Live long and PROSPERO: A comment on Chiu and coworkers

The a priori registration of systematic reviews provides a way to describe the methods for a meta-analysis before Review Paper selection commences. Chiu and coworkers report a systematic review of blood pressure variability, deviating from the protocol registered on PROSPERO (CRD42020190429)

Blood Pressure Variability and Progression of Clinical Alzheimer Disease

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) mmHg 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: β, 2.24 [95% CI, 0.11–4.38], P=0.040; diastolic: β, 2.54 [95% CI, 0.33–4.75] P=0.024). This association was still present after 1.5 years (systolic: β, 2.86 [95% CI, 0.35–5.36], P=0.026; diastolic: β, 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

Day-to-Day Home Blood Pressure Variability is Associated with Cerebral Small Vessel Disease Burden in a Memory Clinic Population

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

Capturing postural blood pressure dynamics with near-infrared spectroscopy-measured cerebral oxygenation

Orthostatic hypotension (OH) is highly prevalent in older adults and associated with dizziness, falls, lower physical and cognitive function, cardiovascular disease, and mortality. OH is currently diagnosed in a clinical setting with single-time point cuff measurements. Continuous blood pressure (BP) devices can measure OH dynamics but cannot be used for daily life monitoring. Near-infrared spectroscopy (NIRS) has potential diagnostic value in measuring cerebral oxygenation continuously over a longer time period, but this needs further validation. This study aimed to compare NIRS-measured (cerebral) oxygenation with continuous BP and transcranial Doppler-measured cerebral blood velocity (CBv) during postural changes. This cross-sectional study included 41 participants between 20 and 88 years old. BP, CBv, and cerebral (long channels) and superficial (short channels) oxygenated hemoglobin (O2Hb) were measured continuously during various postural changes. Pearson correlations between BP, CBv, and O2Hb were calculated over curves and specific characteristics (maximum drop amplitude and recovery). BP and O2Hb only showed good curve-based correlations (0.58–0.75) in the initial 30 s after standing up. Early (30–40 s) and 1-min BP recovery associated significantly with O2Hb, but no consistent associations were found for maximum drop amplitude and late (60–175 s) recovery values. Associations between CBv and O2Hb were poor, but stronger for long-channel than short-channel measurements. BP associated well with NIRS-measured O2Hb in the first 30 s after postural change. Stronger associations for CBv with long-channel O2Hb suggest that long-channel NIRS specifically reflects cerebral blood flow during postural transitions, necessary to better understand the consequences of OH such as intolerance symptoms

Correction to: Capturing postural blood pressure dynamics with near‑infrared spectroscopy‑measured cerebral oxygenation (GeroScience, (2023), 10.1007/s11357-023-00791-9)

In the article version originally published online, Table 2 was switched in the publication process. The correct version of Table 2 is shown below. (Table presented.) Heat map of average correlations for supine-stand and sit-stand transitions, during initial response (0-30 seconds after standing up) and late response (30-175 seconds after standing up) * Significantly different (p<0.05) between O2Hb-l and O2Hb-s. SBP Systolic blood pressure; DBP Diastolic blood pressure; MCAv Mean cerebral blood velocity in the middle cerebral artery; O2Hb-l Oxygenated hemoglobin measured with long channels; O2Hb-s Oxygenated hemoglobin measured with short channels; HHb-l Deoxygenated hemoglobin measured with long channels; HHb-s Deoxygenated hemoglobin measured with short channels

Clinical aspects of a large group of adults with Angelman syndrome

Descriptions of the clinical features of Angelman syndrome (AS) have mainly been focused on children. Here, we describe the evolution of the clinical phenotypes of AS in adulthood, using clinical data from 95 individuals (mean age 31.6 years, median 29.0 years, range 18–83 years), with genetically confirmed AS. Data was collected through physical examination and inspection of medical records, combined with questionnaires and interviews. Adults with AS experience substantial debilitating health problems. Constipation, reflux, visual problems, scoliosis, behavioral and sleeping problems occurred frequently and require appropriate attention. Epilepsy was reported in 57% of adults, negatively affecting the level of functioning. Non-convulsive status epilepticus was not observed in the adults, however some individuals developed prolonged episodes of rhythmic shaking while awake. A decline in mobility was noted in the majority of adults. A minority of adults with AS showed microcephaly. Taken together, this first phenotypic study of adults with AS to include in person interviews with care-givers and physical examination of patients, including the eldest adult reported to date, provides important insight in the development of the syndrome into adulthood. This knowledge is required to improve care for adult individuals with AS and to evaluate future therapies for this group

CSTB NULL MUTATION ASSOCIATED WITH MICROCEPHALY, EARLY DEVELOPMENTAL DELAY, AND SEVERE DYSKINESIA

The CSTB gene encodes for cystatin B, an inhibitor of lysosomal cysteine protease (cathepsins B, H, L, and S).(CSTB)-C-1 mutations have been associated with type 1 progressive myoclonic epilepsy, also known as Unverricht-Lundborg (ULD) disease, or Baltic myoclonus.(2,3) A total of 90% of all disease alleles consists of an expansion of at least 30 times of an unstable 12-nucleotide stretch (dodecamer 5-CCCCGCCCCGCG-3) in the CSTB promoter region. Homozygosity for this expansion is considered the founder mutation in the Finnish population. Few other mutations have been described, among these the p.Arg68*, but until now only as compound heterozygous with the dodecamer expansion.(4-6) Expression of the p.Arg68* mutation in vitro indicates that the truncated protein is rapidly degraded, confirming that it is a null mutation.(7) Between the ages of 6 and 16 years, ULD begins with stimulus-sensitive myoclonus and generalized tonic-clonic seizures, which can be worsened by phenytoin, followed by ataxia and slow neurodegeneration. Here we report on the first 2 patients with a homozygous p.Arg68* null mutation

Association Between Blood Pressure Variability With Dementia and Cognitive Impairment: A Systematic Review and Meta-Analysis

Research links high blood pressure variability (BPV) with stroke and cerebrovascular disease, however, its association with cognition remains unclear. Moreover, it remains uncertain which BP-derived parameter (ie, variability or mean) holds more significance in understanding vascular contributions to cognitive impairment. We searched PubMed, Embase, PsycINFO, and Scopus and performed a meta-analysis of studies that quantified the association between resting BPV with dementia or cognitive impairment in adults. Two authors independently reviewed all titles, abstracts, and full-texts and extracted data, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-Analysis of Observational Studies in Epidemiology guidelines. Study quality was assessed using the (modified) Newcastle-Ottawa Scale. A multilevel meta-analysis was used, which included effect sizes for both BPV and mean BP, with a combined end point of dementia or cognitive impairment as primary outcome. In the primary analysis, 54 effect sizes were extracted from 20 studies, with a total analytical sample of n=7 899 697. Higher systolic BPV (odds ratio [OR], 1.25 [95% CI, 1.16-1.35]), mean systolic pressure (OR, 1.12 [95% CI, 1.02-1.29]), diastolic BPV (OR, 1.20 [95% CI, 1.12-1.29]), and mean diastolic pressure (OR, 1.16 [95% CI, 1.04-1.29]) were associated with dementia and cognitive impairment. A direct comparison showed that mean BP effect sizes were less strong than BPV effect sizes (OR, 0.92 [95% CI, 0.87-0.97],

Association Between Blood Pressure Variability With Dementia and Cognitive Impairment: A Systematic Review and Meta-Analysis

Research links high blood pressure variability (BPV) with stroke and cerebrovascular disease, however, its association with cognition remains unclear. Moreover, it remains uncertain which BP-derived parameter (ie, variability or mean) holds more significance in understanding vascular contributions to cognitive impairment. We searched PubMed, Embase, PsycINFO, and Scopus and performed a meta-analysis of studies that quantified the association between resting BPV with dementia or cognitive impairment in adults. Two authors independently reviewed all titles, abstracts, and full-texts and extracted data, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-Analysis of Observational Studies in Epidemiology guidelines. Study quality was assessed using the (modified) Newcastle-Ottawa Scale. A multilevel meta-analysis was used, which included effect sizes for both BPV and mean BP, with a combined end point of dementia or cognitive impairment as primary outcome. In the primary analysis, 54 effect sizes were extracted from 20 studies, with a total analytical sample of n=7 899 697. Higher systolic BPV (odds ratio [OR], 1.25 [95% CI, 1.16-1.35]), mean systolic pressure (OR, 1.12 [95% CI, 1.02-1.29]), diastolic BPV (OR, 1.20 [95% CI, 1.12-1.29]), and mean diastolic pressure (OR, 1.16 [95% CI, 1.04-1.29]) were associated with dementia and cognitive impairment. A direct comparison showed that mean BP effect sizes were less strong than BPV effect sizes (OR, 0.92 [95% CI, 0.87-0.97], P<0.01), indicating that the relative contribution of BPV exceeded that of mean BP. Methodological and statistical heterogeneity was high. Secondary analyses were less consistent as to whether BPV and mean BP were differentially associated with dementia subtypes and cognitive domains. Future studies are required to investigate BPV as a target for dementia prevention