%0 Journal Article %J J Alzheimers Dis %D 2024 %T Interaction Between Arteriosclerosis and Amyloid-β on Cognitive Function. %A Frentz, Ingeborg %A van Arendonk, Joyce %A Leeuwis, Anna E %A Vernooij, Meike W %A van der Flier, Wiesje M %A Bos, Daniel %A De Deyn, Peter Paul %A Wolters, Frank J %A Ikram, M Arfan %K Aged %K Alzheimer Disease %K Amyloid beta-Peptides %K Arteriosclerosis %K Biomarkers %K Cognition %K Cognitive Dysfunction %K Female %K Humans %K Male %K tau Proteins %X

BACKGROUND: Dementia is a multifactorial disease, with Alzheimer's disease (AD) and vascular pathology often co-occurring in many individuals with dementia. Yet, the interplay between AD and vascular pathology in cognitive decline is largely undetermined.

OBJECTIVE: The aim of the present study was to examine the joint effect of arteriosclerosis and AD pathology on cognition in the general population without dementia.

METHODS: We determined the interaction between blood-based AD biomarkers and CT-defined arteriosclerosis on cognition in 2,229 dementia-free participants of the population-based Rotterdam Study (mean age: 68.9 years, 52% women) cross-sectionally.

RESULTS: Amyloid-β (Aβ)42 and arterial calcification were associated with cognitive performance. After further adjustment for confounders in a model that combined all biomarkers, only arterial calcification remained independently associated with cognition. There was a significant interaction between arterial calcification and Aβ42 and between arterial calcification and the ratio of Aβ42/40. Yet, estimates attenuated, and interactions were no longer statistically significant after adjustment for cardio metabolic risk factors.

CONCLUSIONS: Arteriosclerosis and AD display additive interaction-effects on cognition in the general population, that are due in part to cardio metabolic risk factors. These findings suggest that joint assessment of arteriosclerosis and AD pathology is important for understanding of disease etiology in individuals with cognitive impairment.

%B J Alzheimers Dis %V 97 %P 953-961 %8 2024 %G eng %N 2 %1 https://www.ncbi.nlm.nih.gov/pubmed/38217596?dopt=Abstract %R 10.3233/JAD-230604 %0 Journal Article %J J Alzheimers Dis %D 2018 %T Association of Cerebrospinal Fluid (CSF) Insulin with Cognitive Performance and CSF Biomarkers of Alzheimer's Disease. %A Geijselaers, Stefan L C %A Aalten, Pauline %A Ramakers, Inez H G B %A De Deyn, Peter Paul %A Heijboer, Annemieke C %A Koek, Huiberdina L %A OldeRikkert, Marcel G M %A Papma, Janne M %A Reesink, Fransje E %A Smits, Lieke L %A Stehouwer, Coen D A %A Teunissen, Charlotte E %A Verhey, Frans R J %A van der Flier, Wiesje M %A Biessels, Geert Jan %K Aged %K Alzheimer Disease %K Amyloid beta-Peptides %K Apolipoprotein E4 %K Brain %K Cognition Disorders %K Female %K Humans %K Insulin %K Male %K Mental Status Schedule %K Middle Aged %K Neuropsychological Tests %K Peptide Fragments %K Signal Transduction %K tau Proteins %X

BACKGROUND: Abnormal insulin signaling in the brain has been linked to Alzheimer's disease (AD).

OBJECTIVE: To evaluate whether cerebrospinal fluid (CSF) insulin levels are associated with cognitive performance and CSF amyloid-β and Tau. Additionally, we explore whether any such association differs by sex or APOE ɛ4 genotype.

METHODS: From 258 individuals participating in the Parelsnoer Institute Neurodegenerative Diseases, a nationwide multicenter memory clinic population, we selected 138 individuals (mean age 66±9 years, 65.2% male) diagnosed with subjective cognitive impairment (n = 45), amnestic mild cognitive impairment (n = 44), or AD (n = 49), who completed a neuropsychological assessment, including tests of global cognition and memory performance, and who underwent lumbar puncture. We measured CSF levels of insulin, amyloid-β1-42, total (t-)Tau, and phosphorylated (p-)Tau.

RESULTS: CSF insulin levels did not differ between the diagnostic groups (p = 0.136). Across the whole study population, CSF insulin was unrelated to cognitive performance and CSF biomarkers of AD, after adjustment for age, sex, body mass index, diabetes status, and clinic site (all p≥0.131). Importantly, however, we observed effect modification by sex and APOE ɛ4 genotype. Specifically, among women, higher insulin levels in the CSF were associated with worse global cognition (standardized regression coefficient -0.483; p = 0.008) and higher p-Tau levels (0.353; p = 0.040). Among non-carriers of the APOE ɛ4 allele, higher CSF insulin was associated with higher t-Tau (0.287; p = 0.008) and p-Tau (0.246; p = 0.029).

CONCLUSION: Our findings provide further evidence for a relationship between brain insulin signaling and AD pathology. It also highlights the need to consider sex and APOE ɛ4 genotype when assessing the role of insulin.

%B J Alzheimers Dis %V 61 %P 309-320 %8 2018 %G eng %N 1 %1 http://www.ncbi.nlm.nih.gov/pubmed/29154275?dopt=Abstract %R 10.3233/JAD-170522 %0 Journal Article %J J Alzheimers Dis %D 2016 %T Diagnostic Impact of Cerebrospinal Fluid Biomarker (Pre-)Analytical Variability in Alzheimer's Disease. %A Niemantsverdriet, Ellis %A Goossens, Joery %A Struyfs, Hanne %A Martin, Jean-Jacques %A Goeman, Johan %A De Deyn, Peter Paul %A Vanderstichele, Hugo %A Engelborghs, Sebastiaan %K Aged %K Aged, 80 and over %K Alzheimer Disease %K Amyloid beta-Peptides %K Autopsy %K Cognitive Dysfunction %K Enzyme-Linked Immunosorbent Assay %K Exercise %K Female %K Follow-Up Studies %K Humans %K Male %K Middle Aged %K Peptide Fragments %K Psychiatric Status Rating Scales %K Retrospective Studies %K Statistics, Nonparametric %K tau Proteins %X

Intra- and inter-laboratory variability of cerebrospinal fluid (CSF) biomarker analyses remains an important issue. We investigated the clinical-diagnostic impact of CSF biomarker concentration shifts in mild cognitive impairment (MCI) and autopsy-confirmed Alzheimer's disease (AD) dementia patients. MCI patients (n = 85), autopsy-confirmed AD dementia patients (n = 72), and cognitively healthy controls (n = 100) were included in this prospective, longitudinal study. AD dementia patients were followed up until death, and controls were included from 1992 until 2003. In-house validated cutoff values of biomarkers were applied: Aβ1-42 <638.5 pg/mL, T-tau>296.5 pg/mL, P-tau(181P) >56.5 pg/mL. Both increments and decrements (from ± 5% to ± 40% ) were added to the true (=observed) CSF biomarker values, imitating the anticipated differences in biomarker concentrations. Within certain limits, the clinical diagnostic performance of AD CSF biomarkers remains largely unchanged and clinical diagnostic accuracy deviated less than 8.2% from the reference when concentration shifts ranging between -20% and +20% were added to one of the three CSF biomarkers in MCI and autopsy-confirmed AD patients. Notwithstanding the fact that (pre- and post-)analytical parameters can affect the clinical classification, the present exploratory study provides evidence that for a specific context of use, the impact on clinical accuracy of biomarker concentration shifts might be lower than originally expected. In conclusion, induced shifts of ±20% in only one of the three biomarkers has limited impact on the clinical accuracy of AD CSF biomarkers in MCI and autopsy-confirmed AD patients when using the IWG-2 criteria.

%B J Alzheimers Dis %V 51 %P 97-106 %8 2016 %G eng %N 1 %1 http://www.ncbi.nlm.nih.gov/pubmed/26836187?dopt=Abstract %R 10.3233/JAD-150953