Steven Z. Chao

Recruitment of Chinese American Elders into Dementia Research: The UCSF ADRC Experience

PURPOSE To describe the results of efforts to recruit Asian Americans into longitudinal research on cognitive decline in aging. DESIGN AND METHODS Recruitment strategies include clinics for assessment of cognitive impairment at the University of California, San Francisco campus and San Franciscos Chinatown, lectures to local health care providers and community members, participation in community events, and publications in mass media. RESULTS Over 200 Chinese patients were evaluated in our outreach clinic. Many were primarily Chinese speaking with low levels of education. One hundred and twenty-five participants enrolled, and annual follow-up has been 88%. Among enrollees, 36% were recruited from our clinical service; 30% via word of mouth; and the rest from community lectures and events, flyers, and mass media. Participants who enrolled were relatively highly educated, tended to be interested in learning about their cognitive abilities, and were supportive of the goals of research. IMPLICATIONS Despite the significant cultural and linguistic barriers, Chinese Americans can be successfully recruited into longitudinal studies of aging and cognitive impairment. Clinical services are a critical component of such an effort, and low education and other factors that may be associated with it are clear barriers to research participation.

Schizophrenia or Neurodegenerative Disease Prodrome? Outcome of a First Psychotic Episode in a 35-Year-Old Woman

NIH Public Access Author Manuscript Psychosomatics. Author manuscript; available in PMC 2013 May 22. NIH-PA Author Manuscript Published in final edited form as: Psychosomatics. 2012 May ; 53(3): 280–284. doi:10.1016/j.psym.2011.04.005. Schizophrenia or neurodegenerative disease prodrome? Outcome of a first psychotic episode in a 35-year old woman Baber K. Khan, B.A., University of California San Francisco, Memory and Aging Center, Department of Neurology, 350 Parnassus Avenue, San Francisco, CA 94143. Josh D. Woolley, MD/PhD, University of California San Francisco, Langley Porter, Department of Psychiatry, 401 Parnassus Avenue, Room 159, San Francisco, CA 94143. Steven Chao, MD/PhD, University of California San Francisco, Memory and Aging Center, Department of Neurology, 350 Parnassus Avenue, San Francisco, CA 94143. NIH-PA Author Manuscript Tricia See, ScM, University of California San Francisco, Memory and Aging Center, Department of Neurology, 350 Parnassus Avenue, San Francisco, CA 94143. Anna M. Karydas, B.A., University of California San Francisco, Memory and Aging Center, Department of Neurology, 350 Parnassus Avenue, San Francisco, CA 94143. Bruce L. Miller, MD, and University of California San Francisco, Memory and Aging Center, Department of Neurology, 350 Parnassus Avenue, San Francisco, CA 94143. Katherine P. Rankin, PhD University of California San Francisco, Memory and Aging Center, Department of Neurology, 350 Parnassus Avenue, San Francisco, CA 94143. Abstract NIH-PA Author Manuscript Background—Patients with early onset neurodegenerative disease can present with a clinical syndrome that overlaps with schizophrenia, and it is not uncommon for these patients to undergo long-term care in psychiatric settings rather than receiving more appropriate care by neurologists specializing in their disease. Case report—A 35-year old woman who presented with new-onset delusions, eating abnormalities, disorganized behavior, lack of insight, disinhibition, and stereotypical motor behaviors was diagnosed with schizophrenia and institutionalized. Later she was found to have a

Depressive symptoms in Chinese-American subjects with cognitive impairment

OBJECTIVES To compare the prevalence of depressive symptoms and frequency of antidepressant use between a group of elderly Chinese-American subjects with and without cognitive impairment and a group of matched white subjects. A secondary aim was to examine the clinical and demographic predictors of depressive symptoms across these groups. METHODS The study was conducted at an academic neurology subspecialty clinic. This was a case-control study with 140 Chinese-American subjects and 140 demographically and cognitively matched white subjects. In each group, there were 48 cognitively normal and 92 cognitively impaired participants (49 with mild cognitive impairment, 43 with Alzheimer disease). The proportion of individuals with significant depressive symptoms, as indicated by a Geriatric Depression Scale score ≥6 of 15, and frequency of antidepressant use were compared across groups by using χ(2) analysis. Factors predicting depressive symptoms, including racial and diagnostic group, age, gender, Mini-Mental State Examination score, level of functional impairment, education level, and medical comorbidities, were assessed by using linear regression analysis. RESULTS Significant depressive symptoms were more common in cognitively impaired Chinese-American (35%) than cognitively impaired white (15%; χ(2)[1] = 9.4; p = 0.004) subjects. Chinese-American subjects with cognitive impairment were less likely to be receiving treatment for depression (12%) than white subjects with cognitive impairment (37%; χ(2)[1] = 15.6; p = 0.002). Racial and diagnostic group, age, level of functional impairment, Mini-Mental State Examination score, and education level were all statistically significant independent predictors of Geriatric Depression Scale score. CONCLUSIONS Elderly Chinese-American subjects with cognitive impairment are at increased risk for unrecognized and untreated depressive symptoms compared with elderly white subjects with cognitive impairment. Education level may contribute to this risk or it may be a surrogate marker for other factors contributing to depressive symptoms in this group.

Sedation mediates part of Citalopram's effect on agitation in Alzheimer's disease

BACKGROUND We found a benefit of citalopram for agitation in the Citalopram for Agitation in Alzheimers Disease study (CitAD), and wondered if this was mediated by a sedative effect. CitAD was a randomized, placebo-controlled, double-blind, parallel group trial conducted at 8 academic centers in the United States and Canada from August 2009 to January 2013. One hundred sixty-two participants with probable Alzheimers disease (AD) and clinically significant agitation were analyzed in this study. Participants received a psychosocial intervention and were randomized to receive either citalopram or placebo (approximately half assigned to each group). Participants were rated on the Neurobehavioral Rating Scale Agitation subscale and measures of sedation (i.e., fatigue and somnolence). METHODS Using the MacArthur Foundation procedures for documenting a mediator effect, we performed a secondary analysis examining whether sedation mediates the effect of treatment on agitation outcome. RESULTS We found a statistically significant mediating effect of sedation on agitation outcomes, but the magnitude of the effect was small, only explaining 11% of the variance in agitation, with a significant, but modest effect size of 0.16 (95% CI: 0.08 to 0.22). CONCLUSIONS The benefit of citalopram was partly due to sedation but largely due to other mechanisms of action.

Apolipoprotein ε4 is associated with lower brain volume in cognitively normal Chinese but not white older adults.

Studying ethnically diverse groups is important for furthering our understanding of biological mechanisms of disease that may vary across human populations. The ε4 allele of apolipoprotein E (APOE ε4) is a well-established risk factor for Alzheimer’s disease (AD), and may confer anatomic and functional effects years before clinical signs of cognitive decline are observed. The allele frequency of APOE ε4 varies both across and within populations, and the size of the effect it confers for dementia risk may be affected by other factors. Our objective was to investigate the role APOE ε4 plays in moderating brain volume in cognitively normal Chinese older adults, compared to older white Americans. We hypothesized that carrying APOE ε4 would be associated with reduced brain volume and that the magnitude of this effect would be different between ethnic groups. We performed whole brain analysis of structural MRIs from Chinese living in America (n = 41) and Shanghai (n = 30) and compared them to white Americans (n = 71). We found a significant interaction effect of carrying APOE ε4 and being Chinese. The APOE ε4xChinese interaction was associated with lower volume in bilateral cuneus and left middle frontal gyrus (Puncorrected<0.001), with suggestive findings in right entorhinal cortex and left hippocampus (Puncorrected<0.01), all regions that are associated with neurodegeneration in AD. After correction for multiple testing, the left cuneus remained significantly associated with the interaction effect (PFWE = 0.05). Our study suggests there is a differential effect of APOE ε4 on brain volume in Chinese versus white cognitively normal elderly adults. This represents a novel finding that, if verified in larger studies, has implications for how biological, environmental and/or lifestyle factors may modify APOE ε4 effects on the brain in diverse populations.

The Chinese Verbal Learning Test specifically assesses hippocampal state.

Background: Recently, the Chinese Verbal Learning Test (ChVLT) was developed to assess episodic memory in Chinese speakers. The goal of this analysis was to determine whether memory consolidation as measured by the ChVLT was specifically associated with hippocampal volume in patients with cognitive impairment. Methods: We administered the ChVLT to 22 Chinese-speaking patients with mild cognitive impairment and 9 patients with dementia and obtained hippocampal and cortical volumes from T1-weighted magnetic resonance imaging. Results: Linear regression revealed that hippocampal volume explained 9.9% of the variance in delayed memory (P = .018) after controlling for the effects of age, education, immediate recall after the last learning trial, overall level of cognitive impairment, and volumes of other cortical regions. conclusion: These results indicate that the ChVLT is specifically correlated with hippocampal volume, supporting its utility for detecting hippocampal disease and monitoring hippocampal state over time.

Assessment of PET & ASL metabolism in the hippocampal subfields of MCI and AD using simultaneous PET-MR.

Alzheimer’s disease (AD) has been reported to show decreased metabolic activity in the hippocampus using FDG PET-MR. Histological data suggests that the hippocampal subfields are selectively affected in AD. Given the simultaneous imaging nature of integrated PET-MR scanners and the multimodal capabilities of PET-MR, our purpose here is to assess FDG activity, as well as ASL perfusion in the subfields of MCI and AD patients. 10 consecutive subjects were recruited for this study 3 MCI, 3 AD patients and 4 age-matched controls. The scanning was performed on a simultaneous 3T PET/MR scanner. To delineate the hippocampal subfields, automatic segmentation of hippocampal subfields (ASHS) was employed. Static FDG-PET series were reconstructed for analysis at 45-75 min for all subjects. All imaging sequences were automatically registered to the oblique coronal T2-weighted images (segmentation space). PET standardized uptake values (SUV) in the hippocampal subfields were normalized by the pons. FDG PET metabolism was reduced significantly in AD, as well as MCI patients as compared to controls, with the highest effect demonstrated in the CA3/DG and CA1/2 (p = 0.047, subfields. Patients (MCI and AD combined) had decreased metabolism as compared to controls in CA1/2 and significantly smaller volumes the Subiculum. When assessing CBF across groups, a significant decrease in CBF was found in the Subiculum. Our preliminary results demonstrate that PET-MRI may potentially be a sensitive biomarker and tool for early diagnosis of AD. They also confirm the importance of assessing metabolic and structural changes of neurodegenerative diseases at the subfield level.

Correlation between arterial spin labeling MRI and dynamic FDG on PET-MR in Alzheimer’s disease and non-Alzhiemer’s disease patients

Regional hypoperfusion on Arterial Spin Labeling (ASL) MRI and corresponding regions of hypometabolism on FDG PET have been reported in Alzheimer’s Disease (AD). To our knowledge these correlations have not been studied under simultaneous acquisition. The purpose of this study is to investigate the correlation of ASL with FDG PET under simultaneous acquisition on PET-MR and to explore this correlation as a possible biomarker for AD. Dynamic FDG and ASL imaging was performed using a simultaneous TOF-enabled PET-MR scanner in 7 subjects without AD and 3 subjects with AD. Average age was 68±5 years. Automated atlas-based segmentation was performed using T2 MRI using the Talairach atlas. Quantitative analysis of ASL and FDG (delayed 45-75 minute scan) was performed in five regions using the pons as a reference region for both perfusion and metabolism. Statistical analyses included Spearman’s correlation and student’s t-test. Significant correlation of relative perfusion and metabolism was found in two of the five brain regions including the putamen (p = 0.018) and the hippocampus (p = 0.031). In addition, there was significant difference between the relative perfusion and metabolism of the thalamus (p = 0.04). No difference was seen between the AD and non-AD groups. Simultaneous PET-MR demonstrates a positive correlation of perfusion of ASL with metabolism on FDG PET in the hippocampus and putamen. The putamen correlation has previously been reported in the literature on a non-simultaneous ASL and FDG imaging. The thalamus was noted to have a difference in the relative perfusion and metabolism representing a perfusion-metabolism mismatch. Future studies should explore the correlation in additional brain regions and the meaning of perfusion-metabolism mismatches as potential imaging biomarkers for patients with and without AD.

Frontotemporal dementia in eight Chinese individuals.

Frontotemporal dementia (FTD) has rarely been reported in Chinese populations. There are many potential reasons for this, including possible hesitancy on the part of patients or families to bring FTD-related symptoms to medical attention. Here, we present data on eight Chinese individuals, all of whom met criteria for the behavioral variant of FTD or the semantic variant of primary progressive aphasia. These patients presented for neurological evaluation at a relatively advanced stage. The mean MMSE score at initial presentation was 15. Behavioral symptoms were common and usually elicited during the medical history only after direct questioning. Delay in presentation was attributed to a variety of issues, including family disagreements about whether the symptoms represented a disease and lack of medical insurance. These cases illustrate that the symptoms of FTD in Chinese-Americans are similar to those in Caucasians but various factors, some potentially culturally relevant, may influence the likelihood and timing of clinical presentation for FTD, as well as other dementias. Additional study of FTD in diverse ethnic groups needs to address barriers to clinical presentation, including factors that may be culturally specific.