Clinical concept of frontotemporal dementia

The clinical concept of frontotemporal dementia is reviewed by discussing its relationships to several related concepts. These include dementia of the frontal lobe type, slowly progressive aphasia without dementia or primary progressive aphasia, semantic dementia and frontotemporal lobar degeneration. A number of examples of confusion in the terminology are also examined.     

Distinct white matter injury associated with medial temporal lobe atrophy in Alzheimer's versus semantic dementia

This study aims at further understanding the distinct vulnerability of brain networks in Alzheimer's disease (AD) versus semantic dementia (SD) investigating the white matter injury associated with medial temporal lobe (MTL) atrophy in both conditions. Twenty‐six AD patients, twenty‐one SD patients, and thirty‐nine controls underwent a high‐resolution T1‐MRI scan allowing to obtain maps of grey matter volume and white matter density. A statistical conjunction approach was used to identify MTL regions showing grey matter atrophy in both patient groups. The relationship between this common grey matter atrophy and white matter density maps was then assessed within each patient group. Patterns of grey matter atrophy were distinct in AD and SD but included a common region in the MTL, encompassing the hippocampus and amygdala. This common atrophy was associated with alterations in different white matter areas in AD versus SD, mainly including the cingulum and corpus callosum in AD, while restricted to the temporal lobe — essentially the uncinate and inferior longitudinal fasciculi — in SD. Complementary analyses revealed that these relationships remained significant when controlling for global atrophy or disease severity. Overall, this study provides the first evidence that atrophy of the same MTL region is related to damage in distinct white matter fibers in AD and SD. These different patterns emphasize the vulnerability of distinct brain networks related to the MTL in these two disorders, which might underlie the discrepancy in their symptoms. These results further suggest differences between AD and SD in the neuropathological processes occurring in the MTL. Hum Brain Mapp 38:1791–1800, 2017. © 2017 Wiley Periodicals, Inc.     

Two cases of food aversion with semantic dementia

ABSTRACT

Accounts of altered eating behavior in semantic dementia generally emphasize gluttony and abnormal food preferences. Here we describe two female patients with no past history of eating disorders who developed early prominent aversion to food in the context of an otherwise typical semantic dementia syndrome. One patient (aged 57) presented features in line with anorexia nervosa while the second patient (aged 58) presented with a syndrome more suggestive of bulimia nervosa. These cases add to the growing spectrum of apparently dichotomous behavior patterns in the frontotemporal dementias and illustrate a potentially under-recognized cause of eating disorders presenting in later life.     

Sentence processing in frontotemporal dementia

Patients with frontotemporal dementia (FTD) have sentence comprehension difficulty. We examined the hypothesis that both grammatical and resource factors contribute to their impaired sentence comprehension with a traditional, off-line sentence comprehension task, and an on-line sentence processing procedure that minimizes task-related resources. This was investigated in subgroups of FTD patients with Progressive Non-fluent Aphasia (PNFA; n = 5) who have effortful speech; non-aphasic patients with an executive deficit (EXEC; n = 8); and Semantic Dementia (SD; n = 3) patients with poor single word comprehension. The results were correlated with measures of executive resources. We found that PNFA patients are significantly impaired in their off-line sentence comprehension, and that their performance correlated with auditory-verbal short-term memory. PNFA patients also demonstrated a pattern of slowed processing for the on-line sentence measure. This is consistent with the hypothesis that information relevant for constructing sentence representations during comprehension degrades in working memory as it is activated over an abnormally slowed time course. EXEC patients had modest off-line sentence comprehension difficulty, and this correlated with performance on measures of working memory, planning, and inhibitory control. On-line processing in EXEC patients demonstrated their insensitivity to sentence-based information. This raises the possibility that a limitation in material-neutral executive resources not dedicated to grammatical processing may play a role in their sentence comprehension deficit. SD patients' pattern of on-line sentence comprehension paralleled control subjects' performance. We conclude that grammatical and executive components both contribute to sentence comprehension, and that the profile of sentence comprehension difficulty varies across FTD subgroups depending on the sentence processing component that is impaired.     

Five cases of frontotemporal dementia with behavioral symptoms improved by Yokukansan

Herein, we present five cases with frontotemporal dementia whose behavioral symptoms were improved by Yokukansan, a traditional Japanese medicine (Kampo). All five patients were prescribed Yokukansan (7.5 g/day) to reduce their symptoms. The patients' symptoms were evaluated comprehensively using the Neuropsychiatric Inventory (NPI) and the Stereotypy Rating Inventory (SRI) before and 4 weeks after Yokukansan treatment. The mean (± SD) scores on the NPI and the SRI before treatment were 55.6 ± 5.4 and 22.2 ± 6.5, respectively. After treatment, these scores were 30.0 ± 7.8 and 11.6 ± 7.5, respectively. Yokukansan was effective for the treatment of clinical symptoms in all five patients without adverse effects and significant changes in laboratory data. Although antipsychotic drugs have been used to control behavioral symptoms, their associated adverse effects frequently impact on the activities of daily living and quality of life of treated patients. The present cases suggest significant improvement of behavioral symptoms in frontotemporal dementia with Yokukansan treatment, leading to probable benefit of the use of Yokukansan in individuals with frontotemporal dementia.     

A case of progressive non-fluent aphasia as onset of amyotrophic lateral sclerosis with frontotemporal dementia

The association between Amyotrophic Lateral Sclerosis (ASL) and FrontoTemporal Dementia (FTD) is well known. Most of reports describing ASL-FTD cases show a strong association between ALS and the behavioural form of FTD. Conversely, the association between ALS and pure Semantic Dementia or Progressive Non-Fluent Aphasia (PNFA) is extremely rare, ranging from 1 to 3%. A clinical phenotype characterized by a rapidly progressive aphasic dementia and motoneuron disease (MND) has been described in few case reports; since the updating of PNFA diagnostic criteria in 2011, no clinical report has been related. We want to describe a case of patient presented, at the onset, as PNFA who developed, one year later, ALS with bulbar onset. The patient was screened for the main genes causing or associated with MND and/or dementia but no variants with a pathogenetic effect were observed.     

Dementia with Lewy bodies presenting as frontotemporal dementia phenotype

We herein report two patients with dementia with Lewy bodies (DLB) presenting characteristic symptoms suggestive of the behavioural variant of frontotemporal dementia (bvFTD). Patient 1 presented behavioural and personality changes from the onset, such as restlessness, compulsive behaviours, and stereotypical speech. A neuroimaging study showed preferential frontal involvement, and this patient fulfilled the diagnostic criteria for bvFTD. However, ¹²³I‐metaiodobenzylguanidine cardiac scintigraphy revealed a markedly lowered uptake, suggesting the diagnosis of possible DLB. Patient 2 fulfilled the criteria for probable DLB, but later presented bvFTD‐like symptoms similar to those in patient 1. These patients suggest that DLB can be a candidate for differential diagnosis of bvFTD in the clinical setting.     

Cognitive and behavioral profile in a case of right anterior temporal lobe neurodegeneration

Semantic dementia (SD) is a clinical variant of frontotemporal lobar degeneration (FTLD) characterized by progressive deterioration of semantic memory with relative sparing of other cognitive functions. It is associated with mainly left anterior temporal atrophy, and is also referred to as “left-temporal lobe variant” of FTLD. Recently, patients with mainly right-sided atrophy, or “right-temporal lobe variant”(RTLV), have been described. While some authors have reported that the initial and most significant deficit in these right-sided cases is a difficulty in recognizing famous people, others have observed that major behavioral abnormalities are the presenting symptoms. Here we report a detailed neuropsychological, language, behavioral and neuroimaging assessment of JT, a case of right temporal lobe variant of FTLD. JT showed early and prominent behavioral changes accompanied by a severe impairment in recognizing foods by their look, flavor or name. Later she also developed a difficulty in recognizing familiar people and objects. Standardized caregiver questionnaires of JT's pre- and post-morbid personality and interpersonal functioning showed that she went from being a flexible, dominant, extraverted, person to showing rigid, submissive and introverted behaviors. Her levels of neuroticism significantly increased, while her scores on agreeableness and cognitive and emotional empathy dropped. Voxel-based morphometry (VBM) showed most significant atrophy in the right amygdala/anterior hippocampal complex and collateral sulcus, extending to the right insula. We discuss the atypical cognitive and behavioral features of this case of RTLV of FTLD and stress the importance of behavioral changes and atypical semantic deficits for early diagnosis.     

A 6-month, open-label study of memantine in patients with frontotemporal dementia

OBJECTIVE: To evaluate safety and effects on cognition and behavior of memantine 20 mg/day in the treatment of patients with frontotemporal dementia (FTD). METHODS: This was a single-center, 6-month, open, uncontrolled study. Sixteen outpatients with a diagnosis of FTD were enrolled. RESULTS: On the CIBIC plus 26 weeks after baseline four of the 16 patients were minimally improved, four were unchanged, seven were minimally worse and one patient was moderately worse. Neither the Neuropsychiatric Inventory nor the Frontal Behavioral Inventory demonstrated statistically significant differences in behavior between baseline and final visit. There was an increase in the total Alzheimer's Disease Assessment Scale score, reflecting a decline in cognitive performance. Executive functions as well as activities of daily living and extrapyramidal motor symptoms (EPMS) remained unchanged during the trial. CONCLUSION: The number of patients was small, so that the evidence given by statistical tests is limited. Thus, the present study can only show trends regarding drug effects. As memantine is well-tolerated, further randomized and controlled studies should be conducted to evaluate drug efficacy.     

The topographic distribution of brain atrophy in frontal lobe dementia

Summary The topographic distribution of brain atrophy was quantified by image analysis of fixed brain slices from ten patients dying with dementia of frontal type (DFT) and from six other patients dying with dementia of frontal type with motor neurone disease (DFT+MND). In both groups the atrophy was maximal within frontal, anterior temporal and anterior parietal regions of cortex, although other structures such as the amygdala, caudate nucleus, thalamus and hippocampus were also affected. The magnitude of the atrophy was much greater, in all affected regions, in DFT alone than in DFT+MND. Grey and white matter were affected equally in DFT alone although in DFT+MND a preferential white matter involvement was noted. No differences in the topographic distribution of the atrophy was observed in cases of DFT showing a spongiform degeneration of the cortex compared to those showing a gliotic degeneration with, or without, Pick cells and Pick bodies.Supported by a studentship (to PWS) from the Zochonis Foundation     

Personality traits and frontal lobe dementia

The diagnosis of frontal lobe dementia (FLD) involves the assessment of affect. Three affective states predominate in FLD: apathy, elation and emotionalism. Nineteen FLD patients were investigated for a relationship between affective changes and premorbid personality traits. The negative results support the hypothesis that mood changes in FLD have a neurological basis and are important in early diagnosis.     

The heterogeneity of frontotemporal dementia with regard to initial symptoms, qEEG and neuropathology

OBJECTIVES/METHODS: Ten patients with neuropathologically verified frontotemporal dementia (FTD) were analysed for neuropathological features in relation to first presenting and dominating symptoms, age at onset and duration of dementia, as well as to EEG/quantitative EEG. RESULTS: Cases with a late onset (> 65 years) initially presented language disturbances, while the early onset group (< 65 years) showed predominantly behavioural symptoms and mood alterations as early features. The late onset group presented combined cortical-subcortical degeneration including white matter pathology, while early onset cases showed pathology predominantly in the cortex. EEG was normal in the late onset group, while it was mildly and variably abnormal in those with early onset. CONCLUSIONS: Within this small sample of clinical and neuropathological FTD, cases with late vs early onset differed with respect to initial symptoms, EEG findings and regional distribution of brain pathology.     

Support to family carers of patients with frontotemporal dementia

Objectives: To examine the provision of support to patients with frontotemporal dementia (FTD) and their family carers compared with patients with early onset Alzheimer's dementia (AD) and their carers, and the carers' satisfaction with the support. Method: Data came from 60 dyads of patients with dementia and their principal family carers, 23 subjects with frontotemporal dementia and their 23 carers, and 37 subjects with early onset Alzheimer's disease and their 37 carers. Results: Patients with a frontotemporal dementia diagnosis were significantly more frequently offered stays in nursing homes (p = 0.04). Carers of patients with frontotemporal dementia were significantly less satisfied with the provision of information about the disease compared with carers of early onset Alzheimer's disease patients (p = 0.05) and were significantly less satisfied with counseling and follow-up advice (p = 0.05). Conclusion: Changes of personality in patients with frontotemporal dementia may be the major reason why they were offered more stays in institutions. These family carers tend to be less satisfied with the provision of support they received from the specialist health service compared to carers of Alzheimer's disease patients, and are in need of more, and other forms of support.     

Quantitative EEG and medial temporal lobe atrophy in Alzheimer's dementia: Preliminary study

Backgrounds:

The electroencephalogram (EEG) abnormalities in Alzheimer''s disease (AD) have been widely reported, and medial temporal lobe atrophy (MTLA) is one of the hallmarks in early stage of AD. We aimed to assess the relationship between EEG abnormalities and MTLA and its clinical validity.

Materials and Methods:

A total of 18 patients with AD were recruited (the mean age: 77.83 years). Baseline EEGs were analyzed with quantitative spectral analysis. MTLA was assessed by a T1-axial visual rating scale (VRS).

Results:

In relative power spectrum analysis according to the right MTLA severity, the power of theta waves in C4, T4, F4, F8, and T5 increased significantly and the power of beta waves in T6, C4, T4, F8, T5, P3, T3, and F7 decreased significantly in severe atrophy group. In relative power spectrum analysis according to the left MTLA severity, the power of theta waves in T3 increased significantly and that of beta waves in P4, T6, C4, F4, F8, T5, P3, C3, T3, F3, and F7 decreased significantly in severe atrophy group.

Conclusion:

The severe MTLA group, regardless of laterality, showed more severe quantitative EEG alterations. These results suggest that quantitative EEG abnormalities are correlated with the MTLA, which may play an important role in AD process.