hexanucleotide (GGGGCC) expansion in C9orf72 was confirmed by repeat-primed polymerase chain reaction and Southern blot. The observed phenotypes were behavioral variant frontotemporal dementia and amyotrophic lateral sclerosis with dementia, with significant variability in age at onset and duration of disease. Parkinsonian features with focal dystonia, visual hallucinations, and more posterior atrophy on neuroimaging than is typical for frontotemporal dementia were seen. CONCLUSIONS Behavioral variant frontotemporal dementia due to C9orf72 expansion displays some phenotypic heterogeneity and may be associated with hallucinations, parkinsonism, focal dystonia, and posterior brain atrophy. Personality changes may precede the diagnosis of dementia by many years and may be a distinguishing feature of this mutation.     

Syndrome démentiel dans les suites d’une bipolarité

Introduction

Converging evidence suggests that people with bipolar disorder (BPD) exhibit persistent cognitive impairment independently from the emotional state. In old age BPD, the cognitive decline is more severe and can fulfill the criteria of dementia. However, the characteristics of bipolar disorder dementia are still unknown.

Aim of the study

The aim of the study was to characterise the cognitive and imaging profile of the dementia following bipolar disorder.

Method

Patients fulfilling criteria of dementia and followed-up in the memory unit for at least two years were included. Patients with substance abuse were excluded. A battery of specific (assessing verbal memory, attention, frontal executive function, construction and visuospatial impairment), and global (MMSE and Mattis dementia rating scale) neuropsychological tests, behavioural assessment using the frontotemporal behavioural scale, MRI and HMPAO–SPECT imaging were performed in all patients during euthymic state.

Results

We included 13 patients with bipolar disorder (9W/4M). The mean age was 70.8 years (±7.7). Dementia began in average 29.2 years (±10.1) after the onset of the bipolar disorder. The mean score of MMSE was 24.0 (±4.3). The mean score of the Mattis dementia rating scale was 122.5 (±8.9). After an average of 6.1 years (±2.8) of follow-up, the mean score of MMSE was 23.5 (±3.2). The annual MMSE score decrease was of 0.5 (±4.4) per year. In more than 75% of the patients, Trail-Making Test-part B, Go-nogo test, Stroop test, delayed free recall in verbal explicit long-term memory test, category fluency tasks and code test were impaired. In more than 50% of patients, free recall, delayed cued recall, clock test, visuospatial battery and temporal orientation were impaired. On the other hand, spatial orientation and recognition were within the standards. The mean of the BREF score was 10.6 (±3.2). A moderate frontal behavioural syndrome was observed, but never persistent hallucinations. Seven patients had been treated with lithium and seven with antipsychotics, but none during the neurological assessment. Moderate extrapyramidal signs were reported in 10 patients, of which the seven patients treated in the past with antipsychotics. MRI showed no focal atrophy and no vascular lesions. Functional imaging conducted in 10 patients always showed uptake decrease in the frontotemporal regions and sometimes in the parietal region too. After six years of follow-up, no patient fulfilled the probable criteria for the main dementia, Alzheimer disease, vascular dementia, frontotemporal dementia and dementia with Lewy bodies.

Conclusion

The data of this study support a possible specific dementia postbipolar disorder and not only mild cognitive decline. This hypothesis could be tested in a prospective study. Such dementia could be a main differential diagnosis from long lasting frontotemporal dementia. The pathogenic process of this dementia could also be determined.     

A juvenile case of frontotemporal dementia: Neurochemical and neuropathological investigations

1. 1. An autopsy case of frontotemporal dementia with onset at the early age of 28 years is reported.

2. 2. The neuropathological features consisted of limited, knife-like frontotemporal atrophy with severe neuronal loss, spongiform change and gliosis, which is compatible with the frontotemporal dementia.

3. 3. Biochemical determinations disclosed that biogenic amines and their metabolites, predominant in the dopaminergic markers, were depleted in the damaged regions.

4. 4. Since biochemical data in frontotemporal dementia are few in previous studies, it, will be determined whether these biochemical changes are characteristic for the juvenile type of f rontotemporal dementia or not.

     

TAU mutations are not a predominant cause of frontotemporal dementia in Canadian patients

OBJECTIVE: Frontotemporal dementia is a neurodegenerative disease affecting mostly the frontal and/or temporal lobes, with neuronal loss and intraneuronal and/or intraglial inclusions composed of hyperphosphorylated microtubule-associated protein tau and ubiquitin. Missense and splice site mutations in the TAU gene have been identified in approximately 15% of all frontotemporal dementia cases. In this study, we evaluated the involvement of mutations in the TAU gene in development of frontotemporal dementia phenotype in patients of French or English Canadian origins. METHODS: Fourteen patients with frontotemporal dementia phenotype and 98 normal controls were recruited for the study. The TAU gene was screened by sequencing and denaturing high performance liquid chromatography. RESULTS: No mutations, except some new polymorphisms, were detected in the TAU gene of these patients. One polymorphism, however, may play a role in pathogenesis. CONCLUSION: Our results agree with previous work suggesting that mutations in this gene are not a frequent cause of the frontotemporal dementia phenotype in Canadian patients.     

Dysphagia in patients with frontotemporal lobar dementia

BACKGROUND: Hyperorality, compulsive eating and aspiration because of food gorging, has been described in patients with frontotemporal lobar dementia (FTLD), but swallowing function in this population has not been reported. OBJECTIVE: To identify the swallowing status in a sample of patients with FTLD. DESIGN: Case series. SETTING: Referral center, ambulatory care. PATIENTS: A consecutive series of referred patients with 3 variants of FTLD were asked to participate. Twenty-one patients were enrolled, including 9 with frontotemporal dementia, 7 with progressive nonfluent aphasia, and 5 with semantic dementia. INTERVENTION: The patients underwent a fiberoptic endoscopic examination of swallowing to assess their ability to swallow liquids and food. MAIN OUTCOME MEASURES: Presence of dysphagia and nature of impaired swallowing. RESULTS: Of the 21 patients, 4 caretakers reported swallowing difficulties. An instrumental examination revealed moderate swallowing abnormalities in 12 of the 21 patients. These abnormalities were not explained by compulsive eating behaviors, but seemed to reflect deficits in cortical and subcortical pathways connecting with the brainstem swallowing center. CONCLUSIONS: When assessed via instrumentation, swallowing abnormalities are found in many patients with FTLD. The appearance of dysphagia signals progression of FTLD to brainstem systems.     

Dementia with prominent frontotemporal features associated with L113P presenilin 1 mutation

The authors report a presenilin 1 (PSEN1) mutation (L113P) in a family with six cases of dementia. The patients had personality changes and behavioral disorders, whereas spatial orientation and praxis were preserved late in the course of the illness. Neuroimaging features were consistent with the diagnosis of frontotemporal dementia. The authors conclude that PSEN1 mutations can be associated with clinical features of frontotemporal dementia.     

A neuropsychological investigation of dementia in motor neurone disease (MND)

Different clinical criteria for diagnosing dementia were compared in a sample of 69 patients with motor neurone disease (MND). Participants’ performances on a computerised battery of neuropsychological tests were evaluated to assess the usefulness of these tests in predicting dementia in MND. The results indicated that when diagnostic criteria for frontotemporal (FTD) were used as part of a questionnaire method of diagnosing dementia the incidence of dementia in MND was considerably greater than traditional estimates suggest. Through a series of logistic and multiple regressions the results demonstrated that neuropsychological test performance related well to diagnostic classifications of dementia. MND patients with a clinical diagnosis of dementia were likely to demonstrate impaired new learning; poor working memory and planning; slowness in information processing and rigidity in thinking. These features, which are typical of cases of FTD, suggest that the dementia of MND is usefully characterised as a form of FTD. The finding that neuropsychological impairment correlated with behavioural features of dysexecutive impairment in daily living, indicates that the management focus in MND must be broadened to include cognitive/behavioural issues.