It May Not Be So Typical: Distinguishing Frontotemporal Dementia From Behavioral Variant Alzheimer's Disease.

The Banner Alzheimer's Institute Case Conference is a weekly event in which physicians and staff discuss challenging and/or teaching cases of patients seen in clinical settings. These conferences are attended by a multidisciplinary group that includes Banner Alzheimer's Institute dementia specialists, community physicians (internal medicine, family medicine, and radiology), neuropsychologists, physician assistants, nurse practitioners, social workers, medical students, residents, and fellows. The Banner Alzheimer's Institute is located in Phoenix, Arizona, and it has an ambitious mission: to end Alzheimer's disease without losing a generation, set a new standard of care for patients and families, and forge a model of collaboration in biomedical research. The Institute provides high-level care and treatment for patients affected by Alzheimer's disease, dementia, and related disorders. In addition, the Institute offers extensive support services for families and many unique and rewarding research opportunities.

Hirami lemon (Citrus reticulata var. depressa) modulates the gut-brain axis in a chronic mild stress-induced depression mouse model.

Citrus reticulata var. depressa, commonly known as Hirami lemon, is a native citrus species found in Taiwan and Okinawa islands of Japan. While several Citrus species are known to possess antidepressant activity by modulating the gut microbiota, the antidepressant effect of Hirami lemon and its underlying mechanisms have not been thoroughly investigated. In this study, we explored the potential antidepressant efficacy of the fruit extract (CD) and the essential oil (CDE) from Hirami lemon peel using a chronic mild stress (CMS)-induced mouse model and analyzed the association of gut microbiome changes. Our findings revealed that mice subjected to CMS exhibited anxiety- and depression-like behaviors as assessed by elevated plus-maze and forced swimming tests, respectively. Significantly, oral administration of CDE and CD notably reversed CMS-induced depression- and anxiety-like behaviors in CMS-induced mice. Moreover, compared to the non-stressed group, CMS significantly altered the gut microbiome, characterized by highly diverse bacterial communities, reduced Bacteroidetes, and increased Firmicutes. However, oral administration of CDE and CD restored gut microbiota dysbiosis. We also performed a qualitative analysis of CD and CDE using UPLC-MS and GC-MS, respectively. The CD contained 25 compounds, of which 3 were polymethoxy flavones and flavanones. Three major compounds, nobiletin, tangeretin and hesperidin, accounted for 56.88% of the total relative peak area. In contrast, the CDE contained 11 terpenoids, of which 8 were identified as major compounds, with D-limonene (45.71%) being the most abundant, followed by γ-terpinene (34.65%), linalool (6.46%), p-cymene (2.57%), α-terpineol (2.04%), α-pinene (1.89%), α-terpinolene (1.46%), and ß-pinene (1.16%), accounting for 95.94% of the total oil. In conclusion, our study demonstrated the potential of Hirami lemon as a source of natural antidepressant agents for the prevention and treatment of major depressive disorders.

No MMSE for You! A Case of an "Uncooperative" Patient With Early-Onset Dementia.

The Banner Alzheimer's Institute Case Conference is a weekly event in which physicians and staff discuss challenging and/or teaching cases of patients seen at the Institute's Stead Family Memory Clinic. These conferences are attended by a multidisciplinary group that includes Banner Alzheimer's Institute dementia specialists, community physicians (internal medicine, family medicine, and radiology), physician assistants, social workers, nurses, medical students, residents, and fellows. The Banner Alzheimer's Institute located in Phoenix, Arizona, has an unusually ambitious mission: to end Alzheimer's disease without losing a generation, set a new standard of care for patients and families, and forge a model of collaboration in biomedical research. The Institute provides high-level care and treatment for patients affected by Alzheimer's disease, dementia, and related disorders. In addition, the Institute offers extensive support services for families and many unique and rewarding research opportunities.

Clinical Management of Episodic Memory Changes in Dementia.

PURPOSE OF REVIEW: The purpose of this review was to discuss therapeutic options available for the treatment of memory difficulties in dementia. RECENT FINDINGS: Because of the lack of progress in the availability of new medications, there has been an increased interest in focusing on non-pharmacological means to management cognitive symptoms related to dementia. The clinical management of memory loss should focus both on pharmacological and non-pharmacological approaches. Treatment with medications should usually begin with a cholinesterase inhibitor and then followed by addition of memantine if there is a decline. In addition to medication management, emphasis should be placed on the importance of maintaining a healthy lifestyle that encompasses physical activities, cognitive stimulation, and a healthy diet.

Observation of social behavior in frontotemporal dementia.

BACKGROUND: The most characteristic manifestations of behavioral variant frontotemporal dementia (bvFTD) are abnormalities in social behavior. However, distinguishing bvFTD based on social behavior can be difficult in structured clinical settings. METHODS: Using a Social Observation Inventory, 10 patients with bvFTD and 10 patients with Alzheimer's disease (AD) were compared to their caregiver interlocutors on 1-hour mealtime, in-home videotaped segments. RESULTS: Compared to caregivers and patients with AD, patients with bvFTD were significantly disturbed in social behavior. In contrast, patients with AD were indistinguishable from their caregivers. The lack of "you" comments and decreased tact and manners distinguished 92.6% of the patients with bvFTD from patients with AD and caregivers. The Social Observation Inventory scores correlated with scores on frontal-executive tests and socioemotional scales. CONCLUSIONS: The systematic observation of social behavior during routine activities may be one of the best ways to distinguish patients with bvFTD from normal individuals and from patients with other dementias.

Interrater reliability of the new criteria for behavioral variant frontotemporal dementia.

OBJECTIVE: To evaluate the interrater reliability of the new International Behavioural Variant FTD Criteria Consortium (FTDC) criteria for behavioral variant frontotemporal dementia (bvFTD). METHODS: Twenty standardized clinical case modules were developed for patients with a range of neurodegenerative diagnoses, including bvFTD, primary progressive aphasia (nonfluent, semantic, and logopenic variant), Alzheimer disease, and Lewy body dementia. Eighteen blinded raters reviewed the modules and 1) rated the presence or absence of core diagnostic features for the FTDC criteria, and 2) provided an overall diagnostic rating. Interrater reliability was determined by κ statistics for multiple raters with categorical ratings. RESULTS: The mean κ value for diagnostic agreement was 0.81 for possible bvFTD and 0.82 for probable bvFTD ("almost perfect agreement"). Interrater reliability for 4 of the 6 core features had "substantial" agreement (behavioral disinhibition, perseverative/compulsive, sympathy/empathy, hyperorality; κ = 0.61-0.80), whereas 2 had "moderate" agreement (apathy/inertia, neuropsychological; κ = 0.41-0.6). Clinician years of experience did not significantly influence rater accuracy. CONCLUSIONS: The FTDC criteria show promise for improving the diagnostic accuracy and reliability of clinicians and researchers. As disease-altering therapies are developed, accurate differential diagnosis between bvFTD and other neurodegenerative diseases will become increasingly important.

False reports from patients with frontotemporal dementia: delusions or confabulations?

Patients with behavioral variant frontotemporal dementia (bvFTD) can make false statements consistent with delusions or confabulations. It is unclear whether bvFTD is primarily associated with either delusions or with confabulations and whether they can be explained by the pathophysiology of this disease. In order to clarify this, we retrospectively surveyed the records of 48 patients with bvFTD for the presence of any false reports and identified four patients. Their false reports included continued interaction with a favorite but dead relation, fictitious marriages with movie stars, and two who claimed that their partner was having an affair. When confronted with the falsity of their statements, the patients conveyed a lack of certainty regarding their external or internal source but persisted in the constancy of their reports. On functional neuroimaging, the patients had predominant frontal involvement. This report found that patients with bvFTD can have both fantastic, wish fulfilling confabulations and typical content-specific delusions. We propose that both phenomena result from known disturbances of ventromedial prefrontal cortex in bvFTD, including deficits in source monitoring and in activating an automatic "doubt tag" for false reports.

Posterior cortical atrophy: evidence for discrete syndromes of early-onset Alzheimer's disease.

BACKGROUND: Posterior cortical atrophy (PCA) may represent a discrete syndrome of Alzheimer's disease (AD) rather than amnestic AD with visual deficits. METHODS: We separated 30 patients with PCA based on ventral and dorsal visual symptoms using cluster analysis and analyzed the demographic, cognitive, and functional imaging features. RESULTS: This analysis revealed subgroups of 26 dorsal and 4 ventral patients. The ventral subgroup had greater confrontational naming impairment, and the dorsal subgroup had greater hypofunction in the parietal regions. The PCA cohort had memory retrieval rather than encoding deficits, and clinical follow-up showed relative isolation of dorsal and ventral visual manifestations. CONCLUSION: These results support 2, mostly nonoverlapping syndromes in patients with PCA, with the commonest affecting the dorsal visual pathway; moreover, the memory retrieval difficulty in the patients with PCA was dissimilar to the amnestic pattern in typical AD. These results suggest that, in most cases, PCA syndromes are discrete clinical variants of AD.

Extrapyramidal signs in the primary progressive aphasias.

BACKGROUND: Extrapyramidal signs (EPS) may vary across 3 major subtypes of primary progressive aphasia (PPA): progressive nonfluent aphasia (PNFA), semantic dementia (SD), and progressive logopenic aphasia (PLA). METHODS: We reviewed initial neurological examinations from a clinical PPA cohort (PNFA = 49, SD = 26, PLA = 28) to determine the prevalence of specific categories of EPS. RESULTS: The presence of any EPS was more common in PNFA (38.8%) and PLA (35.7%) than in SD (3.8%). The PNFA group exhibited the highest prevalence of bradykinesia (PNFA: 22.4%, SD: 3.8%, PLA: 0.0%) and rigidity (PNFA: 30.6%, SD: 0.0%, PLA: 10.7%). Calculated positive likelihood ratios indicated bradykinesia (12.1) or rigidity (5.5) was more strongly associated with PNFA than other PPAs. CONCLUSION: These findings suggest that on initial presentation, specific EPS may help distinguish PPA subtypes when linguistic and/or neuroimaging profiles are indistinct. Moreover, EPS could represent a marker of underlying tauopathy, linking clinical presentation to neuropathology in PPA.

Interhemispheric differences in knowledge of animals among patients with semantic dementia.

OBJECTIVE: To investigate interhemispheric differences on naming and fluency tasks for living versus nonliving things among patients with semantic dementia (SD). BACKGROUND: In SD, left-temporal involvement impairs language and word comprehension, and right-temporal involvement impairs facial recognition. There may be other interhemispheric differences, particularly in the animate-inanimate dichotomy. METHOD: On the basis of magnetic resonance imaging (MRI) ratings of anterior temporal atrophy, 36 patients who met criteria for SD were divided into 21 with left-predominant and 11 with right-predominant involvement (4 others were too symmetric for analysis). The left and right-predominant groups were compared on naming, fluency, and facial recognition tests. RESULTS: Consistent with greater language impairment, the left-predominant patients had worse naming, especially inanimate and letter fluency, than the right-predominant patients. In contrast, difference in scores suggested selective impairment of animal naming, animal name fluency, and semantic knowledge for animate items among the right-predominant patients. Proportionally more right than left-predominant patients misnamed animal items and faces. CONCLUSIONS: These findings support interhemispheric differences in animal knowledge. Whereas left-predominant SD equally affects animate and inanimate words from language involvement, right-predominant SD, with greater sparing of language, continues to impair other semantic aspects of animals. The right anterior temporal region seems to make a unique contribution to knowledge of living things.