Cystatin C, cognition, and brain MRI findings in 90+-year-olds

Lau, Wei Ling; Fisher, Mark; Greenia, Dana; Floriolli, David; Fletcher, Evan; Singh, Baljeet; Corrada, María M.; Whittle, Christina; Kawas, Claudia H.; Paganini‐Hill, Annlia

doi:10.1016/j.neurobiolaging.2020.04.022

Cited by 22 publications

(35 citation statements)

References 45 publications

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“…The current study demonstrates a significant association between brain amyloid-β burden (measured on PET scan) and cognitive impairment in an oldest-old cohort from The 90+ Study, but no association between cystatin C eGFR or CKD stage and brain amyloid-β burden. We have previously reported significant association between CKD, indices of cerebral microvascular disease, and cognitive decline in the same cohort ( 4 ). Collectively, our work suggests that decreased kidney function and brain amyloid-β burden impact cognition via different pathophysiologic pathways.…”

Section: Discussion/conclusionmentioning

confidence: 68%

“…CKD-associated cerebral small vessel disease includes microbleeds, microinfarcts, lacunes, white matter or global atrophy, and arteriolosclerosis ( 5 ). In a prior analysis of The 90+ Study cohort, lower kidney function correlated with impaired global cognition, executive function, and visual-spatial ability; infratentorial microbleeds; and lower gray matter volume ( 4 ). Risk of incident dementia in the highest cystatin C tertile was 3.81 (adjusted for age, sex, education, and comorbid conditions) and was attenuated when microbleeds were included in the risk model, suggesting that the impact of CKD on cognitive dysfunction is partly mediated by microbleeds ( 4 ).…”

Section: Discussion/conclusionmentioning

confidence: 99%

“…We report results from a subset of participants of The 90+ Study, an ongoing longitudinal study of aging and dementia in people aged 90 or older ( 4 , 20 , 21 ). Participants of The 90+ Study were recruited from two groups: (1) survivors of the Leisure World Cohort Study ( 20 ), an epidemiological health study established in the 1980s of the residents of Leisure World, a retirement community in Orange County, California, who were aged 90 or older on or after January 1, 2003, when enrollment into The 90+ Study commenced, and (2) 90+ year-old residents of Orange County, California, who lived within a 2-h drive of the study location, and joined the study through open recruitment ( 21 ).…”

Section: Methodsmentioning

confidence: 99%

“…Participants were seen every 6 months and given a standard battery of 10 neuropsychological tests indexing multiple cognitive domains and including the Modified Mini-Mental State Examination (3MS), by trained and certified psychometrists. Participants also underwent a neurological exam by neurological examiners (trained physicians or nurse practitioners) to determine cognitive status (normal, cognitive impairment no dementia [CIND], or dementia) ( 4 , 23 ). During this visit, medical history was also updated.…”

Section: Methodsmentioning

confidence: 99%

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Kidney Function Is Not Related to Brain Amyloid Burden on PET Imaging in The 90+ Study Cohort

et al. 2021

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Cognitive decline is common in chronic kidney disease (CKD). While the evidence of vascular cognitive impairment in this population is robust, the role of Alzheimer's pathology is unknown. We evaluated serum cystatin C-estimated glomerular filtration rate (eGFR), brain amyloid-β positron emission tomography (PET) imaging, and cognitive function in 166 participants from The 90+ Study. Mean age was 93 years (range 90-107) and 101 (61%) were women; 107 participants had normal cognitive status while 59 participants had cognitive impairment no dementia (CIND) or dementia. Mean ± standard deviation cystatin C was 1.59 ± 0.54 mg/L with eGFR 40.7 ± 18.7 ml/min/1.73m2. Higher amyloid-β burden was associated with dementia, but not with age, diabetes, hypertension, or cardiovascular disease. We found no association between brain amyloid-β burden and cystatin C eGFR. We previously reported that kidney function was associated with cognition and cerebral microbleeds in the same cohort of oldest-old adults (90+ years old). Collectively, these findings suggest that microvascular rather than Alzheimer's pathology drives CKD-associated cognitive dysfunction in this population.

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Section: Discussion/conclusionmentioning

confidence: 68%

Section: Discussion/conclusionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Kidney Function Is Not Related to Brain Amyloid Burden on PET Imaging in The 90+ Study Cohort

et al. 2021

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“…Although the importance of some risk factors for dementia appears to decline with increasing age, other risk factors have drawn attention in the oldest-old. Lower physical strength and performance, less participation in cognitive stimulating activities, and lower kidney function have been associated with cognitive impairment in the oldest-old [ 17 ▪ , 18 ▪ , 19 ]. Although it is difficult to disentangle cause and effect in these relationships, preserving physical health seems to be of utmost importance to preserve cognitive health in the oldest-old [ 20 ].…”

Section: Text Of Reviewmentioning

confidence: 99%

What have we learned from cognition in the oldest-old

Kawas

Legdeur

Corrada

2021

Current Opinion in Neurology

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Purpose of review People over 90 are the fastest growing segment of the population with the highest rates of dementia. This review highlights recent findings that provide insight to our understanding of dementia and cognition at all ages. Recent findings Risk factors for Alzheimer's disease (AD) and dementia differ by age, with some factors, like the development of hypertension, actually becoming protective in the oldest-old. At least half of all dementia in this age group is due to non AD pathologies, including microinfarcts, hippocampal sclerosis and TDP-43. The number of pathologic changes found in the brain is related to both risk and severity of dementia, but many people in this age group appear to be ‘resilient’ to these pathologies. Resilience to Alzheimer pathology, in part, may be related to absence of other pathologies, and imaging and spinal fluid biomarkers for AD have limited utility in this age group. Summary Studies of dementia in the oldest-old are important for our understanding and eventual treatment or prevention of dementia at all ages.

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Association of impaired kidney function with dementia and brain pathologies: A community‐based cohort study

Wang

Dove

et al. 2022

Alzheimer's & Dementia

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Introduction The relationship between impaired kidney function (KF), dementia, and brain pathologies remains unclear. Methods A total of 1354 dementia‐ and kidney disease‐free participants including 895 with normal and 459 with impaired KF were followed from 2002 until 2020 (median [interquartile range]: 5 [2–9]) to detect incident dementia. KF was assessed at baseline and categorized as normal or impaired. Over the follow‐up, 453 participants died and underwent autopsies for neuropathological assessment. Results Compared to those with normal KF, the hazard ratios (95% confidence intervals [CIs]) of those with impaired KF was 1.48 (1.15, 1.90)/1.44 (1.10, 1.88) for dementia/Alzheimer's dementia. Furthermore, impaired KF was related to a significantly higher burden of cerebral amyloid angiopathy (CAA; odds ratio = 1.96, 95% CI: 1.17, 3.30), but not to other brain pathologies. Discussion Impaired KF is associated with an increased risk of dementia and Alzheimer's dementia. CAA may underlie, in part, this association. Highlights Impaired kidney function (KF) was associated with higher dementia and Alzheimer's dementia risk. Impaired KF anticipated dementia and Alzheimer's dementia onset by more than 1.5 years. Impaired KF was significantly related to a higher burden of cerebral amyloid angiopathy (CAA) but not to other brain pathologies.

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Cystatin C, cognition, and brain MRI findings in 90+-year-olds

Cited by 22 publications

References 45 publications

Kidney Function Is Not Related to Brain Amyloid Burden on PET Imaging in The 90+ Study Cohort

Kidney Function Is Not Related to Brain Amyloid Burden on PET Imaging in The 90+ Study Cohort

What have we learned from cognition in the oldest-old

Association of impaired kidney function with dementia and brain pathologies: A community‐based cohort study

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