Learning deficit in cognitively normal APOE ε4 carriers with LOW β‐amyloid

ObjectiveTo evaluate the effect of midlife lipid levels on Alzheimer brain pathology 20 years later in cognitively normal elderly individuals.MethodsThis is a longitudinal cohort study of 318 cognitively normal individuals with data on fasting lipid levels at midlife (mean age 54 years). Presence of β-amyloid (Aβ) and tau pathologies 20 years later (mean age 73 years) were detected by quantifying Alzheimer disease (AD) biomarkers in CSF. In a subset (n = 134), Aβ (18F-flutemetamol) PET was also performed.ResultsCSF Aβ42 and Aβ PET revealed Aβ pathology in approximately 20% of the cognitively healthy population and CSF Aβ42/phosphorylated tau (p-tau) ratio indicated both Aβ and tau pathology in 16%. Higher levels of triglycerides in midlife were independently associated with abnormal CSF Aβ42 (odds ratio [OR] 1.34, 95% confidence interval [CI] 1.03–1.75, p = 0.029) and abnormal Aβ42/p-tau ratio (OR 1.46, 95% CI 1.10–1.93; p = 0.009) adjusting for age, sex, APOE ε4, education, and multiple vascular risk factors. Triglycerides were also associated with abnormal Aβ PET in multivariable regression models, but the association was attenuated in the fully adjusted model. Increased levels of medium and large low-density lipoprotein subfractions were significantly associated with abnormal Aβ PET and large high-density lipoprotein particles were associated with decreased risk of abnormal Aβ PET.ConclusionsIncreased levels of triglycerides at midlife predict brain Aβ and tau pathology 20 years later in cognitively healthy individuals. Certain lipoprotein subfractions may also be risk factors for Aβ pathology. These findings further support an involvement of lipids in the very early stages of AD development.

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O3-10-01: DIFFERENT EFFECTS OF APOE ε4 ALLELE ON THE RELATIONSHIP BETWEEN TAU AND β-AMYLOID IN EARLY-ONSET AND LATE-ONSET ALZHEIMER DISEASE

Alzheimer s & Dementia ◽

10.1016/j.jalz.2018.06.2825 ◽

2006 ◽

Vol 14 (7S_Part_19) ◽

pp. P1039-P1040

Author(s):

Young Noh ◽

Tae Sung Lim ◽

Sang-Yoon Lee ◽

Kee Hyung Park ◽

Dong Jin Shin ◽

...

Keyword(s):

Alzheimer Disease ◽

Early Onset ◽

Late Onset ◽

Apoe Ε4 ◽

Ε4 Allele ◽

Β Amyloid ◽

The Relationship

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β-Amyloid, APOE and BDNF Genotype, and Depressive and Anxiety Symptoms in Cognitively Normal Older Women and Men

American Journal of Geriatric Psychiatry ◽

10.1016/j.jagp.2016.08.007 ◽

2016 ◽

Vol 24 (12) ◽

pp. 1191-1195 ◽

Cited By ~ 10

Author(s):

Sophie E. Holmes ◽

Irina Esterlis ◽

Carolyn M. Mazure ◽

Yen Ying Lim ◽

David Ames ◽

...

Keyword(s):

Older Women ◽

Anxiety Symptoms ◽

Cognitively Normal ◽

Β Amyloid

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Interactive effect of age and APOE-ε4 allele load on white matter myelin content in cognitively normal middle-aged subjects

NeuroImage Clinical ◽

10.1016/j.nicl.2019.101983 ◽

2019 ◽

Vol 24 ◽

pp. 101983 ◽

Cited By ~ 3

Author(s):

Grégory Operto ◽

José Luis Molinuevo ◽

Raffaele Cacciaglia ◽

Carles Falcon ◽

Anna Brugulat-Serrat ◽

...

Keyword(s):

White Matter ◽

Interactive Effect ◽

Middle Aged ◽

Cognitively Normal ◽

Apoe Ε4 ◽

Ε4 Allele ◽

Aged Subjects ◽

Effect Of Age

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P3-367: WHITE MATTER HYPERINTENSITY AND β-AMYLOID BURDEN IN A PRECLINICAL COGNITIVELY NORMAL COHORT

Alzheimer s & Dementia ◽

10.1016/j.jalz.2019.06.3400 ◽

2019 ◽

Vol 15 ◽

pp. P1087-P1087

Author(s):

Kaikai Shen ◽

Pratishtha Chatterjee ◽

Ying Xia ◽

Kathryn Goozee ◽

Jurgen Fripp ◽

...

Keyword(s):

White Matter ◽

White Matter Hyperintensity ◽

Amyloid Burden ◽

Cognitively Normal ◽

Β Amyloid

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FINANCIAL MANAGEMENT SKILLS IN AGING, MCI AND DEMENTIA: CROSS SECTIONAL RELATIONSHIP TO 18F-FLORBETAPIR PET CORTICAL Β-AMYLOID DEPOSITION

Journal of Prevention of Alzheimer's Disease ◽

10.14283/jpad.2019.26 ◽

2019 ◽

pp. 1-9

Author(s):

S. Tolbert ◽

Y. Liu ◽

C. Hellegers ◽

J.R. Petrella ◽

M.W. Weiner ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

At Risk ◽

Amyloid Deposition ◽

Cross Sectional ◽

Cognitively Normal ◽

Financial Capacity ◽

Cohen’S D ◽

Β Amyloid ◽

Cohen's D

Background: There is a need to more fully characterize financial capacity losses in the preclinical and prodromal stages of Alzheimer’s disease (AD) and their pathological substrates. Objectives: To test the association between financial skills and cortical β-amyloid deposition in aging and subjects at risk for AD. Design: Cross-sectional analyses of data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI-3) study conducted across 50 plus sites in the US and Canada. Setting: Multicenter biomarker study. Participants: 243 subjects (144 cognitively normal, 79 mild cognitive impairment [MCI], 20 mild AD). Measurements: 18F-Florbetapir brain PET scans to measure global cortical β-amyloid deposition (SUVr) and the Financial Capacity Instrument Short Form (FCI-SF) to evaluate an individual’s financial skills in monetary calculation, financial concepts, checkbook/register usage, and bank statement usage. There are five sub scores and a total score (range of 0–74) with higher scores indicating better financial skill. Results: FCI-SF total score was significantly worse in MCI [Cohen’s d= 0.9 (95%CI: 0.6-1.2)] and AD subjects [Cohen’s d=3.1(CI: 2.5-3.7)] compared to normals. Domain scores and completion times also showed significant difference. Across all subjects, higher cortical β-amyloid SUVr was significantly associated with worse FCI-SF total score after co-varying for age, education, and cognitive score [Cohen’s f2=0.751(CI: 0.5-1.1)]. In cognitively normal subjects, after covarying for age, gender, and education, higher β -amyloid PET SUVr was associated with longer task completion time [Cohen’s f2=0.198(CI: 0.06-0.37)]. Conclusion: Using a multicenter study sample, we document that financial capacity is impaired in the prodromal and mild stages of AD and that such impairments are, in part, associated with the extent of cortical β-amyloid deposition. In normal aging, β-amyloid deposition is associated with slowing of financial tasks. These data confirm and extend prior research highlighting the utility of financial capacity assessments in at risk samples.

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Association of amyloid-β CSF/PET discordance and tau load 5 years later

Neurology ◽

10.1212/wnl.0000000000010739 ◽

2020 ◽

Vol 95 (19) ◽

pp. e2648-e2657 ◽

Cited By ~ 1

Author(s):

Juhan Reimand ◽

Lyduine Collij ◽

Philip Scheltens ◽

Femke Bouwman ◽

Rik Ossenkoppele ◽

...

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Amyloid Β ◽

Csf Biomarkers ◽

Tau Pathology ◽

Cognitively Normal ◽

Amyloid Aβ ◽

Β Amyloid ◽

Tau Pet

ObjectiveTo investigate the association between discordant β-amyloid (Aβ) PET and CSF biomarkers at baseline and the emergence of tau pathology 5 years later.MethodsWe included 730 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants without dementia (282 cognitively normal, 448 mild cognitive impairment) with baseline [18F]florbetapir PET and CSF Aβ42 available. Aβ CSF/PET status was determined at baseline using established cutoffs. Longitudinal data were available for [18F]florbetapir (Aβ) PET (baseline to 4.3 ± 1.9 years), CSF (p)tau (baseline to 2.0 ± 0.1 years), cognition (baseline to 4.3 ± 2.0 years), and [18F]flortaucipir (tau) PET (measured 5.2 ± 1.2 years after baseline to 1.6 ± 0.7 years later). We used linear mixed modeling to study the association between Aβ CSF/PET status and tau pathology measured in CSF or using PET. We calculated the proportion of CSF+/PET− participants who during follow-up (1) progressed to Aβ CSF+/PET+ or (2) became tau-positive based on [18F]flortaucipir PET.ResultsAβ CSF+/PET+ (n = 318) participants had elevated CSF (p)tau levels and worse cognitive performance at baseline, while CSF+/PET− (n = 80) participants were overall similar to the CSF−/PET− (N = 306) group. Five years after baseline, [18F]flortaucipir PET uptake in the CSF+/PET− group (1.20 ± 0.13) did not differ from CSF−/PET− (1.18 ± 0.08, p = 0.69), but was substantially lower than CSF+/PET+ (1.48 ± 0.44, p < 0.001). Of the CSF+/PET− participants, 21/64 (33%) progressed to Aβ CSF+/PET+, whereas only one (3%, difference p < 0.05) became tau-positive based on [18F]flortaucipir PET.ConclusionsAβ load detectable by both CSF and PET seems to precede substantial tau deposition. Compared to participants with abnormal Aβ levels on both PET and CSF, the CSF+/PET− group has a distinctly better prognosis.

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