Osset-Malla Mariona, Martínez-Velasco Aitana, Sánchez-Benavides Gonzalo, Buongiorno Mariateresa, de la Sierra Alejandro, Shekari Mahnaz, Minguillon Carolina, Kollmorgen Gwendlyn, Quijano-Rubio Clara, Zetterberg Henrik, Blennow Kaj, García David Vállez, Suárez-Calvet Marc, Gispert Juan Domingo, Grau-Rivera Oriol
Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain.
Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain; Hospital del Mar Research Institute, Barcelona, Spain; Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, Madrid, Spain.
J Prev Alzheimers Dis. 2025 Aug 11:100304. doi: 10.1016/j.tjpad.2025.100304.
Hypertension is a modifiable risk factor for dementia, potentially influencing Alzheimer's disease (AD) pathology. Understanding this relationship is essential for developing interventions to reduce dementia risk.
We investigated cross-sectional and longitudinal associations between blood pressure and AD biomarkers in cerebrospinal fluid (CSF) and amyloid (Aβ) positron emission tomography (PET) in cognitively unimpaired adults.
Prospective observational study.
We analyzed data from cognitively unimpaired participants from three observational prospective European studies: ALFA+ (NCT02485730), EPAD-LCS (NCT02804789), and AMYPAD PNHS (EudraCT: 2018-002,277-22).
ALFA+ participants had either CSF biomarkers (CSF Aβ42, Aβ40, p-tau181, t-tau) and/or Aβ PET data. EPAD participants had CSF biomarkers (CSF Aβ42, p-tau181, t-tau), and AMYPAD participants had Aβ PET data. All participants had available data about diabetes, use of hypertensive medication, and waist-to-hip ratio. Multivariable linear regression models were used to analyze cross-sectional associations between systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP) with CSF biomarkers or Aβ PET (Centiloid units, CL); longitudinal associations were tested by means of delta CL scores between baseline and follow-up to assess Aβ PET changes over time.
We included 405 participants from ALFA+ (mean age 61.1 years; 60 % female), 1104 from EPAD (mean age 64.8 years; 59.1 % female), and 340 from AMYPAD (mean age 71.8 years; 60 % female). In ALFA+, DBP was negatively associated with CSF Aβ40 (p = 0.016) and p-tau181 (p = 0.050), while there was a non-significant trend towards a positive association between SBP and CL over time (p = 0.058). In EPAD, DBP was negatively associated with CSF Aβ42 (p < 0.001) and p-tau181 (p = 0.014), while PP was positively associated with CSF Aβ42 (p = 0.024). In AMYPAD, SBP (p = 0.002) and PP (p = 0.003) were positively associated with CL at baseline, with a similar non-significant trend being found for DBP (p = 0.089). Higher DBP (p = 0.042) was significantly associated to increased CL over time, with a similar non-significant trend being found for SBP (p = 0.072). We did not find significant associations between blood pressure and longitudinal changes in CSF biomarkers.
Elevated blood pressure was associated with increased Aβ PET accumulation in cognitively unimpaired individuals. Further research is warranted to elucidate potential mechanisms underlying the negative associations between DBP and CSF biomarkers, which do not reflect the typical AD molecular signature. These findings highlight the relevance of high blood pressure as a potential risk factor for cognitive decline.
高血压是痴呆的一个可改变的风险因素，可能影响阿尔茨海默病（AD）的病理过程。了解这种关系对于开发降低痴呆风险的干预措施至关重要。
我们调查了认知功能未受损的成年人中血压与脑脊液（CSF）生物标志物以及淀粉样蛋白（Aβ）正电子发射断层扫描（PET）之间的横断面和纵向关联。
前瞻性观察性研究。
我们分析了来自三项欧洲前瞻性观察性研究中认知功能未受损参与者的数据：ALFA+（NCT02485730）、EPAD-LCS（NCT02804789）和AMYPAD PNHS（欧盟临床试验注册号：2018-002,277-22）。
ALFA+参与者有脑脊液生物标志物（脑脊液Aβ42、Aβ40、p-tau181、t-tau）和/或Aβ PET数据。EPAD参与者有脑脊液生物标志物（脑脊液Aβ42、p-tau181、t-tau），AMYPAD参与者有Aβ PET数据。所有参与者都有关于糖尿病、高血压药物使用和腰臀比的可用数据。多变量线性回归模型用于分析收缩压（SBP）、舒张压（DBP）和脉压（PP）与脑脊液生物标志物或Aβ PET（百分单位，CL）之间的横断面关联；纵向关联通过基线和随访之间的CL分数变化来测试，以评估Aβ PET随时间的变化。
我们纳入了405名来自ALFA+的参与者（平均年龄61.1岁；60%为女性）、1104名来自EPAD的参与者（平均年龄64.8岁；59.1%为女性）和340名来自AMYPAD的参与者（平均年龄71.8岁；60%为女性）。在ALFA+中，DBP与脑脊液Aβ40（p = 0.016）和p-tau181（p = 0.050）呈负相关，而SBP与CL随时间呈正相关的趋势不显著（p = 0.058）。在EPAD中，DBP与脑脊液Aβ42（p < 0.001）和p-tau181（p = 0.014）呈负相关，而PP与脑脊液Aβ42呈正相关（p = 0.024）。在AMYPAD中，SBP（p = 0.002）和PP（p = 0.003）在基线时与CL呈正相关，DBP也有类似的不显著趋势（p = 0.089）。较高的DBP（p = 0.042）与随时间CL增加显著相关，SBP也有类似的不显著趋势（p = 0.072）。我们未发现血压与脑脊液生物标志物的纵向变化之间存在显著关联。
血压升高与认知功能未受损个体中Aβ PET积累增加有关。有必要进一步研究以阐明DBP与脑脊液生物标志物之间负相关的潜在机制，这些负相关并不反映典型的AD分子特征。这些发现突出了高血压作为认知衰退潜在风险因素的相关性。
