Psychiatry - Research Publications

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    Decline in Cognitive Function over 18 Months in Healthy Older Adults with High Amyloid-β
    Ellis, KA ; Lim, YY ; Harrington, K ; Ames, D ; Bush, AI ; Darby, D ; Martins, RN ; Masters, CL ; Rowe, CC ; Savage, G ; Szoeke, C ; Villemagne, VL ; Maruff, P (IOS PRESS, 2013)
    We aimed to characterize the nature and magnitude of cognitive decline in a group of healthy older adults with high and low levels of amyloid-β (Aβ) and who were APOE ε4 carriers and non-carriers. Healthy older adults underwent positron emission tomography neuroimaging for Aβ, APOE genotyping, and cognitive and clinical assessment as part of their baseline assessment in the Australian Imaging, Biomarker, and Lifestyle study. Cognitive function and clinical ratings were reassessed 18 months later. Linear mixed model analyses adjusted for baseline cognitive function indicated that relative to healthy older adults with low Aβ, healthy older adults with high Aβ showed greater decline in episodic memory and language at 18 months. No decline on any measure of executive function, attention, or clinical rating was observed for healthy older adults with high Aβ levels. Compared to non-carriers, APOE ε4 carriers showed a greater decline only on the task of visual memory at the 18 month assessment. Importantly though, no interaction between APOE ε4 and Aβ was observed on any measure of cognitive function. The results of this study suggest that high Aβ load was associated with greater decline in episodic memory and language, that the magnitude of this decline was moderate and equivalent across both domains, and that APOE ε4 carriage did not moderate the relationship between Aβ and decline in memory and language functions.
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    Increased Risk of Cognitive Impairment in Patients With Diabetes Is Associated With Metformin
    Moore, EM ; Mander, AG ; Ames, D ; Kotowicz, MA ; Carne, RP ; Brodaty, H ; Woodward, M ; Boundy, K ; Ellis, KA ; Bush, AI ; Faux, NG ; Martins, R ; Szoeke, C ; Rowe, C ; Watters, DA (AMER DIABETES ASSOC, 2013-10)
    OBJECTIVE: To investigate the associations of metformin, serum vitamin B12, calcium supplements, and cognitive impairment in patients with diabetes. RESEARCH DESIGN AND METHODS: Participants were recruited from the Primary Research in Memory (PRIME) clinics study, the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging, and the Barwon region of southeastern Australia. Patients with Alzheimer disease (AD) (n=480) or mild cognitive impairment (n=187) and those who were cognitively intact (n=687) were included; patients with stroke or with neurodegenerative diseases other than AD were excluded. Subgroup analyses were performed for participants who had either type 2 diabetes (n=104) or impaired glucose tolerance (n=22). RESULTS: Participants with diabetes (n=126) had worse cognitive performance than participants who did not have diabetes (n=1,228; adjusted odds ratio 1.51 [95% CI 1.03-2.21]). Among participants with diabetes, worse cognitive performance was associated with metformin use (2.23 [1.05-4.75]). After adjusting for age, sex, level of education, history of depression, serum vitamin B12, and metformin use, participants with diabetes who were taking calcium supplements had better cognitive performance (0.41 [0.19-0.92]). CONCLUSIONS: Metformin use was associated with impaired cognitive performance. Vitamin B12 and calcium supplements may alleviate metformin-induced vitamin B12 deficiency and were associated with better cognitive outcomes. Prospective trials are warranted to assess the beneficial effects of vitamin B12 and calcium use on cognition in older people with diabetes who are taking metformin.
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    Rapid Decline in Episodic Memory in Healthy Older Adults with High Amyloid-β
    Lim, YY ; Pietrzak, RH ; Ellis, KA ; Jaeger, J ; Harrington, K ; Ashwood, T ; Szoeke, C ; Martins, RN ; Bush, AI ; Masters, CL ; Rowe, CC ; Villemagne, VL ; Ames, D ; Darby, D ; Maruff, P (IOS PRESS, 2013)
    High levels of amyloid-β (Aβ) have been associated with greater rates of decline in episodic memory over 18 months in healthy older adults. Serial assessments over shorter time intervals may facilitate earlier detection of Aβ-related memory decline in healthy older adults. In forty-four healthy older adults enrolled in the Australian Imaging, Biomarkers and Lifestyle Rate of Change Sub-Study, we compared rates of change in cognition over six months in healthy older adults with high and low levels of Aβ. High Aβ was associated with greater decline in episodic memory measures over 6 months in healthy older adults.
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    Clinical utility of the cogstate brief battery in identifying cognitive impairment in mild cognitive impairment and Alzheimer's disease.
    Maruff, P ; Lim, YY ; Darby, D ; Ellis, KA ; Pietrzak, RH ; Snyder, PJ ; Bush, AI ; Szoeke, C ; Schembri, A ; Ames, D ; Masters, CL (BioMed Central, 2013-12-23)
    Background: Previous studies have demonstrated the utility and sensitivity of the CogState Brief Battery (CBB) in detecting cognitive impairment in Alzheimer's disease (AD) and mild cognitive impairment (MCI) and in assessing cognitive changes in the preclinical stages of AD. Thus, the CBB may be a useful screening tool to assist in the management of cognitive function in clinical settings. In this study, we aimed to determine the utility of the CBB in identifying the nature and magnitude of cognitive impairments in MCI and AD.; Methods: Healthy adults (n = 653) adults with amnestic MCI (n = 107), and adults with AD (n = 44) who completed the CBB participated in this study. Composite Psychomotor/Attention and Learning/Working Memory scores were computed from the individual CBB tests. Differences in composite scores were then examined between the three groups; and sensitivity and specificity analyses were conducted to determine cut scores for the composite scores that were optimal in identifying MCI- and AD-related cognitive impairment.; Results: Large magnitude impairments in MCI (g = 2.2) and AD (g = 3.3) were identified for the learning/working memory composite, and smaller impairments were observed for the attention/psychomotor composite (g's = 0.5 and 1, respectively). The cut-score associated with optimal sensitivity and specificity in identifying MCI-related cognitive impairment on the learning/working memory composite was -1SD, and in the AD group, this optimal value was -1.7SD. Both composite scores showed high test-retest reliability (r = 0.95) over four months. Poorer performance on the memory composite was also associated with worse performance on the Mini Mental State Exam and increasing severity on the Clinical Dementia Rating Scale sum of boxes score.; Conclusions: Results of this study suggest that the CogState learning/working memory composite score is reduced significantly in CI and AD, correlate well with measures of disease classification and are useful in identifying memory impairment related to MCI- and AD.;