Amyloid deposition and brain structure as long-term predictors of MCI, dementia, and mortality

López, Oscar L.; Becker, James T.; Chang, Yue‐Fang; Klunk, William E.; Mathis, Chester A.; Price, Julie; Aizenstein, Howard; Snitz, Beth E.; Cohen, Ann D.; DeKosky, Steven T.; Ikonomović, Miloš D.; Kamboh, M. Ilyas; Kuller, Lewis H.

doi:10.1212/wnl.0000000000005549

Cited by 39 publications

(40 citation statements)

References 33 publications

(33 reference statements)

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“…Despite the association of APOE genotype with life expectancy [22], its association with mortality in AD patients remains unclear [23]. We found no significant effect of APOE genotype on mortality, a finding that is consistent with those of several other previous studies [21, 24]. Homozygous ε4/ε4 patients tended even to have a lower risk of dying during follow-up, which may be partly explained by their younger age.…”

Section: Discussionsupporting

confidence: 88%

CSF level of β-amyloid peptide predicts mortality in Alzheimer’s disease

et al. 2019

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Objective Alzheimer’s disease (AD) is the sixth leading cause of death, with an average survival estimated between 5 and 10 years after diagnosis. Despite recent advances in diagnostic criteria of AD, few studies have used biomarker-based diagnostics to determine the prognostic factors of AD. We investigate predictors of death and institutionalization in a population of AD patients with high probability of AD physiopathology process assessed by positivity of three CSF biomarkers. Methods Three hundred twenty-one AD patients with abnormal values for CSF beta-amyloid peptide (Aβ42), tau, and phosphorylated tau levels were recruited from a memory clinic-based registry between 2008 and 2017 (Lariboisiere hospital, Paris, France) and followed during a median period of 3.9 years. We used multivariable Cox models to estimate the hazard ratio (HR) of death and institutionalization for baseline clinical data, genotype of the apolipoprotein E ( APOE ), and levels of CSF biomarkers. Results A total of 71 (22%) patients were institutionalized and 57 (18%) died during the follow-up. Greater age, male sex, lower MMSE score, and lower CSF Aβ42 level were associated with an increased risk of mortality. One standard deviation lower CSF Aβ42 (135 pg/mL) was associated with a 89% increased risk of death (95% CI = 1.25–2.86; p = 0.002). This association was not modified by age, sex, education, APOE ε4, and disease severity. There was no evidence of an association of tau CSF biomarkers with mortality. None of the CSF biomarkers were associated with institutionalization. Conclusions Lower CSF Aβ42 is a strong prognostic marker of mortality in AD patients, independently of age or severity of the disease. Whether drugs targeting beta-amyloid peptide could have an effect on mortality of AD patients should be investigated in future clinical trials.

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Section: Discussionsupporting

confidence: 88%

CSF level of β-amyloid peptide predicts mortality in Alzheimer’s disease

et al. 2019

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“…With brain atrophy on MRI a well-established risk factor for cognitive impairment, and given our current findings, we think it likely that neurodegeneration in the absence of amyloidosis is an important risk factor for MCI. Further, recent reports suggest amyloid and neurodegeneration are important complementary risk factors for dementia 18, 19 .…”

Section: Discussionmentioning

confidence: 99%

Predicting Progression to Mild Cognitive Impairment

Petersen

Lundt

Therneau

et al. 2019

Annals of Neurology

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Despite much attention to the use of biomarkers for predicting Alzheimer’s disease, little information is available at the individual level. We used the population-based Mayo Clinic Study of Aging to estimate absolute risk of cognitive impairment by biomarker group. Risk increased with age and any biomarker abnormality. For example, a 75-year-old with abnormal amyloid and cortical thinning biomarkers has ≈20% chance of cognitive impairment by age 80 whereas with normal biomarkers the chance is <10%. Persons with only one abnormal biomarker had similar intermediate risks.

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“…The first successful amyloid PET ligand was reported 15 years ago (Klunk et al , 2004), and over the past decade and a half investigators in the ageing and dementia field have thoroughly examined relationships between amyloid PET and various clinical presentations (Rabinovici et al , 2008; Nordberg et al , 2013; Villemagne et al , 2013; Ossenkoppele et al , 2015; Bilgel et al , 2018; Buckley et al , 2018; Gordon et al , 2018; Jansen et al , 2018; Lim et al , 2018; Lopez et al , 2018; Leuzy et al , 2019; Timmers et al , 2019). More recently, relationships between tau PET and various clinical presentations have also been reported (Cho et al , 2016 b ; Johnson et al , 2016; Ossenkoppele et al , 2016, 2018; Scholl et al , 2016; Chiotis et al , 2018; Maass et al , 2018; Gordon et al , 2019; Sperling et al , 2019).…”

Section: Introductionmentioning

confidence: 99%

The bivariate distribution of amyloid-β and tau: relationship with established neurocognitive clinical syndromes

Jack

Wiste

Botha

et al. 2019

Brain

144

125

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See Gordon and Tijms (doi:10.1093/brain/awz278) for a scientific commentary on this article. Jack et al. examine relationships between the bivariate distribution of β-amyloid and tau on PET and established neurocognitive clinical syndromes. Amyloidosis appears to be required for high levels of 3R/4R tau deposition. Whereas abnormal amyloid PET is compatible with normal cognition, highly abnormal tau PET is not.

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Amyloid deposition and brain structure as long-term predictors of MCI, dementia, and mortality

Cited by 39 publications

References 33 publications

CSF level of β-amyloid peptide predicts mortality in Alzheimer’s disease

CSF level of β-amyloid peptide predicts mortality in Alzheimer’s disease

Predicting Progression to Mild Cognitive Impairment

The bivariate distribution of amyloid-β and tau: relationship with established neurocognitive clinical syndromes

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