Linda Mah

Anxiety Symptoms in Amnestic Mild Cognitive Impairment Are Associated with Medial Temporal Atrophy and Predict Conversion to Alzheimer Disease

OBJECTIVE To test the hypothesis that anxiety in amnestic mild cognitive impairment (aMCI) increases rates of conversion to Alzheimer disease (AD) and to identify potential neural mechanisms underlying such an association. METHODS Participants (N = 376) with aMCI from the Alzheimers Disease Neuroimaging Initiative (ADNI) were studied over a median period of 36 months. A Cox proportional-hazards model was used to assess the association between anxiety severity ratings on the Neuropsychiatric Inventory Questionnaire and AD risk. Other variables were depression, memory loss, and MRI-derived AD-related regions of interest (ROIs), including hippocampal, amygdalar, entorhinal cortical (EC) volumes, and EC thickness, In addition, a linear regression model was used to determine the effect of anxiety in aMCI on rates of atrophy within ROIs. RESULTS Anxiety severity increased rate of aMCI conversion to AD, after controlling for depression and cognitive decline. The association between anxiety and AD remained significant even with inclusion of ROI baseline values or atrophy rates as explanatory variables. Further, anxiety status predicted greater rates of decrease in EC volume. An association between anxiety and EC thickness missed significance. CONCLUSION Anxiety symptoms in aMCI predict conversion to AD, over and beyond the effects of depression, memory loss, or atrophy within AD neuroimaging biomarkers. These findings, together with the greater EC atrophy rate predicted by anxiety, are compatible with the hypothesis that anxiety is not a prodromal noncognitive feature of AD but may accelerate decline toward AD through direct or indirect effects on EC.

Dynamic working memory performance in individuals with single-domain amnestic mild cognitive impairment

Previous studies have observed poorer working memory performance in individuals with amnestic mild cognitive impairment than in healthy older adults. It is unclear, however, whether these difficulties are true only of the multiple-domain clinical subtype in whom poorer executive functioning is common. The current study examined working memory, as measured by the self-ordered pointing task (SOPT) and an n-back task, in healthy older adults and adults with single-domain amnestic mild cognitive impairment (aMCI). Individuals with single-domain aMCI committed more errors and required longer to develop an organizational strategy on the SOPT. The single-domain aMCI group did not differ from healthy older adults on the 1-back or 2-back, but had poorer discrimination on the 3-back task. This is, to our knowledge, the first characterization of dynamic working memory performance in a single-domain aMCI group. These results lend support for the idea that clinical amnestic MCI subtypes may reflect different stages on a continuum of progression to dementia and question whether standardized measures of working memory (span tasks) are sensitive enough to capture subtle changes in performance.

ASSOCIATION BETWEEN SLEEP DISTURBANCE AND MEDIAL TEMPORAL LOBE STRUCTURES IN MILD COGNITIVE IMPAIRMENT

in CN than inMCI (Figure 1b). Amodel includingWMH andmetaROI thickness significantly predicted cognitive status (adj. R21⁄4 .118, p1⁄4 .0001); both WMH volume and meta-ROI thickness were significant predictors (Table 2). WMH volumes by cognitive status and median-split thickness are shown in Figure 2. Age, APOE34 status and sex were not significant. All component regional model R2 values were lower than the meta-ROI model R2, with entorhinal cortex the best component region (R21⁄4 .117). Conclusions: In a community-dwelling older adult cohort, markers of CVD (WMH volume) and AD-specific neurodegeneration (meta-ROI thickness) independently predict cognitive status. Age does not substantially modify these relations. The AD-specific meta-ROI outperforms component regional thickness measures. These results suggest complex interactions exist between CVD, neurodegeneration and cognitive diagnosis in late life.

ALTERATIONS IN EMOTIONAL VERBAL MEMORY IN SUBJECTIVE COGNITIVE DECLINE AND AMNESTIC MILD COGNITIVE IMPAIRMENT

progression to Alzheimer’s disease (AD)-type dementia. It remains uncertain in which stage these factors have an influence and how they are associated with AD biomarkers. Therefore, we investigated how risk factors are associated with AD biomarkers in cerebrospinal fluid (CSF) and whether they influence cognitive decline in preclinical AD. Methods:We selected 438 participants from the longitudinal studies at the Knight Alzheimer’s Disease Research Center (mean age: 68.3, SD: 8.5), with a baseline Clinical Dementia Rating (CDR) of 0. All participants had baseline data available for 12 risk factors (Table 1), neuropsychological testing, APOE genotyping and CSF levels of Ab 1-42, tau and p-tau181. We created four groups based on the abnormality of Ab (A +/-) and tau(s) (T +/-) and compared differences in frequency of risk factors among groups using Chi-Square testing. Cognitive decline, with MMSE as outcomes measure, was assessed using linear mixed modeling. All analyses were adjusted for demographics and APOE genotype. Results:The frequencies of risk factors and baseline characteristics for each biomarker group are shown in Table 1. We found a higher frequency of transient ischemic attach (TIA) and a lower frequency of obesity in the T+ groups. Cardiovascular disorders occurred

ALTERATIONS IN BEHAVIOURAL RESPONSES TO EMOTIONAL FACIAL EXPRESSIONS IN SINGLE-DOMAIN AMNESTIC MILD COGNITIVE IMPAIRMENT

P4-351 EVALUATION OF TAU BURDEN IN A CROSSSECTIONALCOHORTOFALZHEIMER’SDISEASE SUBJECTS USING [F]GTP1 (GENENTECH TAU PROBE 1) Sandra Sanabria Bohorquez, Olivier Barret, Gilles Tamagnan, David Alagille, Jan Marik, Gai Ayalon, Thomas Bengtsson, Alex de Crespigny, Danna Jennings, John P. Seibyl, Kenneth Marek, Robby Weimer, Geoffrey A. Kerchner, Genentech, Inc., South San Francicso, CA, USA; Molecular Neuroimaging, LLC, New Haven, CT, USA; 3 Genentech, Inc., South San Francisco, CA, USA. Contact e-mail: sanabris@gene.com