Shunichiro Shinagawa

Initial Symptoms in Frontotemporal Dementia and Semantic Dementia Compared with Alzheimer’s Disease

Background: Despite many reports about cognitive decline and behavioral changes in patients with frontotemporal lobar degeneration (FTLD), there have been very few systematic studies of initial symptoms of frontotemporal dementia (FTD) and semantic dementia (SD). Objective: It was the aim of this study to investigate FTD and SD and to establish whether they are characterized by different initial symptoms. Methods: Three groups of patients were studied: FTD (n = 36), SD (n = 17) and age-matched Alzheimer’s disease (AD) patients (n = 52). Information on initial symptoms was obtained from caregivers. Symptoms were classified into 22 distinct categories from the following domains, based on previous studies of symptoms of FTLD: (1) change in social behavior, affection, and daily activities, (2) cognitive decline, (3) language impairments, and (4) other abnormal symptoms. Results: Change in social behavior, affection, and daily activities was significantly more common in patients with FTD; on the other hand, language impairments were significantly more common in patients with SD as initial symptoms. Apathy and stereotypic behaviors were the most common initial symptoms among patients with FTD, while anomia, paraphasia, and impairment in word comprehension were the most common initial symptoms among patients with SD. Memory disturbance was the most common initial symptom among patients with AD. Conclusions: Behavioral and psychiatric symptoms are predominant initial symptoms in FTD, while language symptoms are predominant initial symptoms in SD. In addition to the assessment of current symptoms, the assessment of initial symptoms is useful for differential diagnosis in patients with FTD, SD and AD.

Increase in the IgG avidity index due to herpes simplex virus type 1 reactivation and its relationship with cognitive function in amnestic mild cognitive impairment and Alzheimer’s disease

After infection with herpes simplex virus type 1 (HSV-1), latent infection persists for life in the trigeminal ganglion and reactivation results in an outbreak of cold sores around the mouth. Many previous studies have reported HSV-1 reactivation to be a risk factor for Alzheimers disease (AD). This study enrolled subjects with AD (n=85), subjects with amnestic mild cognitive impairment (aMCI; a prodromal stage of AD) (n=34), and healthy controls (n=28). The avidity index of anti-HSV-1 IgG antibodies--a known indicator of HSV-1 reactivation--was measured in order to clarify the relationship between HSV-1 reactivation and symptoms of cognitive function in AD. Cognitive function in AD and aMCI were evaluated using scores from the mini-mental state examination (MMSE) and frontal assessment battery (FAB). The results showed that the subjects with aMCI, for which cerebral function is better preserved than subjects with AD, had a higher anti-HSV-1 IgG antibody avidity index than the AD subjects or healthy controls. Furthermore, the anti-HSV-1 IgG antibody avidity index was even higher in the subjects with high MMSE scores on orientation to time and three-step command subscores. We observed a negative correlation between the anti-HSV-1 IgG antibody avidity index and plasma BDNF concentration, which is an indicator of encephalitis. This suggests that HSV-1 reactivation, as observed through an increase in the anti-HSV-1 IgG avidity index, does not progress to encephalitis. These results suggest that HSV-1 reactivation occurs from the stage of aMCI, which is prodromal to AD, and can affect AD symptoms without an intermediary stage of severe encephalitis. The study demonstrates that the anti-HSV-1 IgG antibody avidity index could be a useful biomarker for the early diagnosis of aMCI as well as AD, and suggests that antiviral medication to treat HSV-1 could play a role in preventing the onset of AD.

Association between BDNF Polymorphism (Val66Met) and Executive Function in Patients with Amnestic Mild Cognitive Impairment or Mild Alzheimer Disease

Background: In the present study, we examined whether brain-derived neurotrophic factor (BDNF) polymorphism (Val66Met) influenced the changeable executive dysfunction of patients with two separate disease stages: amnestic mild cognitive impairment (A-MCI) or mild Alzheimer disease (AD), which are comparatively similar demented conditions. Methods: Among 200 outpatients with dementia and MCI, 146 outpatients with mild AD or A-MCI were recruited and divided into two genotypic groups, valine homozygosity (Val/Val) and methionine (Met) carriers, based on the representative BDNF functional polymorphism Val66Met. Next, we compared the Frontal Assessment Battery (FAB) total and subtest scores between the two genotypic groups according to each of two different disease stages: A-MCI (n = 42) and mild AD (n = 104). Results: Among patients with only a mild stage of AD, the FAB total and go/no-go scores were significantly lower (p < 0.05) among the subjects with the Val/Val genotype than among the Met carriers. However, no significant differences in any other demographic variables were observed between the genotypes according to each of different disease stages. A significant interaction between Val66Met and age was not observed for the FAB scores. Conclusion: These results suggested that the BDNF gene may significantly influence executive dysfunction, including inhibition tasks, among patients with mild-stage AD.

Association between executive dysfunction and hippocampal volume in Alzheimer's disease

BACKGROUND Some previous research has hypothesized that executive dysfunction in patients with early Alzheimers disease (AD) occurs as a result of a disconnection between different cerebral areas. The aim of the present study was to evaluate how the hippocampal volume influences executive function as a non-memory cognitive function. METHODS From 157 consecutive patients with AD or amnestic mild cognitive impairment (A-MCI), we recruited 107 subjects who had a global Clinical Dementia Rating (CDR) of 0.5 or 1.0 and whose degree of hippocampal atrophy had been measured using magnetic resonance imaging (MRI); the severity of atrophy was assessed using the voxel-based specific regional analysis for Alzheimers disease (VSRAD) system. We divided the subjects into three groups: mild atrophy, 0 < Z-score < 1.0 (N = 21); moderate atrophy, 1.0 ≤ Z-score < 2.0 (N = 46); or severe atrophy, 2.0 ≤ Z-score < 4.0 (N = 40) according to the Z-score and compared the Frontal Assessment Battery (FAB) and its subtest scores between each atrophy group. RESULTS The results demonstrated that age, sex ratio, duration of illness, education years, MMSE score, Behave-AD score, and proportion of atrophy area in total brain (%) were not significantly different among the three groups. Only the go/no-go score among the six subtests was significantly lower for increasing atrophy severity (P < 0.05). Furthermore, hippocampal atrophy significantly influenced the go/no-go score independently of interactions from whether the diagnosis was early AD or A-MCI (P < 0.05). CONCLUSION These results support a significant association between hippocampal atrophy and executive dysfunction as a non-memory cognitive impairment in patients with early AD and A-MCI.

Transition of Distinctive Symptoms of Semantic Dementia during Longitudinal Clinical Observation

Background/Aims: The aim of this study is to examine the clinical symptoms in a number of semantic dementia (SD) patients and to reveal the longitudinal progression and clinical course of these distinctive symptoms of SD. Methods: 19 consecutive SD patients were examined. Symptoms were classified into 23 distinct categories: behavioral symptoms, language and cognitive symptoms and symptoms concerning the impairment of activities of daily living (ADL). We divided patients into two subgroups, left- and right-dominant SD, and compared the onset of each symptom. Results: Language impairments occurred as the initial symptom in 16 cases. At the first examination, all cases showed both anomia and impairment of word comprehension. By around 3 years after onset, almost all language impairments were observed. Approximately 3–5 years after onset, prosopagnosia and behavioral symptoms appeared. Around the period when the loss of the language faculty and apathy became remarkable, impairment of ADL appeared. Patients spent all day in bed at this stage. Moreover, prosopagnosia appeared significantly earlier in right-dominant SD. Conclusion: Our findings clarify the progression of distinctive symptoms of SD patients. It is necessary to create a treatment strategy for SD patients with such a disease-specific course of SD.

Characteristics of abnormal eating behaviours in frontotemporal lobar degeneration: A cross-cultural survey

Frontotemporal lobar degeneration (FTLD) is characterised by behavioural changes, including loss of insight, disinhibition, apathy, mood changes, stereotypic behaviour and abnormal eating behaviour.1 2 Although many studies have highlighted the high prevalence of alterations in food preference and eating habits in FTLD and described loss of appetite in dementia represented by Alzheimer disease (AD),3 there have been few systematic studies comparing FTLD subgroups, or contrasting AD and FTLD.1 2 4 Eating behaviours are modulated by many factors including personal habits, ethnic culture and climate, such that alteration in eating behaviour in dementias may be confounded by ethnic or cultural factors. Food culture, meal styles and customs differ substantially between Western countries and Japan. People in the UK consume considerably more sweets, and total daily calorific intakes are higher than they are for the Japanese. (Data derived from the Food and Agriculture Organization of the United Nations; http://faostat.fao.org/.) Therefore, it is unclear whether altered eating behaviours of FTLD in Western cohorts are an entirely disease-specific effect or whether they are modulated by ethnic–cultural factors. The aims of this study were to investigate changes in eating behaviours in Japanese FTLD and AD patients and to compare the profile of abnormal eating behaviours in Japanese and Western patients using the same …

Mirtazapine improves visual hallucinations in Parkinson's disease: a case report

Psychotic symptoms often occur as a complication in Parkinsons disease patients, and a set of criteria for Parkinsons disease with psychosis (PDPsy) has been established. Among these criteria, hallucinations are one of the specific symptoms, with visual hallucinations being the most common. While atypical antipsychotic agents are often used for the treatment of PDPsy, adverse effects, including extrapyramidal symptoms, often hinder its continuation or tolerance. There have been some reports and reviews indicating that antidepressants may be effective for PDPsy and other forms of dementia with psychosis. In this report, we present a patient with PDPsy who was treated with one of the new‐generation antidepressants, mirtazapine. Mirtazapine improved the patients refractory psychotic symptoms, especially her visual hallucinations, without worsening her motor symptoms.

Correlation between a reduction in Frontal Assessment Battery scores and delusional thoughts in patients with Alzheimer's disease

Aims:  The purpose of the present study was to investigate the relationship between delusional thoughts (delusional ideation or misidentification) and frontal lobe function using the Japanese version of the Frontal Assessment Battery (FAB) bedside screening neuropsychological test in early stage Alzheimers disease (AD) patients.

Association between brain-derived neurotrophic factor (BDNF) gene polymorphisms and executive function in Japanese patients with Alzheimer's disease

Background:  To address the functional roles of genetic polymorphisms of brain‐derived neurotrophic factor (BDNF) in Alzheimers disease (AD) from a neuropsychological aspect, we used a cross‐sectional study design to investigate the association between novel single nucleotide polymorphisms (SNPs) of the BDNF gene (Val66Met (G196A) and C270T) and the Frontal Assessment Battery (FAB) score, which reflects executive function as a non‐memory cognitive impairment.

Differentiation between amnestic-mild cognitive impairment and early-stage Alzheimer's disease using the Frontal Assessment Battery test

Background:  Previous research has described the executive dysfunction that occurs in patients with amnestic‐mild cognitive impairments (A‐MCI) and early‐stage Alzheimers disease (EAD), which are comparatively similar stages of dementia. The aim of the present cross‐sectional study is to evaluate executive dysfunction using the Frontal Assessment Battery (FAB) screening test in two groups and to investigate the interaction with other cognitive impairments.