Authors: Harrington, Karra D. | Vasan, Shradha | Kang, Jee eun | Sliwinski, Martin J. | Lim, Michelle H.
Article Type: Systematic Review
Abstract: Background: Loneliness has been highlighted as a risk factor for dementia. However, the nature of the relationship between loneliness and cognitive function prior to onset of dementia is unclear. Objective: The aim of this systematic review and meta-analysis was to examine the relationship between loneliness and cognitive function in samples screened for dementia at study commencement. Methods: Five electronic databases (PubMed, PsycNET, Web of Science, EBSCOhost, Scopus) were searched from inception to August 31, 2021. A narrative review and random-effects meta-analysis were conducted on studies meeting search criteria. PROSPERO registration number: CRD42020155539. Results: The sixteen studies that met inclusion criteria …involved 30,267 individuals, with mean age ranging from 63.0 to 84.9 years. Studies varied in dementia screening criteria, measurement of loneliness and cognitive function, and statistical modeling approach. The narrative review indicated that loneliness was associated with poorer global cognition, episodic memory, working memory, visuospatial function, processing speed, and semantic verbal fluency. Results of the meta-analysis indicated that loneliness was negatively associated with global cognitive function (overall r = –0.08; 95% CI = –0.14, –0.02; n = 6). Due to lack of sufficient data and heterogeneity between studies, we were unable to explore associations with other cognitive domains or longitudinal associations. Conclusion: Loneliness is associated with subtle impairment across multiple cognitive domains in older adults who were screened for dementia. Better characterization of this relationship will provide important information about how loneliness contributes to the clinical and pathological sequalae of AD and be informative for risk reduction and early detection strategies. Show more
Keywords: Alzheimer disease, cognition, dementia, loneliness
DOI: 10.3233/JAD-220832
Citation: Journal of Alzheimer's Disease, vol. 91, no. 4, pp. 1243-1259, 2023
Authors: Lim, Yen Ying | Pietrzak, Robert H. | Ellis, Kathryn A. | Jaeger, Judith | Harrington, Karra | Ashwood, Tim | Szoeke, Cassandra | Martins, Ralph N. | Bush, Ashley I. | Masters, Colin L. | Rowe, Christopher C. | Villemagne, Victor L. | Ames, David | Darby, David | Maruff, Paul
Article Type: Short Communication
Abstract: 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.
Keywords: Alzheimer's disease, amyloid-β, cognitive decline, episodic memory, neuropsychological assessment
DOI: 10.3233/JAD-2012-121516
Citation: Journal of Alzheimer's Disease, vol. 33, no. 3, pp. 675-679, 2013
Authors: Ellis, Kathryn A. | Lim, Yen Ying | Harrington, Karra | Ames, David | Bush, Ashley I. | Darby, David | Martins, Ralph N. | Masters, Colin L. | Rowe, Christopher C. | Savage, Greg | Szoeke, Cassandra | Villemagne, Victor L. | Maruff, Paul | the AIBL Research Group
Article Type: Research Article
Abstract: 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. Show more
Keywords: Alzheimer's disease, amyloid-β, apolipoprotein E ε4, cognitive change, cognitive neuropsychology, healthy older adults
DOI: 10.3233/JAD-122170
Citation: Journal of Alzheimer's Disease, vol. 34, no. 4, pp. 861-871, 2013
Authors: Dang, Christa | Harrington, Karra D. | Lim, Yen Ying | Ames, David | Hassenstab, Jason | Laws, Simon M. | Yassi, Nawaf | Hickey, Martha | Rainey-Smith, Stephanie | Robertson, Joanne | Sohrabi, Hamid R. | Salvado, Olivier | Weinborn, Michael | Villemagne, Victor L. | Rowe, Christopher C. | Masters, Colin L. | Maruff, Paul | for the AIBL Research Group
Article Type: Research Article
Abstract: Background: Preclinical Alzheimer’s disease (AD) is defined by cerebral amyloid-β positivity (Aβ+) in cognitively normal (CN) older adults. Objective: To estimate the risk of progression to the symptomatic stages of AD due to PET Aβ+ and the extent that progression was influenced by other demographic, genetic, and clinical characteristics in a large prospective study. Methods: Fine-Gray subdistribution modeling was used to examine the risk of progression from CN to MCI/dementia due to Aβ+, APOE ɛ 4 carriage, and their interaction in the Australian Imaging, Biomarkers and Lifestyle (AIBL) flagship study of aging CN cohort (n = 599) over 8 years. Results: 17.7% …Aβ+ and 8.1% Aβ–progressed over 8 years (OR: 2.43). Risk of progression for Aβ+ was 65–104% greater than Aβ–. Aβ+ APOE ɛ 4 carriers were at 348% greater risk than all other participants. Significant risk factors of progression in Aβ+ were age (HR: 1.05), PET SUVR (HR: 2.49) and APOE ɛ 4 carriage (HR: 2.63); only age was a significant risk factor in Aβ–(HR: 1.09). Aβ–progressors were not near the threshold for Aβ+. These relationships were not moderated by hypertension, diabetes, obesity, or stroke/TIA. Conclusion: Aβ+ is an important prognostic marker for progression from CN to MCI/dementia in older adults and APOE ɛ 4 carriage provides further predictive value in the presence of Aβ+. These data suggest that Aβ-associated clinical progression is consistent with clinical-pathological models of AD, whereas progression in the absence of elevated Aβ deposition may be the result of neuropathological processes other than AD that accumulate with age. Show more
Keywords: Alzheimer’s disease, APOE ɛ4, biomarkers, dementia, mild cognitive impairment
DOI: 10.3233/JAD-180507
Citation: Journal of Alzheimer's Disease, vol. 65, no. 4, pp. 1313-1325, 2018
Authors: Hollands, Simone | Lim, Yen Ying | Laws, Simon M. | Villemagne, Victor L. | Pietrzak, Robert H. | Harrington, Karra | Porter, Tenielle | Snyder, Peter | Ames, David | Fowler, Christopher | Rainey-Smith, Stephanie R. | Martins, Ralph N. | Salvado, Olivier | Robertson, Joanne | Rowe, Christopher C. | Masters, Colin L. | Maruff, Paul | for the AIBL Research Group
Article Type: Research Article
Abstract: Background: In cognitively normal (CN) older adults, carriage of the apolipoprotein E (APOE ) ɛ 4 allele is associated with increased risk for dementia of the Alzheimer type (AD-dementia). It is unclear whether this occurs solely through APOE ɛ 4 increasing amyloid-β (Aβ) accumulation or through processes independent of Aβ. Objective: To determine the extent and nature to which APOE ɛ 4 increases risk for clinical disease progression in CN older adults. Methods: Data from the total (n = 765) and Aβ-imaged (n = 423) CN cohort in the Australian Imaging, Biomarker and Lifestyle (AIBL) Study of Ageing was analyzed using Cox …proportional hazard models to estimate ɛ 4 risk for clinical disease progression over a 72-month follow-up. Results: With Aβ status unknown and risk from demographic characteristics controlled, ɛ 4 carriage increased risk for clinical disease progression over 72 months by 2.66 times compared to risk of non-ɛ 4 carriage. Re-analysis with Aβ status included showed that abnormally high Aβ increased risk for clinical disease progression over 72 months by 2.11 times compared to risk of low Aβ. However, with Aβ level known, ɛ 4 carriage was no longer predictive of clinical disease progression. Conclusion: In CN older adults, the risk of ɛ 4 for clinical disease progression occurs through the effect of ɛ 4 increasing Aβ levels. Show more
Keywords: Alzheimer’s disease, Alzheimer type dementia, amyloid-β, apolipoprotein E4, positron emission tomography
DOI: 10.3233/JAD-161019
Citation: Journal of Alzheimer's Disease, vol. 57, no. 2, pp. 411-422, 2017
Authors: Gardener, Samantha L. | Rainey-Smith, Stephanie R. | Sohrabi, Hamid R. | Weinborn, Michael | Verdile, Giuseppe | Fernando, W.M.A.D. Binosha | Lim, Yen Ying | Harrington, Karra | Burnham, Samantha | Taddei, Kevin | Masters, Colin L. | Macaulay, Stuart L. | Rowe, Christopher C. | Ames, David | Maruff, Paul | Martins, Ralph N. | for the AIBL Research Group
Article Type: Research Article
Abstract: Evidence suggests that a diet low in carbohydrates can impact on cognitive performance among those with Alzheimer’s disease (AD). However, there is a lack of data assessing this relationship among cognitively normal (CN) older adults at increased future risk of developing AD due to carriage of the apolipoprotein E (APOE ) ɛ 4 allele. We assessed the cross-sectional association between carbohydrate intake, cognitive performance, and cerebral amyloid-β (Aβ) load in CN older adults, genotyped for APOE ɛ 4 allele carrier status. Greater carbohydrate intake was associated with poorer performance in verbal memory in APOE ɛ 4 allele non-carriers, and poorer …performance in attention in APOE ɛ 4 allele carriers. There were no associations between carbohydrate intake and cerebral Aβ load. These results provide support to the idea that decreasing carbohydrate intake may offer neurocognitive benefits, with specific cognitive domains affected in an APOE genotype-dependent manner. These findings warrant further investigation utilizing a longitudinal study design. Show more
Keywords: Amyloid load, apolipoprotein E, attention, carbohydrates, cognition, PiB PET, verbal memory
DOI: 10.3233/JAD-161158
Citation: Journal of Alzheimer's Disease, vol. 58, no. 1, pp. 193-201, 2017
Authors: Hollands, Simone | Lim, Yen Ying | Buckley, Rachel | Pietrzak, Robert H. | Snyder, Peter J. | Ames, David | Ellis, Kathryn A. | Harrington, Karra | Lautenschlager, Nicola | Martins, Ralph N. | Masters, Colin L. | Villemagne, Victor L. | Rowe, Christopher C. | Maruff, Paul | for the AIBL Research Group
Article Type: Research Article
Abstract: Background: The detection of early Alzheimer's disease (AD) can rely on subjective and informant reports of cognitive impairment. However, relationships between subjective cognitive impairment, objectively measured cognitive function, and amyloid-β (Aβ) biomarkers remain unclear. Objective: To determine the extent to which impairment or decline in subjective and informant rated cognitive impairment was associated with memory in healthy older adults with high Aβ. Methods: Healthy older adults (n = 289) enrolled in the Australian Imaging, Biomarkers and Lifestyle (AIBL) study were studied at baseline. Pittsburgh Compound B was used to determine Aβ status at baseline. At baseline and 18 months assessments, …subjective memory impairment was assessed using the Memory Complaint Questionnaire and the Short Form of the Informant Questionnaire on Cognitive Decline in the Elderly. Cognition was measured using the Cogstate Brief Battery. Results: At baseline, there were no differences between low and high Aβ groups in subjective or informant-rated cognitive impairment, depressive and anxiety symptoms, or cognitive function. Longitudinal analyses showed moderate decline in learning and working memory over the 18 months in the high Aβ group. However there was no change over time in subjective or informant-rated cognitive impairment, depressive and anxiety symptoms, or cognition in either Aβ group. Conclusions: Although healthy older adults with high Aβ levels show decline in learning and working memory over 18 months, subjective or informant ratings of cognitive impairment do not change over the same period suggesting subjective cognitive impairment may have limited utility for the very early identification of AD. Show more
Keywords: Amyloid, cognitive, depression, subjective memory impairment
DOI: 10.3233/JAD-140678
Citation: Journal of Alzheimer's Disease, vol. 43, no. 2, pp. 677-686, 2015
Authors: Lim, Yen Ying | Ellis, Kathryn A. | Harrington, Karra | Pietrzak, Robert H. | Gale, Joanne | Ames, David | Bush, Ashley I. | Darby, David | Martins, Ralph N. | Masters, Colin L. | Rowe, Christopher C. | Savage, Greg | Szoeke, Cassandra | Villemagne, Victor L. | Maruff, Paul | For the AIBL Research Group
Article Type: Research Article
Abstract: We aimed to characterize the nature and magnitude of cognitive decline in a group of adults with amnestic mild cognitive impairment (aMCI) with high and low levels of amyloid-β (Aβ) in relation to healthy older adults with low Aβ levels. Healthy older adults and adults with aMCI enrolled in the Australian Imaging, Biomarker, and Lifestyle study, completed the CogState brief battery at baseline and 18 months, and underwent positron emission tomography neuroimaging for Aβ at baseline. In this study, we included adults with MCI who had been classified as having high and low levels of Aβ and healthy older adults …who had been classified as having low levels of Aβ. Linear model analyses adjusted for baseline cognitive function indicated that relative to healthy older adults with low Aβ, adults with aMCI and high Aβ showed greater decline in working memory and in verbal and visual episodic memory at 18 months. Adults with aMCI and low Aβ also showed greater decline in working memory; however they did not evidence any decline in episodic memory at 18 months. The results of our study suggests that relative to healthy older adults and adults with aMCI with low Aβ, adults with aMCI and high levels of Aβ showed faster rates of decline on measures of episodic memory over 18 months, and this was approximately twice that observed previously for healthy older adults with high Aβ levels. Show more
Keywords: Alzheimer's disease, amyloid-β, cognitive change, cognitive neuropsychology, mild cognitive impairment
DOI: 10.3233/JAD-121771
Citation: Journal of Alzheimer's Disease, vol. 33, no. 4, pp. 1167-1176, 2013
