Risk factors of frontotemporal dementia compared with Alzheimer disease: Single psychiatric hospital-based research in Japan.

AIM: The objective of this study was to reveal risk factors for incident of frontotemporal dementia (FTD) compared with Alzheimer disease (AD) in Japan. METHOD: Fifty consecutive subjects diagnosed with FTD according to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) under 75 years old were included retrospectively. As a control group, 48 subjects who were diagnosed with AD according to the DSM-5 and matched by age, sex, educational history, and Mini-Mental State Examination were also included. In order to examine the distinctive risk factors of FTD, we compared the relationship between symptomatologic features, Clinical Dementia Rating, clinical factors, and sociopsychological factors in the two groups. RESULT: Patients with FTD were more likely than patients with AD to have meticulous premorbid personality and less likely to have a history of diabetes than patients with AD. Although the regression analysis was not significant, a history of psychiatric disorders tends to affect the incidence of FTD. CONCLUSIONS: These findings regarding the risk of FTD are expected to lead to early diagnosis and care of FTD. Geriatr Gerontol Int 2023; 23: 932-937.

Pathogenesis and Personalized Interventions for Pharmacological Treatment-Resistant Neuropsychiatric Symptoms in Alzheimer's Disease.

Alzheimer's disease (AD) is the most common form of dementia, with cognitive impairment as a core symptom. Neuropsychiatric symptoms (NPSs) also occur as non-cognitive symptoms during the disease course, worsening the prognosis. Recent treatment guidelines for NPSs have recommended non-pharmacological treatments as the first line of therapy, followed by pharmacological treatments. However, pharmacological treatment for urgent NPSs can be difficult because of a lack of efficacy or an intolerance, requiring multiple changes in psychotropic prescriptions. One biological factor that might be partly responsible for this difficulty is structural deterioration in elderly people with dementia, which may cause a functional vulnerability affecting the pharmacological response. Other causative factors might include awkward psychosocial interpersonal relations between patients and their caregiver, resulting in distressful vicious circles. Overlapping NPS sub-symptoms can also blur the prioritization of targeted symptoms. Furthermore, consistent neurocognitive reductions cause a primary apathy state and a secondary distorted ideation or perception of present objects, leading to reactions that cannot be treated pharmacologically. The present review defines treatment-resistant NPSs in AD; it may be necessary and helpful for clinicians to discuss the pathogenesis and comprehensive solutions based on three major hypothetical pathophysiological viewpoints: (1) biology, (2) psychosociology, and (3) neurocognition.

Education level is associated with neuropsychiatric symptoms in patients with amnestic-mild cognitive impairment.

BACKGROUND: We examined differences in the severity of neuropsychiatric symptom (NPS) subsyndromes according to education level among patients with amnestic-mild cognitive impairment (a-MCI) with the aim of identifying patient demographics related to NPS subsyndromes. METHODS: Overall, 140 patients with a-MCI were included. We divided the patients into three groups according to their educational level (primary education, middle education, and high education) and compared their demographics. To explore the severity of NPS subsyndromes according to educational level, we used the Neuropsychiatric Inventory (NPI) after adjustments for the Mini-Mental State Examination (MMSE) score. Finally, NPS subsyndromes that were identified as being related to educational level were further explored using a general linear model (GLM). RESULTS: Significant differences in several demographics were observed among the three groups. Among the NPS subsyndromes, the scores for aggressiveness were significantly higher in the primary and high education groups than in the middle education group, while the apathy/eating problem scores were significantly higher in the primary education group than in the other groups. The GLM analyses showed that aggressiveness was related to marital status and the Zarit Caregiver Burden Interview (ZBI-J) score, while apathy/eating problems were related to the instrumental activities of daily living (IADL) percentage, the ZBI-J score, and the education level in years. CONCLUSIONS: Among NPS subsyndromes, aggressiveness and apathy/eating problems differed according to education level in patients with a-MCI. A GLM analysis suggested that not only education level, but also various other factors should be considered when determining the need for NPS interventions.

Clinicodemographic and Psychosocial Factors Related to Presentation or Severity of Delusions of Theft among Females with Amnestic Mild Cognitive Impairment and Alzheimer's Disease.

Objectives: We examined the clinicodemographic and psychosocial factors that relate to the presentation and severity of delusions of theft among female patients with amnestic mild cognitive impairment (a-MCI) and Alzheimer's disease (AD).Methods: We enrolled a total of 177 female patients with a-MCI or AD, of whom 40 presented with delusions of theft. We compared the differences in clinicodemographic and psychosocial factors of the 40 patients (delusions of theft group) with 50 age- and Mini-Mental State Examination (MMSE)-matched controls without delusions (control group). Furthermore, we identified the factors associated with the presentation of delusions of theft using a general linear model (GLM). The severity of delusions of theft was calculated using the Neuropsychiatric Inventory Questionnaire, and correlations between the clinicodemographic and psychosocial factors were examined.Results: Between the two groups, the delusions of theft group had lower scores on the Physical Self-Maintenance Scale and instrumental activities of daily living (IADL) and higher scores on the Japanese version of the Zarit Caregiver Burden Interview (ZBI-J) than the control group. GLM analysis revealed that the IADL score was related to the presentation of delusions of theft. The severity of delusions of theft correlated with the MMSE and the ZBI-J scores in the delusions of theft group.Conclusions: The two groups had several differences regarding clinicodemographic and psychosocial factors. Furthermore, lower IADL scores were related to symptom presentation. Symptom severity correlated with cognitive functioning and caregiver burden.Clinical Implications: In the determination of treatment or care, differences in these factors should be considered.

Associations between parental bonding during childhood and functional recovery in patients with schizophrenia.

INTRODUCTION: Schizophrenia is believed to be etiologically associated with environmental factors. Poor parental bonding, especially arising from "low care" and "overprotection," may contribute to the prognosis in patients with psychosis. In the present study, we investigated the associations between the aforementioned two different parental bonding types and the prognosis, in terms of the functional recovery, of patients with schizophrenia. METHODS: A total of 89 patients with schizophrenia were recruited, and 79 patients were registered for the study. After the parental bonding types and representative childhood adverse events were assessed, specific items on the PANSS were assessed at 0 and 24 weeks of the study period to define the functional prognosis. RESULTS: At the end of the 24-week follow-up period, 36% of the patients were judged as showing recovery from schizophrenia. The score for "overprotective attitude," but not that for "low care," was found to be significantly higher in the non-recovery (defined below) group. Exploratory logistic regression analysis identified only "overprotective attitude" of the parents as being predictive of non-recovery. Moreover, a significant negative correlation was found between "low care" and "overprotective attitude" only in the non-recovery group. CONCLUSION: In the present study, we showed that an overprotective attitude of the parents was associated with non-recovery in patients with schizophrenia.

Effects of neuropsychiatric symptoms of dementia on reductions in activities of daily living in patients with Alzheimer's disease.

AIM: In patients with Alzheimer's disease (AD), cognitive impairments cause a progressive reduction in Activities of Daily Living (ADL). Neuropsychiatric symptoms (NPS) also appear in most patients; however, the association between NPS and reductions in ADL remains unclear. The present study evaluated whether NPS influence such reductions using two different ADL measures in patients with AD. METHODS: Among 546 consecutive outpatients who visited the memory clinic at the Jikei University Kashiwa Hospital, we recruited 208 patients with AD and investigated the correlations between either the Physical Self-Maintenance Scale (PSMS) score or the Instrumental ADL (IADL) level, and each of the Behavioral Pathology in AD (Behave-AD) subscales. To clarify the causal relationships of these correlations, we then verified the associations between statistically significant demographic variables and the Behave-AD subscales as well as the two ADL scales (PSMS score and IADL percentage) using a general linear model. RESULTS: Neither the PSMS nor the IADL results were significantly influenced by the aberrant motor behaviors score. However, the IADL was significantly influenced by the Mini-Mental State Exam (MMSE) score. Furthermore, diurnal rhythm disturbances and the interaction between diurnal rhythm disturbances score and the MMSE score significantly influenced the PSMS results. CONCLUSION: Basic ADL reductions may be influenced by diurnal rhythm disturbances, in addition to cognitive impairments in patients with AD. Furthermore, the interaction between the diurnal rhythm disturbances score and cognitive function may also influence basic ADL. Geriatr Gerontol Int 2020; ••: ••-••.

Sex differences in the severity of neuropsychiatric symptoms and their relationship with clinico-demographic and psychosocial factors in patients with amnestic mild cognitive impairment and mild Alzheimer's disease.

Objectives: We examined differences in the severity of neuropsychiatric symptoms (NPS) according to sex and identified NPS-related clinico-demographic and psychosocial factors among community-living patients with amnestic-mild cognitive impairment (a-MCI) or mild Alzheimer's disease (AD).Method: Overall, 111 patients (44 males, 67 females) with mild a-MCI (n = 64) or mild AD (n = 47) were included. We divided the patients according to sex and compared their clinico-demographic and psychosocial factors, explored the severity of NPS using the subscales from the Neuropsychiatric Inventory-Questionnaire (NPI-Q), and further identified variables related to NPS.Results: Significant differences in several clinico-demographic and psychosocial characteristics were observed between the sexes. The severity of delusions was higher among females (mean, 0.48; SD, 1.60) than males (mean, 0.23; SD, 1.07; p = .02), while the severity of irritability was higher among males (mean, 0.97; SD, 1.92) than females (mean, 0.49; SD, 1.40; p = .03). The severity of delusions among females was related to the duration of cognitive decline (B = 0.37, p = .03), while the severity of irritability among males was related to general cognition (B = -0.40, p = .003).Conclusion: The severity of NPS among patients with a-MCI or mild AD differed according to sex. We identified NPS-related clinico-demographic factors among these patients. Sex differences should be considered when determining the need for NPS interventions.

Anosognosia in mild Alzheimer's disease is correlated with not only neural dysfunction but also compensation.

BACKGROUND: Anosognosia in Alzheimer's disease (AD) is a complicated, non-unitary phenomenon. In a clinical setting, patients with mild AD often preserve their awareness partially. We hypothesized that compensation, as well as neural dysfunction, could be correlated with anosognosia in mild AD. METHODS: The severity of anosognosia was evaluated using the Anosognosia Questionnaire for Dementia in 37 subjects with mild AD or mild cognitive impairment due to AD. The subjects also underwent single-photon emission computed tomography with N-isopropyl-p-[123 I]iodoamphetamine. Correlation between the severity of anosognosia and perfusion was assessed, and anosognosia (+) and (-) groups were compared. RESULTS: The severity of anosognosia was relatively mild; the mean Anosognosia Questionnaire for Dementia score was 6.76 ± 14.16. Subjects were divided into two groups: anosognosia (+) (n = 11) and anosognosia (-) (n = 26). In the single-photon emission computed tomography data analysis, the severity of anosognosia was correlated with both lower regional cerebral blood flows of the right prefrontal cortex and higher regional cerebral blood flows of the parietal cortex, especially the left temporo-parietal junction. CONCLUSIONS: Our results suggest that anosognosia in mild AD could be correlated with compensation as well as neural dysfunction. We speculate that this compensation may be related to the retrieval of outdated autobiographical memory.

Executive Dysfunction Correlated With 2-Year Treatment Response in Patients With Late-Life Undifferentiated Somatoform Disorders.

BACKGROUND: Late-life somatoform disorders (SDs) are characterized by various aging-associated factors. Recently, cognitive decline, including executive dysfunction, has been reported as an etiological factor of late-life SDs. The response to treatment for late-life SDs varies from one patient to another. Treatment strategies for late-life SDs require these etiological factors to be considered. We hypothesized that the treatment response in patients with late-life SDs was associated with executive dysfunction. OBJECTIVE: The aim of the present study was to confirm the changes in disease severity over a 2-year follow-up period and to determine which etiological factors are related to the treatment response in patients with late-life SDs. METHODS: We examined 55 patients with late-life SDs who were treated with pharmacotherapy and supportive psychotherapy at baseline. The changes in the disease severity and cognitive profiles over a 2-year follow-up period were evaluated. Additionally, we investigated which etiological factors at baseline were related to treatment resistance. RESULTS: Of the 55 patients who were enrolled in the present study, 31 completed the 2-year follow-up period. Overall, the disease severity improved significantly in patients with late-life SDs. On the contrary, executive function decreased throughout the research period. Moreover, we found that executive dysfunction and the presence of hyperlipidemia at baseline were related to treatment resistance. CONCLUSIONS: These results suggest that aging-associated etiological factors be considered for the treatment of late-life SDs.

White matter hyperintensities are associated with the severity of late-life somatoform disorders and executive functions.

BACKGROUND: Medically unexplained symptoms are often seen in the elderly. Recently, correlations between medically unexplained symptoms and somatoform disorders (SDs) have been reported. The existence of many interactive psychiatric aetiologies is known among SDs. Late-life SDs might be influenced by some aetiological factors caused by ageing processes, such as structural changes in the brain and cognitive dysfunctions. AIMS: Under such circumstances, we investigated the presence of subcortical white matter hyperintensities (WMHs), which increase with ageing, and hypothesized that subcortical WMHs are related to the disease severity of late-life SDs. Furthermore, we confirmed whether cognitive dysfunction influences this process. METHODS: To evaluate these hypotheses, we examined patients with medically unexplained symptoms who met the criteria for undifferentiated somatoform disorder and divided the patients into three groups according to the degree of subcortical WMHs: grade 0, grade 1, and grade 2. The subcortical WMHs were rated using Fazekas grading. Differences in symptom severity and cognitive functions were compared among the three groups. RESULTS: The grade 2 group had the severest symptoms. Furthermore, the grade 2 group had lower cognitive function scores than the other groups. CONCLUSIONS: The present study showed that the presence of subcortical WMHs in patients with late-life SDs was a predictor of disease severity. Moreover, cognitive dysfunction appeared to play a role in the advancement of disease severity.

Cognitive Dysfunction in Patients With Late-Life Somatic Symptom Disorder: A Comparison According to Disease Severity.

BACKGROUND: Late-life somatic symptom disorder (SSD) is characterized by various aging-associated factors, such as a functional decline, psychosocial problems, and cognitive dysfunction. However, the details of the cognitive dysfunction that occur in late-life SSD are still unknown. OBJECTIVE: The aims of this study were to reveal the cognitive profile of patients with late-life SSD and to evaluate how cognitive dysfunction affects disease severity. METHODS: We compared the cognitive profiles of patients with late-life SSD (n = 40) with those of normal control subjects (n = 21). In addition, we divided the patients with late-life SSD into mild-to-moderate (n = 24) and severe (n = 16) groups and compared the cognitive profiles of the 3 groups. RESULTS: Patients with late-life SSD exhibited a lower Mini-Mental State Examination total score and attention decline. In the 3-group comparison, the severe group had a lower Mini-Mental State Examination score and Frontal Assessment Battery score than the normal control group, whereas no significant difference was seen between the mild-to-moderate and the normal control groups. CONCLUSIONS: Our data suggest that different cognitive patterns may exist depending on disease severity, possibly indicating differences in pathogenesis.

Correlation between cognition and symptomatic severity in patients with late-life somatoform disorders.

OBJECTIVES: Various aging associated factors, such as functional decline, psychosocial problems, and cognitive dysfunction, are risk factors for somatoform disorders (SDs) in the elderly. The aim of the present study was to evaluate how cognition is correlated with the severity of late-life SDs from a neuropsychological viewpoint. METHODS: Fifty-three patients over 60 years of age who had been diagnosed as having SDs were examined in this study. The severity of the somatic symptoms was assessed using the Hamilton Anxiety Rating Scales (HAMA). Cognitive functions were assessed using the Mini-Mental State Examination (MMSE), the Frontal Assessment Battery (FAB), and the Japanese version of the Neurobehavioral Cognitive Examination (J-COGNISTAT). RESULTS: The J-COGNISTAT subtest score for attention was below the cutoff point (8 points) but was not correlated with the severity of the somatic symptoms in the patients with late-life SDs. The severity of anxiety as assessed using the HAMA was significantly correlated with the calculation scores (P < 0.005) among the J-COGNISTAT subtests, the FAB total (P < 0.05), and the FAB subtest scores (similarities and motor series) (P < 0.01). Other factors, including the benzodiazepine dosage, antidepressant dosage, the duration of illness, and the onset age, were not significantly correlated with the symptomatic severities. CONCLUSION: Patients with late-life SDs showed attention deficits, but no correlation was seen between the attention deficits and symptomatic severities. Attention deficits might be associated with the appearance of symptoms. Executive dysfunction and working memory might be associated with the severity of symptoms.

Correlation between both morphologic and functional changes and anxiety in Alzheimer's disease.

INTRODUCTION: Although anxiety symptoms are often observed in Alzheimer's disease (AD), little attention has been paid to this symptom compared with other neuropsychiatric symptoms. METHODS: Twenty-six patients with mild AD underwent both magnetic resonance imaging and single photon emission tomography with technetium-99m ethyl cysteinate dimer. Neuropsychiatric symptoms were evaluated using the Behavioral Pathology in Alzheimer's Disease Scale (Behave-AD). We investigated the relationship between anxiety and neuroimaging using Statistical Parametric Mapping 8 software. RESULTS: The Behave-AD anxiety score was correlated with hyperperfusion in the bilateral anterior cingulate cortices and a reduction in the gray matter volume in the right precuneus and inferior parietal lobule. CONCLUSION: Our results suggest that anxiety in AD could overlap with the neural correlates of anxiety disorders, and that the specific degeneration associated with AD might be associated with anxiety.