Robust reference group normative data for neuropsychological tests accounting for primary language use in Asian American older adults.

OBJECTIVE: The present study aimed to develop neuropsychological norms for older Asian Americans with English as a primary or secondary language, using data from the National Alzheimer's Coordinating Center (NACC). METHOD: A normative sample of Asian American participants was derived from the NACC database using robust criteria: participants were cognitively unimpaired at baseline (i.e., no MCI or dementia) and remained cognitively unimpaired at 1-year follow-up. Clinical and demographic characteristics were compared between Primary and Secondary English speakers using analyses of variance for continuous measures and chi-square tests for categorical variables. Linear regression models compared neuropsychological performance between the groups, adjusting for demographics (age, sex, and education). Regression models were developed for clinical application to compute demographically adjusted z-scores. RESULTS: Secondary English speakers were younger than Primary English speakers (p < .001). There were significant differences between the groups on measures of mental status (Mini-Mental State Examination, p = .002), attention (Trail Making Test A, Digit Span Forward Total Score, p <.001), language (Boston Naming Test, Animal Fluency, Vegetable Fluency, p < .001), and executive function (Trail Making Test B, p = .02). CONCLUSIONS: Separate normative data are needed for Primary vs. Secondary English speakers from Asian American backgrounds. We provide normative data on older Asian Americans to enable clinicians to account for English use in the interpretation of neuropsychological assessment scores.

Smart mandibular advancement devices for obstructive sleep apnea: a systematic literature review.

PURPOSE: The goal of this review is to provide sleep physicians, dentists, and researchers with an evidence-based overview of the literature on smart mandibular advancement devices (MADs) for the treatment of obstructive sleep apnea. METHODS: A systematic literature search was conducted by two blinded reviewers and an information specialist. A smart MAD was defined as any MAD with additional functionality besides mandibular protrusion. The bibliographic databases Medline, Embase, and Scopus were used to identify relevant publications. Studies were included if they described any stage of development of smart MADs. A total of 3162 titles and abstracts were screened for their relevance. In total, 58 articles were selected for full-text screening, 26 of which were included in this review. RESULTS: The overall quality of the available literature was low. Most of the studies were observational, clinical or applied-research articles. The authors classified MADs into two main groups: passive and active. Passive MADs measured patient data, most commonly patient compliance. Active MADs adjusted protrusion of the mandible in response to patient data and were found in various phases of technological readiness (in development, demonstration, or deployment). CONCLUSION: Innovations in smart mandibular advancement devices most frequently track patient compliance. Devices measuring other health parameters and active, feedback-controlled, devices are increasingly reported on. However, studies demonstrating their added benefit over traditional methods remain sparse. With further study, smart mandibular advancement devices have the potential to improve the efficiency of obstructive sleep apnea treatment and provide new treatment possibilities.

A review and evaluation of orthodontic brackets, molar bands and orthodontic auxiliaries during orthognathic surgery: A prospective cohort study.

OBJECTIVE: The primary aim of this study was to provide a review of the types and frequency of orthodontic brackets, molar bands and orthodontic auxiliaries used for patients undergoing orthognathic surgery. The secondary aim was to evaluate the risk of failure of these items during orthognathic surgery. METHODS: From three Dutch hospitals, 124 adult patients were included in this prospective cohort study. Five independent researchers collected the data during surgery using a specifically created data extraction form. The type of surgery, surgeon, orthodontist and type of orthodontic bracket, molar band or auxiliary were noted for each tooth. To evaluate their failure risk, the following variables were noted: failure and site; and type and cause of failure. RESULTS: Stainless-steel brackets were the most frequently (75.8%) used bracket type seen in patients undergoing orthognathic surgery. Ceramic brackets were seen in 24.2% of the cases and were only applied in the anterior region. Molar bands were present in 58.9% of the patients and mostly with bands on the first molars in combination with bonded tubes on the second molars. In 32.2% of all cases, one or more failures were noted. One-third of all failures were described as detachment of the molar tube on the most posterior molar. Kobayashi ligatures and powerpins showed the highest risk of failure (odds ratio [OR] 3.70, 95% confidence interval [CI] = 1.91-7.15). No significant difference in failure rate was found between stainless-steel brackets, molar bands (OR 0.34, 95% CI = 0.08-1.43) and ceramic brackets (OR 0.44, 95% CI = 0.14-1.45). CONCLUSION: Stainless-steel brackets, ceramic brackets, molar bands and surgical hooks are suitable for orthognathic cases. Kobayashi ligatures and powerpins had a significantly higher risk of failure so are not recommended for temporary intraoperative maxillomandibular fixation (TIO-MMF).

Maxillomandibular advancement for obstructive sleep apnea: a retrospective prognostic factor study for surgical response.

PURPOSE: To identify potential predictors of surgical response to maxillomandibular advancement (MMA) in patients with obstructive sleep apnea (OSA) from the most common clinically available data (patient-related, polysomnographic, cephalometric, and surgical variables). METHODS: This was a retrospective study comprised of consecutive patients who underwent MMA for moderate to severe OSA. Relevant clinical, polysomnographic, cephalometric, and surgical variables were collected as independent variables (predictors). The association of the independent variables with a favorable surgical response to MMA was assessed in univariate and multivariate analyses. RESULTS: In 100 patients (82% male; mean age 50.5 years), the mean apnea hypopnea index [AHI] was 53.1 events/h. The rate of favorable surgical response was 67%. Based on multivariate analysis, patients with cardiovascular disease (CVD) had 0.140 times lower odds of a favorable response to MMA (OR: 0.140 [0.038, 0.513], P = 0.003). For each 1-unit increase in central apnea index (CAI) and superior posterior airway space (SPAS), there were 0.828 and 0.724 times lower odds to respond favorably to MMA (OR: 0.828 [0.687, 0.997], P = 0.047; and 0.724 [0.576, 0.910], P = 0.006), respectively. CONCLUSION: The findings of this study suggest that the surgical outcome of MMA may be less favorable when patients with OSA have certain phenotypic characteristics: the presence of CVD, higher CAI and larger SPAS. If confirmed in future studies, these variables may guide patient selection for MMA.

Older adults with perivascular spaces exhibit cerebrovascular reactivity deficits.

BACKGROUND: Perivascular spaces on brain magnetic resonance imaging (MRI) may indicate poor fluid drainage in the brain and have been associated with numerous neurological conditions. Cerebrovascular reactivity (CVR) is a marker of cerebrovascular function and represents the ability of cerebral blood vessels to regulate cerebral blood flow in response to vasodilatory or vasoconstrictive stimuli. We aimed to examine whether pathological widening of the perivascular space in older adults may be associated with deficits in CVR. METHODS: Independently living older adults free of dementia or clinical stroke were recruited from the community and underwent brain MRI. Pseudo-continuous arterial spin labeling MRI quantified whole brain cerebral perfusion at rest and during CVR to hypercapnia and hypocapnia induced by visually guided breathing exercises. Perivascular spaces were visually scored using existing scales. RESULTS: Thirty-seven independently living older adults (mean age = 66.3 years; SD = 6.8; age range 55-84 years; 29.7% male) were included in the current analysis. Multiple linear regression analysis revealed a significant negative association between burden of perivascular spaces and global CVR to hypercapnia (B = -2.0, 95% CI (-3.6, -0.4), p = .015), adjusting for age and sex. Perivascular spaces were not related to CVR to hypocapnia. DISCUSSION: Perivascular spaces are associated with deficits in cerebrovascular vasodilatory response, but not vasoconstrictive response. Enlargement of perivascular spaces could contribute to, or be influenced by, deficits in CVR. Additional longitudinal studies are warranted to improve our understanding of the relationship between cerebrovascular function and perivascular space enlargement.

Neuropsychological Profiles and Trajectories in Preclinical Alzheimer's Disease.

OBJECTIVES: The present study investigated the independent and synergistic effects of amyloid beta (Aß1-42) and phosphorylated tau (Ptau) pathologies on neuropsychological profiles and trajectories in cognitively normal older adults. METHODS: Alzheimer's Disease Neuroimaging Initiative participants identified as cognitively normal at baseline underwent longitudinal assessment (N=518; 0, 12, 24, 36 months), baseline lumbar puncture and follow-up cognitive exams. Cerebral spinal fluid (CSF) biomarker profiles (Aß-Ptau-, Aß+Ptau-, Aß-Ptau+, Aß+Ptau+) were compared on baseline profiles and trajectories for memory (Rey Auditory Verbal Learning Test), attention/executive function (Trail Making Test, A and B), language (Animal Fluency, Vegetable Fluency, Boston Naming Test) and processing speed (Digit Symbol) using multilevel models. RESULTS: The Aß+Ptau+ group exhibited significantly worse baseline performance on tests of memory and executive function relative to the Aß-Ptau+ and Aß-Ptau- groups. The Aß+Ptau- group fell between the Aß+Ptau+ participants and the Aß-Ptau- and Aß-Ptau+ groups on all three cognitive domains and exhibited worse baseline executive function. The Aß-Ptau+ group performed worse than Aß-Ptau- participants on processing speed. Over 36-month follow-up, the Aß+Ptau+ group exhibited the greatest declines in memory and semantic fluency compared to all other groups. CONCLUSIONS: Cognitively normal older adults with both Aß and Ptau pathology exhibited the weakest profile, marked by the worst memory decline compared to the other groups. Other subtle changes in this group included declines in executive function and semantic fluency. Those with Ptau pathology alone showed slowed processing speed, and those with Aß pathology alone showed worse attention and executive function compared to biomarker negative participants. (JINS, 2018, 24, 693-702).

Non-sleep related outcomes of maxillomandibular advancement, a systematic review.

Maxillomandibular advancement has been shown to be an effective treatment for obstructive sleep apnea; however, the literature focuses mainly on sleep-related parameters such as apnea-hypopnea index, respiratory disturbance index and Epworth sleepiness scale. Other factors that may be important to patients, such as esthetics, patient satisfaction, nasality, swallowing problems and so forth have been reported in the literature but have not been systematically studied. Together with an information specialist, an extensive search in Medline, Embase and Scopus yielded 1592 unique articles. Titles and abstracts were screened by two blinded reviewers. In total, 75 articles were deemed eligible for full-text screening and 38 articles were included for qualitative synthesis. The most common categories of non-sleep related outcomes found were surgical accuracy, facial esthetics, functional outcomes, quality of life, patient satisfaction, and emotional health. All categories were reported using heterogenous methods, such that meta-analysis could not be performed. There was lack of consistent methods to assess these outcomes. This work is the first to systematically review non-sleep related outcomes of maxillomandibular advancement. Despite growing interest in evaluating surgical outcomes through patient subjective experiences, this review points to the need of standardized, validated methods to report these outcomes.

Evaluation of Anti-Glycopeptidolipid-Core Immunoglobulin A Antibody Detection for the Diagnosis of Nontuberculous Mycobacterial Cervicofacial Lymphadenitis.

A multicenter cross-sectional diagnostic study was carried out including 45 children with nontuberculous mycobacterial cervicofacial lymphadenitis and controls. The tested immunoassay, detecting M. avium-specific anti-glycopeptidolipid-core immunoglobulin A antibodies, had inadequate diagnostic performance in the studied population and seems to be of no additional value in detecting cases of nontuberculous mycobacterial cervicofacial lymphadenitis.

Early root migration after a mandibular third molar coronectomy.

PURPOSE: This prospective cohort study aimed to assess early root migration after a coronectomy of the mandibular third molar at 2 and 6 months after surgery. METHODS: We included all patients treated with a coronectomy of an impacted mandibular third molar. The primary outcome measure was the extent of postoperative root migration after 2 and 6 months. Migration was measured as the distance between the root complex and a fixed point on the inferior alveolar canal. The secondary aim was to identify factors (age, impaction pattern, and patient sex) that affected the extent of root migration. RESULTS: One hundred and sixty-five coronectomies were performed in 141 patients (96 females and 45 males; mean age 33.1 years, SD 16.0). The 2-month checkup was completed by 121 patients that received 141 coronectomies. The 6-month check-up was completed by 73 patients that received 80 coronectomies. The mean root migrations were 3.30 mm (SD 2.53 mm) at 2 months and 5.27 mm (SD 3.14 mm) at 6 months. In the 2-6-month interval, the mean root migration was 2.58 mm (SD 2.07 mm). The extents of migration were similar during the 0-2-month interval and the 2-6-month interval (p = 0.529). Younger age was associated with greater root migration, and females experienced significantly greater migrations than males (p = 0.002). CONCLUSION: Roots migrated more rapidly in the first two postoperative months, compared to the 2-6-month interval. Age was negatively correlated with the extent of root migration, and females showed significantly greater migrations than males.

Development and Internal Validation of a Prediction Model for Surgical Success of Maxillomandibular Advancement for the Treatment of Moderate to Severe Obstructive Sleep Apnea.

Background: Maxillomandibular advancement (MMA) has been shown to be the most effective surgical therapy for obstructive sleep apnea (OSA). Despite high success rates, there are patients who are considered as non-responders to MMA. In order to triage and inform these patients on their expected prognosis of MMA before the surgery, this study aimed to develop, internally validate, and calibrate a prediction model for the presence of surgical success for MMA in patients with OSA. Methods: A retrospective cohort study was conducted that included patients that had undergone MMA for moderate to severe OSA. Baseline clinical, polysomnographic, cephalometric, and drug-induced sleep endoscopy findings were recorded as potential predictors. Presence or absence of surgical success was recorded as outcome. Binary logistic regression analyses were conducted to develop the model. Performance and clinical values of the model were analyzed. Results: One hundred patients were included, of which sixty-seven (67%) patients reached surgical success. Anterior lower face height (ALFH) (OR: 0.93 [0.87−1.00], p = 0.05), superior posterior airway space (SPAS) (OR: 0.76 [0.62−0.92], p < 0.05), age (OR: 0.96 [0.91−1.01], p = 0.13), and a central apnea index (CAI) <5 events/hour sleep (OR: 0.16 [0.03−0.91], p < 0.05) were significant independent predictors in the model (significance level set at p = 0.20). The model showed acceptable discrimination with a shrunken area under the curve of 0.74, and acceptable calibration. The added predictive values for ruling in and out of surgical success were 0.21 and 0.32, respectively. Conclusions: Lower age at surgery, CAI < 5 events/hour, lower ALFH, and smaller SPAS were significant predictors for the surgical success of MMA. The discrimination, calibration, and clinical added values of the model were acceptable.

Development and external validation of prediction models for critical outcomes of unvaccinated COVID-19 patients based on demographics, medical conditions and dental status.

Background: Multiple prediction models were developed for critical outcomes of COVID-19. However, prediction models using predictors which can be easily obtained in clinical practice and on dental status are scarce. Aim: The study aimed to develop and externally validate prediction models for critical outcomes of COVID-19 for unvaccinated adult patients in hospital settings based on demographics, medical conditions, and dental status. Methods: A total of 285 and 352 patients from two hospitals in the Netherlands were retrospectively included as derivation and validation cohorts. Demographics, medical conditions, and dental status were considered potential predictors. The critical outcomes (death and ICU admission) were considered endpoints. Logistic regression analyses were used to develop two models: for death alone and for critical outcomes. The performance and clinical values of the models were determined in both cohorts. Results: Age, number of teeth, chronic kidney disease, hypertension, diabetes, and chronic obstructive pulmonary diseases were the significant independent predictors. The models showed good to excellent calibration with observed: expected (O:E) ratios of 0.98 (95%CI: 0.76 to 1.25) and 1.00 (95%CI: 0.80 to 1.24), and discrimination with shrunken area under the curve (AUC) values of 0.85 and 0.79, based on the derivation cohort. In the validation cohort, the models showed good to excellent discrimination with AUC values of 0.85 (95%CI: 0.80 to 0.90) and 0.78 (95%CI: 0.73 to 0.83), but an overestimation in calibration with O:E ratios of 0.65 (95%CI: 0.49 to 0.85) and 0.67 (95%CI: 0.52 to 0.84). Conclusion: The performance of the models was acceptable in both derivation and validation cohorts. Number of teeth was an additive important predictor of critical outcomes of COVID-19. It is an easy-to-apply tool in hospitals for risk stratification of COVID-19 prognosis.

Subjective Efficiency Evaluation after Maxillomandibular Advancement Surgery in Obstructive Sleep Apnea Patients.

PURPOSE: To investigate subjective efficiency outcomes after maxillomandibular advancement (MMA) surgery in obstructive sleep apnea (OSA) patients. MATERIAL AND METHODS: A prospective cohort study was carried out between December 2016 and May 2021, including 30 severe or treatment-refractory OSA patients treated by MMA surgery. All patients answered four validated questionnaires: the Epworth Sleepiness Scale (ESS), Functional Outcomes of Sleep Questionnaire (FOSQ), Mandibular Function Impairment Questionnaire (MFIQ), and EQ-5D-3L (i.e., EQ-5D and EQ-VAS). They also answered one custom-made questionnaire (AMCSQ). Questionnaires were requested to be filled out 1 week before surgery and at least 6 months after surgery. RESULTS: The total preoperative and postoperative scores on the questionnaires were compared. The mean total ESS (p < 0.01), FOSQ (p < 0.01), EQ-5D (p < 0.05), and EQ-VAS (p < 0.01) scores showed significant improvement, which was in accordance with an improvement in the mean postoperative apnea/hypopnea index score (p < 0.01). In contrast, the mean total MFIQ score (p < 0.01) indicated a decline in mandibular function. CONCLUSION: This study confirms the hypothesis that MMA surgery in OSA patients improves outcomes, both objectively and subjectively, with the exception of postoperative mandibular function.

Assessment of Surgical Accuracy in Maxillomandibular Advancement Surgery for Obstructive Sleep Apnea: A Preliminary Analysis.

This retrospective study aimed to: (1) investigate the surgical accuracy of maxillomandibular advancement (MMA) in obstructive sleep apnea (OSA) patients, with a specific focus on maxillary and mandibular advancement and counter-clockwise rotation and (2) investigate the correlation between the amount of achieved advancement and the reduction in the relative apnea hypopnea index (AHI). Sixteen patients, for whom a three-dimensional virtual surgical plan was generated preoperatively and a computed tomography scan (CT) or cone-beam computer tomography (CBCT) was acquired postoperatively, were included. The postoperative CT or CBCT was compared to the virtual surgical plan, and differences in the mandibular and maxillary advancement and counter-clockwise rotation were assessed. Maxillary and mandibular advancement (median 3.1 mm, p = 0.002 and 2.3 mm, p = 0.03, respectively) and counter-clockwise rotation (median 3.7°, p = 0.006 and 4.7°, p = 0.001, respectively) were notably less than intended. A significant correlation was found between the planned maxillary advancement and the difference between the planned and actual maxillary advancement (p = 0.048; adjusted R2 = 0.1979) and also between the planned counter-clockwise rotation and the difference between the planned and actual counter-clockwise rotation for the mandible (p = 0.012; adjusted R2 = 0.3261). Neither the maxilla-first nor the mandible-first surgical sequence proved to be superior in terms of the ability to achieve the intended movements (p > 0.45). Despite a significant reduction (p = 0.001) in the apnea hypopnea index (AHI) from a median of 62.6 events/h to 19.4 events/h following MMA, no relationship was found between the extent of maxillary or mandibular advancement and AHI improvement in this small cohort (p = 0.389 and p = 0.387, respectively). This study underlines the necessity for surgeons and future research projects to be aware of surgical inaccuracies in MMA procedures for OSA patients. Additionally, further research is required to investigate if sufficient advancement is an important factor associated with MMA treatment outcome.

Influence of Surgeon Experience on Surgical Outcome of Maxillomandibular Advancement for Obstructive Sleep Apnea.

The primary aim of this study was to assess the association between clinical efficacy outcomes (i.e., polysomnography (PSG) results) of maxillomandibular advancement (MMA) and surgeons' experience. The second aim was to assess the association between the occurrence of postoperative complications of MMA and surgeons' experiences. Patients treated with MMA for moderate to severe obstructive sleep apnea (OSA) were enrolled in this retrospective study. The patient population was divided into two groups based on two different surgeons performing MMA. The associations between surgeons' experience on the one hand and PSG results and postoperative complications on the other hand were investigated. A total of 75 patients were included. There was no significant difference in baseline characteristics between the two groups. The reductions in apnea-hypopnea index and oxygen desaturation index were both significantly greater in group-B than group-A (p = 0.015 and 0.002, respectively). The overall success rate after MMA was 64.0%. There was a negative correlation between surgeon experience and surgical success (odds ratio: 0.963 [0.93, 1.00], p = 0.031). No significant association was found between surgeon experience and surgical cure. Additionally, there was no significant association between surgeon experience and the occurrence of postoperative complications. Within the limitations of this study, it is concluded that surgeon experience may have little to no influence on the clinical efficacy and safety of MMA surgery in OSA patients.

Temporomandibular Joint Prosthesis in a Patient with Congenital Infiltrating Lipomatosis of the Face with Bony Ankylosis of the Temporomandibular Joint: A Case Report.

Hemifacial hyperplasia (HFH) is a rare congenital disorder characterized by marked unilateral overgrowth of the facial tissues. A subtype of HFH is congenital infiltrating lipomatosis of the face (CIL-F). This disease is characterized by unilateral diffuse infiltration of mature adipose cells in the facial soft tissue and is associated with skeletal hypertrophy. This work aims to report a case of a CIL-F patient with right facial asymmetry and progressive growth at adolescent age, causing mandibular asymmetry due to signs of concomitant unilateral condylar hyperplasia. At the age of seventeen, a condylectomy was performed to stop the progression of asymmetric mandibular growth. Five years later, the patient developed CIL-F-associated temporomandibular joint ankylosis, manifesting as progressive restricted mouth opening along with temporal facial pain. In this CIL-F patient, a TMJ reconstruction with an alloplastic total joint prosthesis was successfully performed with optimal maximal mouth opening, complete alleviation of temporal facial pain, and stable dental occlusion one year postoperatively. A TMJ reconstruction with a complete alloplastic total joint prosthesis proved to be a predictable, stable, and safe treatment option in a patient with CIL-F-associated TMJ ankylosis who was previously treated with condylectomy due to progressive mandibular asymmetry.

Intraoperative Visualization and Treatment of Salivary Gland Dysfunction in Sjögren's Syndrome Patients Using Contrast-Enhanced Ultrasound Sialendoscopy (CEUSS).

In sialendoscopy, ducts are dilated and the salivary glands are irrigated with saline. Contrast-enhanced ultrasound sialendoscopy (CEUSS), using microbubbles, may facilitate the monitoring of irrigation solution penetration in the ductal system and parenchyma. It is imperative to test CEUSS for its safety and feasibility in Sjögren's syndrome (SS) patients. CEUSS was performed on 10 SS patients. The primary outcomes were safety, determined by the occurrence of (serious) adverse events ((S)AEs), and feasibility. The secondary outcomes were unstimulated and stimulated whole saliva (UWS and SWS) flow rates, xerostomia inventory (XI), clinical oral dryness score, pain, EULAR Sjögren's syndrome patient reported index (ESSPRI), and gland topographical alterations. CEUSS was technically feasible in all patients. Neither SAEs nor systemic reactions related to the procedure were observed. The main AEs were postoperative pain (two patients) and swelling (two patients). Eight weeks after CEUSS, the median UWS and SWS flow had increased significantly from 0.10 to 0.22 mL/min (p = 0.028) and 0.41 to 0.61 mL/min (p = 0.047), respectively. Sixteen weeks after CEUSS, the mean XI was reduced from 45.2 to 34.2 (p = 0.02). We conclude that CEUSS is a safe and feasible treatment for SS patients. It has the potential to increase salivary secretion and reduce xerostomia, but this needs further investigation.

Blood-Derived Progenitor Cells Are Depleted in Older Adults with Cognitive Impairment: A Role for Vascular Resilience?

BACKGROUND: Depletion of blood-derived progenitor cells, including so called "early endothelial progenitor cells", has been observed in individuals with early stage Alzheimer's disease relative to matched older control subjects. These findings could implicate the loss of angiogenic support from hematopoietic progenitors or endothelial progenitors in cognitive dysfunction. OBJECTIVE: To investigate links between progenitor cell proliferation and mild levels of cognitive dysfunction. METHODS: We conducted in vitro studies of blood-derived progenitor cells using blood samples from sixty-five older adults who were free of stroke or dementia. Peripheral blood mononuclear cells from venous blood samples were cultured in CFU-Hill media and the number of colony forming units were counted after 5 days in vitro. Neuropsychological testing was administered to all participants. RESULTS: Fewer colony forming units were observed in samples from older adults with a Clinical Dementia Rating global score of 0.5 versus 0. Older adults whose samples developed fewer colony forming units exhibited worse performance on neuropsychological measures of memory, executive functioning, and language ability. CONCLUSION: These data suggest blood progenitors may represent a vascular resilience marker related to cognitive dysfunction in older adults.

Older Adults With Higher Blood Pressure Variability Exhibit Cerebrovascular Reactivity Deficits.

BACKGROUND: Elevated blood pressure (BP) variability is predictive of increased risk for stroke, cerebrovascular disease, and other vascular brain injuries, independent of traditionally studied average BP levels. However, no studies to date have evaluated whether BP variability is related to diminished cerebrovascular reactivity, which may represent an early marker of cerebrovascular dysfunction presaging vascular brain injury. METHODS: The present study investigated BP variability and cerebrovascular reactivity in a sample of 41 community-dwelling older adults (mean age 69.6 [SD 8.7] years) without a history of dementia or stroke. Short-term BP variability was determined from BP measurements collected continuously during a 5-minute resting period followed by cerebrovascular reactivity during 5-minute hypocapnia and hypercapnia challenge induced by visually guided breathing conditions. Cerebrovascular reactivity was quantified as percent change in cerebral perfusion by pseudo-continuous arterial spin labeling (pCASL)-MRI per unit change in end-tidal CO2. RESULTS: Elevated systolic BP variability was related to lower whole brain cerebrovascular reactivity during hypocapnia (ß = -0.43 [95% CI -0.73, -0.12]; P = 0.008; adjusted R2 =.11) and hypercapnia (ß = -0.42 [95% CI -0.77, -0.06]; P = 0.02; adjusted R2 = 0.19). CONCLUSIONS: Findings add to prior work linking BP variability and cerebrovascular disease burden and suggest BP variability may also be related to prodromal markers of cerebrovascular dysfunction and disease, with potential therapeutic implications.

Enlarged perivascular spaces and plasma Aß42/Aß40 ratio in older adults without dementia.

Dilation of perivascular spaces (PVS) in the brain may indicate poor fluid drainage due to the accumulation of perivascular cell debris, waste, and proteins, including amyloid-beta (Aß). No prior study has assessed whether plasma Aß levels are related to PVS in older adults without dementia. Independently living older adults (N = 56, mean age = 68.2 years; Standard deviation (SD) = 6.5; 30.4% male) free of dementia or clinical stroke were recruited from the community and underwent brain MRI and venipuncture. PVS were qualitatively scored and dichotomized to low PVS burden (scores 0-1,) or high PVS burden (score>1). Plasma was assayed using a Quanterix Simoa Kit to quantify Aß42 and Aß40 levels. A significant difference was observed in plasma Aß42/Aß40 ratio between low and high PVS burden, controlling for age (F[1, 53] = 5.59, p = 0.022, η2 = 0.10), with lower Aß42/Aß40 ratio in the high PVS burden group. Dilation of PVS is associated with a lower plasma Aß42/Aß40 ratio, which may indicate higher cortical amyloid deposition. Future longitudinal studies examining PVS changes, and the pathogenesis of AD are warranted.

Neuropsychological Decline Stratifies Dementia Risk in Cognitively Unimpaired and Impaired Older Adults.

Objective: Validation and widespread use of markers indicating decline in serial neuropsychological exams has remained elusive despite potential value in prognostic and treatment decision-making. This study aimed to operationalize neuropsychological decline, termed "neuropsychological (NP) decline," in older adults followed over 12 months in order to aid in the stratification of dementia risk along the cognitively unimpaired-to-mild cognitive impairment (MCI) spectrum. Methods: A prospective cohort study utilized 6,794 older adults from the National Alzheimer's Coordinating Center (NACC) database with a baseline diagnosis of normal cognition, impaired without MCI or with MCI. Operationalization of NP decline over 12-month follow-up used regression-based norms developed in a robustly normal reference sample. The extent to which each participant's 12-month follow-up score deviated from norm-referenced expectations was quantified and standardized to an NP decline z-score. Cox regression evaluated whether the NP decline metric predicted future dementia. Results: Participant's NP decline scores predicted future all-cause dementia in the total sample, χ2 = 110.71, hazard ratio (HR) = 1.989, p < 0.001, and in the subset diagnosed with normal cognition, χ2 = 40.84, HR = 2.006, p < 0.001, impaired without MCI diagnosis, χ2 = 14.89, HR = 2.465, p < 0.001, and impaired with MCI diagnosis, χ2 = 55.78, HR = 1.916, p < 0.001. Conclusion: Operationalizing NP decline over 12 months with a regression-based norming method allows for further stratification of dementia risk along the cognitively unimpaired-to-MCI spectrum. The use of NP decline as an adjunctive marker of risk beyond standard cognitive diagnostic practices may aid in prognosis and clinical decision-making.