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J Alzheimers Dis ; 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32039855


BACKGROUND: High visit-to-visit blood pressure variability (BPV) has been associated with cognitive decline and cerebral small vessel disease (cSVD), in particular cerebrovascular lesions. Whether day-to-day BPV also relates to cSVD has not been investigated. OBJECTIVE: To investigate the cross-sectional association between day-to-day BPV and total cSVD MRI burden in older memory clinic patients. METHODS: We included outpatients referred to our memory clinic, who underwent cerebral MRI as part of their diagnostic assessment. We determined the validated total cSVD score (ranging from 0-4) by combining four markers of cSVD that were visually rated. Home blood pressure (BP) measurements were performed for one week, twice a day, according to international guidelines. BPV was defined as the within-subject coefficient of variation (CV; standard deviation/mean BP*100). We used multivariable ordinal logistic regression analyses adjusted for age, sex, smoking, diabetes, antihypertensive medication, history of cardiovascular disease, and mean BP. RESULTS: For 82 patients (aged 71.2±7.9 years), mean home BP was 140/79±15/9 mmHg. Dementia and mild cognitive impairment were diagnosed in 46% and 34%, respectively. 78% had one or more markers of cSVD. Systolic CV was associated with cSVD burden (adjusted odds ratio per point increase in CV = 1.29, 95% confidence interval = 1.04-1.60, p = 0.022). There were no differences in diastolic CV and mean BP between the cSVD groups. When we differentiated between morning and evening BP, only evening BPV remained significantly associated with total cSVD burden. CONCLUSION: Day-to-day systolic BPV is associated with cSVD burden in memory clinic patients. Future research should indicate whether lowering BPV should be included in BP management in older people with memory complaints.

Hypertension ; 74(5): 1172-1180, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31542965


Blood pressure variability (BPV) has been shown to have predictive value over blood pressure (BP) levels alone in stroke patients. We assessed whether BPV predicts cognitive and functional decline in Alzheimer disease, using data from a randomized trial (NILVAD [A European Multicentre Double-blind Placebo-controlled Phase III Trial of Nilvadipine in Mild to Moderate Alzheimer's Disease]). Patients with mild-to-moderate Alzheimer disease were included if they had ≥3 office BP measurements available to determine visit-to-visit BPV. Day-to-day BPV was assessed using home BP measurements in a subsample. The variation independent of mean was used to calculate BPV. Outcomes were change in Alzheimer's Disease Assessment Scale-cognitive subscale-12 and Disability Assessment for Dementia after 1 and 1.5 years. A total of 460 patients aged 72.1 (SD=8.1) years, with mean BP of 134.0/75.1 (10.9/6.3) mm Hg were included. After 1 year, patients in the highest quartile of BPV had deteriorated more on Alzheimer's Disease Assessment Scale-cognitive subscale compared with patients in the lowest quartile (systolic: ß, 2.24 [95% CI, 0.11-4.38], P=0.040; diastolic: ß, 2.54 [95% CI, 0.33-4.75] P=0.024). This association was still present after 1.5 years (systolic: ß, 2.86 [95% CI, 0.35-5.36], P=0.026; diastolic: ß, 3.30 [95% CI, 0.67-5.93], P=0.014). There was no effect of visit-to-visit BPV on Disability Assessment for Dementia. Day-to-day BPV was available for 46 patients. Significant associations were observed between day-to-day BPV and deterioration on Alzheimer's Disease Assessment Scale-cognitive subscale (systolic: P=0.036) and Disability Assessment for Dementia (systolic: P=0.020; diastolic: P=0.007) after 1 year, but not after 1.5 years. All associations were adjusted for potential confounders, including intervention group. In conclusion, this post hoc analysis indicates that higher visit-to-visit and day-to-day BPV might be associated with progression of Alzheimer disease. Targeting BPV may be a future target to slow decline in patients with Alzheimer disease. Clinical Trial Registration URL: Unique identifier: NCT02017340.

Doença de Alzheimer/fisiopatologia , Anti-Hipertensivos/uso terapêutico , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Nifedipino/análogos & derivados , Idoso , Doença de Alzheimer/epidemiologia , Determinação da Pressão Arterial/métodos , Transtornos Cognitivos/epidemiologia , Transtornos Cognitivos/fisiopatologia , Intervalos de Confiança , Progressão da Doença , Método Duplo-Cego , Feminino , Humanos , Hipertensão/epidemiologia , Modelos Lineares , Masculino , Testes de Estado Mental e Demência , Pessoa de Meia-Idade , Análise Multivariada , Nifedipino/uso terapêutico , Prognóstico , Medição de Risco , Índice de Gravidade de Doença
Hypertension ; 74(2): 413-420, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31203725


Cerebrovascular changes, including reduced cerebral blood flow (CBF), occur early in the development of Alzheimer disease and may accelerate disease progression. This randomized, double-blind, placebo-controlled study investigated how 6 months of treatment with the calcium antagonist nilvadipine would affect CBF in patients with mild-to-moderate Alzheimer disease. CBF was measured with magnetic resonance arterial spin labeling in whole-brain gray matter and in a priori defined regions of interest including the hippocampus. Fifty-eight patients were randomly assigned (29 in each group), of whom 22 in both groups had no magnetic resonance exclusion criteria and were medication compliant over 6 months. Mean age was 72.8±6.2 years, mean mini-mental state examination was 20.4±3.4. Nilvadipine treatment lowered systolic blood pressure (Δ=-11.5 [95% CI, -19.7 to -3.2] mm Hg; P<0.01), while whole-brain gray-matter CBF remained stable (Δ=5.4 [95% CI, -6.4 to 17.2] mL/100 g per minute; P=0.36). CBF in the hippocampus increased (left: Δ=24.4 [95% CI, 4.3-44.5] mL/100 g per minute; P=0.02; right: Δ=20.1 [95% CI, -0.6 to 40.8] mL/100 g per minute; P=0.06). There was no significant change in CBF in the posterior cingulate cortex (Δ=5.2 [95% CI, -16.5 to 27.0] mL/100 g per minute; P=0.63) or other regions of interest. In conclusion, nilvadipine reduced blood pressure and increased CBF in the hippocampus, whereas other regions showed stable or small nonsignificant increases in CBF. These findings not only indicate preserved cerebral autoregulation in Alzheimer disease but also point toward beneficial cerebrovascular effects of antihypertensive treatment. Clinical Trial Registration- URL: . Unique identifier: NCT02017340.

Doença de Alzheimer/diagnóstico , Doença de Alzheimer/tratamento farmacológico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Circulação Cerebrovascular/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Nifedipino/análogos & derivados , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/epidemiologia , Método Duplo-Cego , Feminino , Humanos , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Países Baixos , Nifedipino/uso terapêutico , Prognóstico , Valores de Referência , Medição de Risco , Índice de Gravidade de Doença , Resultado do Tratamento , Ultrassonografia Doppler/métodos
J Am Heart Assoc ; 8(10): e011938, 2019 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-31088188


Background Hypertension is common among patients with Alzheimer disease. Because this group has been excluded from hypertension trials, evidence regarding safety of treatment is lacking. This secondary analysis of a randomized controlled trial assessed whether antihypertensive treatment increases the prevalence of orthostatic hypotension (OH) in patients with Alzheimer disease. Methods and Results Four hundred seventy-seven patients with mild-to-moderate Alzheimer disease were randomized to the calcium-channel blocker nilvadipine 8 mg/day or placebo for 78 weeks. Presence of OH (blood pressure drop ≥20/≥10 mm Hg after 1 minute of standing) and OH-related adverse events (dizziness, syncope, falls, and fractures) was determined at 7 follow-up visits. Mean age of the study population was 72.2±8.2 years and mean Mini-Mental State Examination score was 20.4±3.8. Baseline blood pressure was 137.8±14.0/77.0±8.6 mm Hg. Grade I hypertension was present in 53.4% (n=255). After 13 weeks, blood pressure had fallen by -7.8/-3.9 mm Hg for nilvadipine and by -0.4/-0.8 mm Hg for placebo ( P<0.001). Across the 78-week intervention period, there was no difference between groups in the proportion of patients with OH at a study visit (odds ratio [95% CI]=1.1 [0.8-1.5], P=0.62), nor in the proportion of visits where a patient met criteria for OH, corrected for number of visits (7.7±13.8% versus 7.3±11.6%). OH-related adverse events were not more often reported in the intervention group compared with placebo. Results were similar for those with baseline hypertension. Conclusions This study suggests that initiation of a low dose of antihypertensive treatment does not significantly increase the risk of OH in patients with mild-to-moderate Alzheimer disease. Clinical Trial Registration URL: . Unique identifier: NCT02017340.

Hypertension ; 72(1): 139-150, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29844143


Cerebral autoregulation and baroreflex sensitivity are key mechanisms that maintain cerebral blood flow. This study assessed whether these control mechanisms are affected in patients with dementia and mild cognitive impairment due to Alzheimer disease, as this would increase the risks of antihypertensive treatment. We studied 53 patients with dementia (73.1 years [95% confidence interval (CI), 71.4-74.8]), 37 patients with mild cognitive impairment (69.2 years [95% CI, 66.4-72.0]), and 47 controls (69.4 years [95% CI, 68.3-70.5]). Beat-to-beat blood pressure (photoplethysmography), heart rate, and cerebral blood flow velocity (transcranial Doppler) were measured during 5-minute rest (sitting) and 5 minutes of orthostatic challenges, using repeated sit-to-stand maneuvers. Cerebral autoregulation was assessed using transfer function analysis and the autoregulatory index. Baroreflex sensitivity was estimated with transfer function analysis and by calculating the heart rate response to blood pressure changes during the orthostatic challenges. Dementia patients had the lowest cerebral blood flow velocity (P=0.004). During rest, neither transfer function analysis nor the autoregulatory index indicated impairments in cerebral autoregulation. During the orthostatic challenges, higher autoregulatory index (P=0.011) and lower transfer function gain (P=0.017), indicating better cerebral autoregulation, were found in dementia (4.56 arb. unit [95% CI, 4.14-4.97]; 0.59 cm/s per mm Hg [95% CI, 0.51-0.66]) and mild cognitive impairment (4.59 arb. unit [95% CI, 4.04-5.13]; 0.51 cm/s per mm Hg [95% CI, 0.44-0.59]) compared with controls (3.71 arb. unit [95% CI, 3.35-4.07]; 0.67 cm/s per mm Hg [95% CI, 0.59-0.74]). Baroreflex sensitivity measures did not differ between groups. In conclusion, the key mechanisms to control blood pressure and cerebral blood flow are not reduced in 2 stages of Alzheimer disease compared with controls, both in rest and during orthostatic changes that reflect daily life challenges.

Doença de Alzheimer/fisiopatologia , Velocidade do Fluxo Sanguíneo/fisiologia , Pressão Sanguínea/fisiologia , Circulação Cerebrovascular/fisiologia , Artéria Cerebral Média/fisiopatologia , Idoso , Barorreflexo/fisiologia , Teste de Esforço , Feminino , Seguimentos , Homeostase/fisiologia , Humanos , Masculino , Artéria Cerebral Média/diagnóstico por imagem , Estudos Retrospectivos , Ultrassonografia Doppler Transcraniana