Differentiating the Frontal Presentation of Alzheimer's Disease with FDG-PET
Authors: Woodward, Michael C. | Rowe, Christopher C. | Jones, Gareth | Villemagne, Victor L. | Varos, Tammie A.
Article Type: Research Article
Abstract: Background: Alzheimer's disease (AD) can present with behavioral changes with this syndrome described as frontal variant AD (FvAD). Excess frontal pathology may explain this presentation. Neuroimaging with fluoro-deoxy-glucose positron emission tomography (FDG- PET) can be used to examine the effects of pathology in FvAD. Methods: We administered an assessment scale for frontal behavioral impairment, the Frontal Behavioral Inventory (FBI), to 53 patients with AD. Scores in the top quartile were defined as FvAD. FDG- PET was analyzed in 8 frontal regions. Results: The Z (SD) score for metabolism was significantly higher (indicating greater hypometabolism) in the FvAD group than the …remaining AD group for combined left and right orbitofrontal regions (2.64 (SD 0.99) versus 2.11 (1.22), p < 0.03)) and combined left and right medial frontal regions (2.38 (0.63) versus 1.82 (0.88) p < 0.003) but insignificantly different in combined lateral frontal and superior frontal regions. Statistical parametric mapping revealed these frontal regions to be the only brain regions with significantly different metabolism between the FvAD and the remainder of the AD groups. Conclusions: Medial and orbital frontal hypometabolism is greater in AD patients presenting with more frontal/behavioral features, likely reflecting a greater pathological load in these brain regions in FvAD patients. These frontal regions may be more linked to behavioral features than other frontal brain regions. Show more
Keywords: Alzheimer's disease, behavioral features versus hypometabolism, degree of hypometabolism, Frontal Behavioral Inventory, frontal variant Alzheimer's disease, FDG- PET, statistical parametric mapping
DOI: 10.3233/JAD-141110
Citation: Journal of Alzheimer's Disease, vol. 44, no. 1, pp. 233-242, 2015
Potentially Inappropriate Medication, Anticholinergic Burden, and Mortality in People Attending Memory Clinics
Authors: Cross, Amanda J. | George, Johnson | Woodward, Michael C. | Ames, David | Brodaty, Henry | Wolfe, Rory | Connors, Michael H. | Elliott, Rohan A.
Article Type: Research Article
Abstract: Background: There is limited evidence regarding the association between potentially inappropriate medications (PIM) and mortality in older people with cognitive impairment. Objective: To examine whether use of medications considered to be potentially inappropriate in older people with cognitive impairment (PIMcog) and anticholinergic cognitive burden (ACB) were associated with mortality in people who attended memory clinics. Methods: Cross-sectional and longitudinal analyses of data from the Prospective Research In MEmory clinics (PRIME) study. Participants were community-dwelling people who attended nine memory clinics and had a diagnosis of mild cognitive impairment or dementia. PIMcog was defined as any medication considered potentially inappropriate for …a person with cognitive impairment according to Beers or STOPP criteria. Anticholinergic burden was calculated using the ACB scale. Time-dependent Cox-proportional hazards regression was used to analyze associations between PIMcog use/ACB score and all-cause mortality over a three-year follow-up period. The regression model included the baseline variables: age, gender, education, cognitive diagnoses, total number of medications, disease-burden, cognition, physical function, and neuropsychiatric symptoms. Results: Of 964 participants, 360 (37.3%) used one or more PIMcog at some time during the study; most commonly anticholinergics and sedatives. 624 (64.7%) participants used a medication with potential or definite anticholinergic properties (ACB>0) at some point during the study. Both PIMcog use (adjusted hazard ratio: 1.42 95% CI: 1.12–1.80) and ACB score (adjusted hazard ratio: 1.18 95% CI: 1.06–1.32) were associated with mortality. Conclusion: Use of PIMcogs and medications with anticholinergic properties was common among memory clinic patients and both were associated with mortality. Show more
Keywords: Alzheimer’s disease, cholinergic antagonists, cognitive dysfunction, dementia, inappropriate prescribing, mortality, potentially inappropriate medication list, contstartabstract
DOI: 10.3233/JAD-170265
Citation: Journal of Alzheimer's Disease, vol. 60, no. 2, pp. 349-358, 2017
Among Vitamin B12 Deficient Older People, High Folate Levels are Associated with Worse Cognitive Function: Combined Data from Three Cohorts
Authors: Moore, Eileen M. | Ames, David | Mander, Alastair G. | Carne, Ross P. | Brodaty, Henry | Woodward, Michael C. | Boundy, Karyn | Ellis, Kathryn A. | Bush, Ashley I. | Faux, Noel G. | Martins, Ralph N. | Masters, Colin L. | Rowe, Christopher C. | Szoeke, Cassandra | Watters, David A.
Article Type: Research Article
Abstract: Background: Folate fortification of food aims to reduce the number of babies born with neural tube defects, but has been associated with cognitive impairment when vitamin B12 levels are deficient. Given the prevalence of low vitamin B12 levels among the elderly, and the global deployment of food fortification programs, investigation of the associations between cognitive impairment, vitamin B12, and folate are needed. Objective: To investigate the associations of serum vitamin B12, red cell folate, and cognitive impairment. Methods: Data were collected on 1,354 subjects in two studies investigating cognitive impairment, and from patients attending for assessment or management of memory …problems in the Barwon region of south eastern Australia between 2001 and 2011. Eligible subjects who had blood measurements of vitamin B12 and red cell folate taken within six months of cognitive testing were included. Subjects with stroke or neurodegenerative diseases other than Alzheimer’s disease were excluded. A Mini-Mental State Examination score of <24 was used to define impaired cognitive function. Results: Participants with low serum vitamin B12 (<250 pmol/L) and high red cell folate (>1,594 nmol/L) levels were more likely to have impaired cognitive performance (adjusted odds ratio (AOR) 3.45, 95% confidence interval (CI): 1.60–7.43, p = 0.002) when compared to participants with biochemical measurements that were within the normal ranges. Participants with high folate levels, but normal serum vitamin B12, were also more likely to have impaired cognitive performance (AOR 1.74, 95% CI: 1.03–2.95, p = 0.04). Conclusions: High folate or folic acid supplements may be detrimental to cognition in older people with low vitamin B12 levels. This topic is of global significance due to the wide distribution of food fortification programs, so prospective studies should be a high priority. Show more
Keywords: Aged, Alzheimer's disease, cognition, folic acid, vitamin B12
DOI: 10.3233/JAD-131265
Citation: Journal of Alzheimer's Disease, vol. 39, no. 3, pp. 661-668, 2014