Abstract Objective: We analyzed cross-sectional data from a cohort of 90+ year-olds to test the hypothesis that BP variables are associated with cognitive function and cerebral microbleeds (CMB). Background: Multiple studies suggest a role for blood pressure (BP) variability and nocturnal BP dipping in the development of cerebrovascular disease and cognitive impairment. Design/Methods: Study subjects were 121 participants (mean age = 93 years, 63% female) in The 90+Study, a study of aging in individuals aged 90 years and older from a California retirement community and surrounding area. Participants were given a neuropsychological test battery and a neurological exam to determine cognitive status. All subjects underwent 24-hour ambulatory BP measurement with a fully automatic device. MRI scans were available for 26 participants. Over three time frames (24-hour, daytime, nighttime) and separately for SBP and DBP, we represented BP by mean, minimum, maximum, standard deviation (SD), coefficient of variation, average real variability, percentage of high measurements (≥140 mmHg for SBP and ≥90 mmHg for DBP), percentage of low measurements (<90 mm Hg for SBP and <60 mmHg for DBP), and nocturnal dip (% change of mean night BP from mean day BP). Differences in means of BP variables between groups based on cognitive status (normal vs cognitively impaired not demented (CIND)/demented)and presence/absence of CMB were tested using t-tests. Results: Cognitive status was normal in 97 subjects, CIND/demented in 24. Mean nocturnal dips (both SBP and DBP) differed significantly between the two groups, with normal participants having on average greater dip levels (6.6 vs 1.3, p=0.006 for SBP and 11 vs 4.4, p=0.002for DBP). No other BP variable showed a large or significant difference. Conclusions: Among 90+ year olds, nocturnal BP dipping may have a role in cognitive impairment, while SBP variation and diastolic hypertension may contribute to development of microbleeds.

We present a case of an otherwise healthy 20-month-old with congenital sensorineural hearing loss. CT and MR imaging demonstrated bilateral asymmetrically severe hypoplasia of the internal auditory canals and vestibulocochlear nerves. Additional developmental inner ear anomalies were present in this patient, including unilateral semicircular canal hypoplasia and suspected bilateral cochlear hypoplasia. The patient retained normal facial nerve function bilaterally. We highlight the current research and understanding of congenital IAC abnormalities.

We present a case of an otherwise healthy 20-month-old with congenital sensorineural hearing loss. CT and MR imaging demonstrated bilateral asymmetrically severe hypoplasia of the internal auditory canals and vestibulocochlear nerves. Additional developmental inner ear anomalies were present in this patient, including unilateral semicircular canal hypoplasia and suspected bilateral cochlear hypoplasia. The patient retained normal facial nerve function bilaterally. We highlight the current research and understanding of congenital IAC abnormalities.

Introduction: Multiple studies suggest a role for blood pressure (BP) variability and nocturnal BP dipping in the development of cerebrovascular disease and cognitive impairment. We analyzed cross-sectional data from a cohort of 90+ year-olds to test the hypothesis that BP variables are associated with cognitive function and cerebral microbleeds (CMB). Methods: Study subjects were 121 participants (mean age = 93 years, 63% female) in The 90+ Study, a study of aging in individuals aged 90 years and older from a California retirement community. Participants were given a neuropsychological test battery to determine cognitive status. All subjects underwent 24-hour ambulatory BP measurement with a automatic device. MRI scans were available for 26 participants. Over three time frames (24-hour, daytime, nighttime) and separately for SBP and DBP, we represented BP by mean, minimum, maximum, standard deviation (SD), coefficient of variation, average real variability, percentage of high measurements (≥140 mmHg for SBP and ≥90 mmHg for DBP), percentage of low measurements (<90 mmHg for SBP and <60 mmHg for DBP), and nocturnal dip (% change of mean night BP from mean day BP). Differences in means of BP variables between groups based on cognitive status (normal vs cognitively impaired not demented (CIND)/demented) and presence/absence of CMB were tested using t-tests. Results: Cognitive status was normal in 97 subjects, CIND/demented in 24. Mean nocturnal dips (both SBP and DBP) differed significantly between the two groups, with normal participants having on average greater dip levels (6.6 vs 1.3, p=0.006 for SBP and 11 vs 4.4, p=0.002 for DBP). No other BP variable showed a large or significant difference. Greater nocturnal dips were also related to better performance on cognitive test scores related to language, recent memory, and visual-spatial ability. MRI findings showed subjects with CMB (n=18) had higher SD of daytime SBP than those without (n=8) (20 vs 16, p=0.03). Those with CMB also had a greater proportion of high nighttime DBP (≥90 mmHg) readings (3.6 vs 0, p=0.03). Conclusions: Among 90+ year olds, altered nocturnal BP dipping may have a role in cognitive impairment, while SBP variation and diastolic hypertension may contribute to development of microbleeds.

Objective

To characterize the prevalence of brain ischemia and cerebral small vessel disease in a cohort of patients with Fabry disease (FD) seen at an academic medical center.

Background

FD is an inherited X-linked lysosomal storage disorder with central nervous system involvement. Limited data are available in the literature on the cerebrovascular neuroimaging findings in FD, and the reported prevalence of stroke symptoms and cerebral small vessel disease has varied widely.

Design/methods

Brain MRI was performed in 21 patients with FD followed at University of California Irvine Medical Center. Stroke symptoms were assessed and quantification of cerebral microvascular disease was performed using small vessel disease (SVD) score. Lacunes and deep white matter hyperintensities were scored on a four-point scale of 0 (absent) and 1-3 to account for increasing severity; microbleeds were scored 0 (absent) or 1 (present). The total SVD score is the sum of the three components and ranges from 0 to 7.

Results

Nearly 43% (9/21) of our FD cohort (aged 32-81 years, mean = 50) had a SVD score of one or higher, all of whom were aged 50 or more years. The most common MRI-defined SVD was white matter hyperintensities (9/9, 100%), followed by microbleeds (6/9, 66%), and lacunes (3/9, 33%). The three patients with previous strokes had some of the highest SVD scores reported in the cohort (scores 3-5).

Conclusions

In this cohort, the prevalence of SVD (43%) was three times higher than prevalence of stroke symptoms. SVD score was highest in the those who had experienced a stroke. These findings emphasize the importance of routine MRI screening of patients with FD in order to identify and treat high risk patients.

The objective of this study is to assess the effectiveness of a stroke clinic in stroke prevention and progression of cerebral microbleeds (CMB). We conducted a retrospective observational study of patients who visited a stroke clinic between January 2011 and March 2017. Susceptibility-weighted imaging (SWI) MRI studies were obtained at baseline and follow-up visits to identify new infarctions and CMB progression. Patients with CMB who also underwent brain computed tomography (CT) imaging were identified and their cerebral arterial calcification was quantified to evaluate the relationship between the extent of intracranial calcification and CMB burden. A total of 64 stroke patients (mean age 73.1 ± 11.0, 47% males) had CMB on baseline and follow-up MRI studies. During a mean follow-up period of 22.6 months, four strokes occurred (4/64, 6%; 3 ischemic, 1 hemorrhagic), producing mild neurological deficit. Progression of CMB was observed in 54% of patients with two MRIs and was significantly associated with length of follow-up. Subjects with intracranial calcification score > 300 cm³ had higher CMB count than those with scores <300 cm³ at both baseline (12.6 ± 11.7 vs. 4.9 ± 2.2, p = 0.02) and follow-up (14.1 ± 11.8 vs. 5.6 ± 2.4, p = 0.03) MRI evaluations. Patients with CMB had a relatively benign overall clinical course. The association between CMB burden and intracranial calcification warrants further study.

Purpose: To analyze the relationship between blood pressure (BP) variables, including circadian pattern, and cognition in 90+ year-olds. Methods: Twenty-four hour ambulatory BP monitoring was completed on 121 participants drawn from a longitudinal study of aging and dementia in the oldest-old. Various measures of BP and its variability, including nocturnal dipping, were calculated. Each person was given both a neuropsychological test battery covering different cognitive domains and a neurological examination to determine cognitive status. Seventy-one participants had a brain magnetic resonance imaging (MRI) scan. Results: Participants ranged in age from 90 to 102 years (mean = 93), about two-thirds were female, and nearly 80% had at least some college education. Mean nocturnal dips differed significantly between cognitively normal (n = 97) and impaired individuals (n = 24), with cognitively normal participants having on average greater nocturnal dips [6.6% vs. 1.3%, p = 0.006 for systolic BP (SBP); 11% vs. 4.4%, p = 0.002 for diastolic BP (DBP)]. Nocturnal dips were also related to performance on select cognitive test scores (especially those related to language, recent memory and visual-spatial ability), with individuals who performed below previously established median norms having significantly smaller nocturnal dips (both SBP and DBP) than those above the median. DBP reverse dippers had larger mean white matter hyperintensities (WMH as percent of total brain volume; 1.7% vs. 1.2%, 1.1% and 1.0% in extreme dippers, dippers, non-dippers) and a greater proportion had lobar cerebral microbleeds (CMBs; 44% vs. 0%, 7%, 16%, p < 0.05). Impaired participants had higher mean WMH than those with normal cognition (1.6% vs. 1.0% p = 0.03) and more tended to have CMB (31% vs. 20%, p = n.s.). Conclusion: These findings suggest that cognitive dysfunction is associated with dysregulation in the normal circadian BP pattern. Further study is warranted of the potential role of WHM and CMB as mediators of this association.

Background

Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common genetic cause of stroke. In addition to ischemic stroke, CADASIL predisposes to development of cerebral microbleeds (CMB). CMB and hypertension are known to be associated with intracerebral hemorrhage (ICH). The purpose of this study was to analyze the relationships among CMB, hypertension, and ICH in CADASIL.

Materials and methods

We enrolled 94 genetically confirmed CADASIL patients from 76 unrelated families at Jeju National University Hospital (Korea) between March 2012 and February 2015. We analyzed CMB presence, number, and distribution on susceptibility-weighted imaging MRI using the microbleed anatomical rating scale. Multiple logistic regression was used to determine factors associated with the presence of CMB and ICH.

Results

CMB were observed in 62 patients (66%), median number of CMB per patient was 4 (range 0-121). Twenty-two ICHs were found in 16 patients (17%). There was incongruence between the most common site of CMB (thalamus) and that of ICH (basal ganglia). Hypertension was independently associated with the presence of CMB (multiple regression OR, 2.71; 95% CI 1.02-7.18, p < 0.05), and CMB ≥ 9 (highest third) was significantly associated with the presence of ICH (multiple regression OR = 9.50, 95% CI 1.08-83.71, p < 0.05).

Conclusion

In this CADASIL sample, presence of hypertension was independently associated with CMB presence, and CMB burden was independently associated with ICH. Incongruence of sites for CMB and ICH is currently unexplained and requires further study.

Chronic kidney disease is emerging as a novel risk factor for cerebrovascular disease, but this association remains largely unexplored in older adults. Cystatin C is a more accurate measure than creatinine of kidney function in the elderly. We evaluated cystatin C, cognitive function, and brain imaging in 193 participants from The 90+ Study neuroimaging component. The mean age was 93.9 years; 61% were women. Mean cystatin C was 1.62 mg/L with estimated glomerular filtration rate 39.2 mL/min/1.73 m². Performance on measures of global cognition, executive function, and visual-spatial ability declined at higher tertiles of cystatin C (lower kidney function). Higher cystatin C was significantly associated with infratentorial microbleeds and lower gray matter volume. Adjusted risk of incident dementia was increased in the middle and high cystatin C tertile groups compared with the low group (hazard ratio in highest tertile 3.81 [95% confidence interval 1.14-12.7]), which appeared to be explained in part by the presence of cerebral microbleeds. Overall, cystatin C was associated with cognitive performance, brain imaging pathology, and decline to dementia in this oldest-old cohort.

Background

Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common genetic cause of stroke. In addition to ischemic stroke, CADASIL predisposes to development of cerebral microbleeds (CMB). CMB and hypertension are known to be associated with intracerebral hemorrhage (ICH). The purpose of this study was to analyze the relationships among CMB, hypertension, and ICH in CADASIL.

Materials and methods

We enrolled 94 genetically confirmed CADASIL patients from 76 unrelated families at Jeju National University Hospital (Korea) between March 2012 and February 2015. We analyzed CMB presence, number, and distribution on susceptibility-weighted imaging MRI using the microbleed anatomical rating scale. Multiple logistic regression was used to determine factors associated with the presence of CMB and ICH.

Results

CMB were observed in 62 patients (66%), median number of CMB per patient was 4 (range 0-121). Twenty-two ICHs were found in 16 patients (17%). There was incongruence between the most common site of CMB (thalamus) and that of ICH (basal ganglia). Hypertension was independently associated with the presence of CMB (multiple regression OR, 2.71; 95% CI 1.02-7.18, p < 0.05), and CMB ≥ 9 (highest third) was significantly associated with the presence of ICH (multiple regression OR = 9.50, 95% CI 1.08-83.71, p < 0.05).

Conclusion

In this CADASIL sample, presence of hypertension was independently associated with CMB presence, and CMB burden was independently associated with ICH. Incongruence of sites for CMB and ICH is currently unexplained and requires further study.