Using a humanized APOE3/4 (Alzheimer’s disease genetic risk allele) mouse model we investigated the potential modulating effects of exercise on systemic risk factors and the ability of this mouse model to translate to active or sedentary, midlife, human participants. We present preliminary results of an ongoing, translational pilot study.

26 Midlife individuals, ages 40-65, were recruited from the community and dichotomized into active or sedentary groups following health screening and cognitive assessment. Blood samples were drawn from human participants for lipid assessment and other general health measures as well as peripheral growth factors concentrations (VEGF, BDNF and FGF21). Traditional, transgenic mouse models have helped the scientific community to understand biological mechanisms of Alzheimer’s disease (AD), but they do not develop significant neuronal loss, a hallmark of AD pathology. The MODEL-AD consortium has created a new “humanized” APOE4 model that has the human APOE4 allelic sequence in place of the mouse APOE gene; the model has shown known human phenotypes including deficits in cholesterol trafficking, amyloid clearance and BBB integrity. Of upmost importance, this model does not develop a full AD phenotype indicating that additional genetics and/or environmental factors are required as would be seen in human populations. We used males and females of this model to complete identical sedentary and active measures of each APOE genotype.

Lipid and general health marker assessment between mouse and human were similar and reproduced published literature. In both humans and mice we saw increased total cholesterol and HDL in active females and decreased total cholesterol and HDL in active males. We also saw similar relationships between APOE genotype, sex, and activity with regards to triglycerides. Although total cholesterol, HDL and LDL measures are the primary lipids needed to confirm or deny translation, other lipid measurements were not equivalent between the two models. Growth factor assessment in both species are also similar and reproduce published literature with regards to VEGF and BDNF as we see trending elevated levels in the active group. Less published on is the finding seen between active females and these elevated growth factors levels; our results indicates that although elevated as a result of exercise, this increase may be more prominent in females.

Based on the results found here we conclude that The Jackson Laboratory’s humanized APOE3/4 mouse model is a translatable model of vascular dysfunction, dementia and Alzheimer’s disease. We also conclude that exercise modulates these aspects by growth factor activation and increases resulting in downstream effects that reduce peripheral vascular risk factors and therefore reduce the risk of Alzheimer’s disease as a result of neuroinflammation. Complete, APOE genotype results from human participants are still ongoing. Descriptive analysis is limited by human samples size.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary form of cerebral small vessel disease leading to early cerebrovascular changes. These changes result from mutations in the NOTCH3 gene that cause progressive accumulations of granular osmiophilic material (GOM) deposits, thickening arterial walls and reducing or restricting blood flow in the brain. The clinical presentation of CADASIL is characterized by migraines with aura, early and recurrent strokes, progressive cognitive impairment, and psychiatric disturbances. CADASIL is rare but frequently underrecognized or misdiagnosed. A genetic condition with a 50% risk of inheritance from an affected parent, the gold standard for diagnosis is genetic testing to determine the presence of mutations in the NOTCH3 gene. This presentation aims to familiarize neuropsychologists with the condition of CADASIL through a unique case study highlighting important psychological, social, and ethical considerations raised by genetic testing.

This case study presents a 67-year-old, right-handed, married female diagnosed with CADASIL who was referred for neuropsychological evaluation of cognitive function and low mood concerns following multiple ischemic events.

Results revealed severe cognitive deficits in domains of attention, learning, and memory. Her superior verbal abilities and executive function remained largely intact. Assessment of mood revealed elevations in symptoms of depression and anxiety. The patient was aware of CADASIL in her father, paternal aunt, and younger brother, but elected to forego any genetic testing to confirm whether she had the condition until she experienced a stroke at age 61. She has two adult children who have also elected to forego testing and currently remain asymptomatic. Cognitive profile, mood disturbances, and patient perspectives on refraining from pre-symptomatic genetic testing for CADASIL diagnosis will be discussed.

Aspects of this case are consistent with a small body of literature evidencing distinct psychological, emotional, and social challenges among families carrying genetic risk of CADASIL. While providing an example of an often underrecognized neurological disorder with which neuropsychologists should be familiar, this case uniquely raises ethical questions relevant to care providers and current treatment guidelines regarding genetic testing among families carrying highly heritable neurological conditions. In particular, personal ethical challenges around deciding to pursue or forego pre-symptomatic testing, and implications for family planning, highlight the importance of genetic counseling for affected families.

A common assumption in clinical neuropsychology is that cerebrovascular risk is adversely associated with executive function, while Alzheimer’s disease (AD) primarily targets episodic memory. The goal of the present study was to determine the cross-sectional and longitudinal validity of these assumptions using validated markers of cerebrovascular and AD burden.

19271 longitudinally-followed participants from the National Alzheimer Coordinating Center (NACC) database (Mean age= 72.25; SD age= 10.42; 58% women; 51.6% CDR= 0, 33.7% CDR= 0.5, 14.7% CDR> 1) were included. Cognitive outcomes were a composite memory score and an executive function composite score (UDS3-EF; Staffaroni et al., 2020). Baseline presence of cerebrovascular disease was indexed by the presence of moderate to severe white matter hyperintensities or lacunar infarct on brain MRI (yes/no), while baseline AD pathology was indexed by the presence of a positive amyloid PET scan or elevated CSF AD biomarkers (yes/no). We used linear mixed effect models to assess the effects of baseline cerebrovascular disease, baseline AD pathology, and their interactions with time in study (years post baseline) controlling for baseline age, sex, education, and baseline MoCA score.

Baseline cerebrovascular disease was significantly associated with a lower intercept on executive functioning (between-person effect) (p < -0.001, 95% CI -0.37, -0.14) but not memory, while presence of AD biomarkers was associated with a lower memory intercept (p < -0.001, 95% CI -0.52, -0.39) but not executive function. However, only presence of AD pathology at baseline was associated with faster longitudinal decline on both memory and executive functioning over time. Baseline cerebrovascular disease did not independently relate to rate of cognitive decline.

Consistent with widely held assumptions, our between-person analyses showed that MRI evidence of cerebrovascular disease was associated with worse executive functioning but not memory, while biomarker evidence of AD pathology was associated with worse memory but not executive function. Longitudinally, however, AD is the primary driver of decline in both executive and memory function. These results extend our understanding of how pathology impacts cognition in aging cohorts and highlight the importance of using longitudinal models.

Cerebral amyloid angiopathy (CAA) is one of the most frequent causes of non-traumatic intracerebral hemorrhage (ICH). ICH recurrence risk is significantly higher in patients with CAA than for those without the condition, and CAA is a risk factor for the development of dementia, particularly Alzheimer’s disease. There is a growing body of research describing neuropsychological impairment observed in patients with CAA. Among patients with a history of CAA-related ICH, the most commonly identified cognitive impairments include attention, processing speed, executive functioning, and episodic memory. However, little is known about potential additive or synergistic effects of each CAA-related lesion (such as recurrent ICHs) on cognitive functioning.

We present a case of a 74-year-old female with sporadic CAA, who had recurrent ICHs involving the left occipitoparietal lobe, left frontoparietal lobe, right occipital lobe, and left frontal lobe. She experienced residual visual impairment and probable Charles Bonnet Syndrome. Her clinical presentation and cognitive functioning were tracked with an inpatient neuropsychological evaluation completed after each ICH occurrence within the past year, as well as an outpatient neuropsychological evaluation completed approximately 3-months post-discharge from her most recent hospital admission. Record review, including clinical notes, lab tests, and imaging results supplement her performance on serial inpatient and outpatient neuropsychological evaluations.

Data from three inpatient neuropsychological screenings and one lengthier outpatient evaluation are presented. With each inpatient evaluation, her profile demonstrated further cognitive decline involving visuospatial skills, semantic fluency, and episodic memory. In fact, results from her last inpatient screening raised concern for an underlying cortical degenerative process. In contrast, her follow-up outpatient evaluation, after three separate ICH events within one year, demonstrated an isolated set-shifting impairment, with intact performance across all other domains, which ruled out the prior suspicion of a cortical process.

While specific domains of cognition are more vulnerable in CAA, it is difficult to identify a specific and expected cognitive pattern given the extensive number of varied neurological insults patients typically develop throughout the disease course. This case demonstrates the wide range effects of repeated ICH, as well as the contrast between the acute effects of new lesions and the lasting effects of these lesions on cognitive ability after a period of recovery and stabilization. Given that our service was able to perform neuropsychological assessment in the acute phase of each ICH and in the subacute phase after a period of stabilization, this case adds to the literature by providing an example of the additive or synergistic effects of each CAA-related lesion over time.

brain white matter integrity as a result of vascular burden is associated with a form of late-life depression, known as vascular depression (VaDep). Black older adults may be particularly vulnerable to developing VaDep due to a higher prevalence of vascular conditions compared to White older adults. The current study examined whether clinical and imaging markers of vascular burden predicted depressive symptoms in an older Black sample. Based on the literature in primarily White samples, we expected greater clinical vascular burden and white matter hyperintensity (WMH) volume to predict greater depressive symptoms both cross-sectionally and over 4-year follow-up. We additionally hypothesized that participants with operationally-defined VaDep would have worse cognitive performance and slower gait speed compared to those without VaDep. Exploratory analyses examined race (Black vs. White) as an additional predictor.

This study used publicly available data from 113 Black older adults who were followed for four years in the Healthy Brain Project (a substudy of the Health, Aging, and Body Composition Study). Clinical vascular burden was defined as the number of vascular conditions (e.g., hypertension, diabetes, stroke); total WMH volume and WMH volume in the uncinate fasciculus, superior longitudinal fasciculus, and cingulum were considered imaging markers of vascular burden. Clinical and imaging-defined vascular burden were used to predict baseline depressive symptoms and average depressive symptoms over follow-up as measured by the Center for Epidemiologic Studies Depression Scale (CES-D). We then formed groups based on cutoffs for vascular burden (two or more conditions) and depressive symptoms (upper tertile of CES-D scores) to compare cognitive (Digit Symbol Substitution Test and 15-Item Executive Interview) and gait speed performance at baseline and changes over four years in VaDep, non-vascular depression, vascular only, and healthy groups. Exploratory analyses included 179 White older adults from the Healthy Brain Project dataset to examine race differences.

Total WMH volume and WMH volume in the uncinate fasciculus predicted higher depressive symptoms both cross-sectionally and longitudinally. However, no similar pattern emerged when using clinically-defined vascular burden as the predictor. The VaDep group had the slowest processing speed but the trajectory of decline over time did not differ between groups. The non-vascular depression group’s executive performance improved over time while performance by the other groups remained stable. Both VaDep and non-vascular depression groups’ gait speed declined over time. There was a stronger association between depression and uncinate fasciculus WMH in Black compared to White individuals, and the Black VaDep group had the slowest baseline processing speed of all groups.

This research supports the validity of the VaDep framework in Black older adults by showing the impact of WMH, particularly in the uncinate fasciculus, on depressive symptoms and identifying cognitive risks associated with VaDep in this population. Moreover, results suggest WMH may confer a greater risk for depression in Black compared to White older adults, and that VaDep disproportionately impacts processing speed in Black older adults. This work addresses an important gap in the VaDep literature by examining a group that has historically been underserved.

Previous research established that white matter hyperintensities (WMH), a biomarker of small vessel cerebrovascular disease, are strong predictors of cognitive function in older adults and associated with clinical presentation of Alzheimer’s disease (AD), particularly when distributed in posterior brain regions. Secondary prevention clinical trials, such as the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s (A4) study, target amyloid accumulation in asymptomatic amyloid positive individuals, but it is unclear the extent to which small vessel cerebrovascular disease accounts for performance on the primary cognitive outcomes in these trials. The purpose of this study was to examine the relationship between regional WMH volume and performance on the Preclinical Alzheimer Cognitive Composite (PACC) among participants screened for participation in the A4 trial. We also determined whether the association between WMH and cognition is moderated by amyloid positivity status.

We assessed demographic, amyloid PET status, cognitive screening, and raw MRI data for participants in the A4 trial and quantitated regional (by cerebral lobe) WMH volumes from T2-weighted FLAIR in amyloid positive and amyloid negative participants at screening. Cognition was assessed using PACC scores, a z-score sum of four cognitive tests: The Mini-Mental State Examination (MMSE), the Free and Cued Selective Reminding Test, Logical Memory Test, and Digit Symbol Substitution Test. We included 1329 amyloid positive and 329 amyloid negative individuals (981 women; mean age=71.79 years; mean education=16.58 years) at the time of the analysis. The sample included Latinx (n=50; 3%), non-Latinx (n=1590; 95.9%), or unspecified ethnicity (n=18; 1.1%) individuals who identified as American Indian/Alaskan Native (n=7; 0.4%), Asian (n=38; 2.3%), Black/African American (n=41; 2.5%), White (n=1551 ; 93.5%), or unspecified (n=21; 1.3%) race. We first examined the associations of total and regional WMH volume and amyloid positivity on PACC scores (the primary cognitive outcome measure for A4) using separate general linear models and then determined whether amyloid positivity status and regional WMH statistically interacted for those WMH regions that showed significant main effects.

Both increased WMH, in the frontal and parietal lobes particularly, and amyloid positivity were independently associated with poorer performance on the PACC, with similar magnitude. In subsequent models, WMH volume did not interact with amyloid positivity status on PACC scores.

Regionally distributed WMH are independently associated with cognitive functioning in typical participants enrolled in a secondary prevention clinical trial for AD. These effects are of similar magnitude to the effects of amyloid positivity on cognition, highlighting the extent to which small vessel cerebrovascular disease potentially drives AD-related cognitive profiles. Measures of small vessel cerebrovascular disease should be considered explicitly when evaluating outcomes in trials, both as potential effect modifiers and as possible targets for intervention or prevention. The findings from this study cannot be generalized widely, as the participants are not representative of the overall population.

Cardiovascular risk factors and white matter hyperintensities predict the progression and severity of cognitive symptoms in PD. While controversial, emerging evidence suggests that cerebrovascular dysfunction is an etiological driver of protein aggregation in neurodegenerative conditions, highlighting a need to understand how cerebrovascular function impacts cognitive function in PD. MRI cerebrovascular reactivity (CVR) paradigms provide an opportunity to measure the ability of the cerebral vessels to dilate or constrict in response to challenges. The current study evaluates whether whole brain CVR measures, degree of response (fit) and delay differ in PD with normal cognition (PD-NC) and PD with mild cognitive impairment (PD-MCI) relative to healthy controls (HC). Additionally, we evaluate if these metrics are associated with cognitive performance.

8 PD-NC, 11 PD-MCI and 11 age and sex-matched healthy controls (HC) participated in the study. PD participants were diagnosed with MCI based on the Movement Disorders Society Task force, Level II assessment (comprehensive assessment). Participants were asked to inhale gas enriched in CO2 to elicit a vasodilatory response while undergoing bold oxygen level-dependent magnetic resonance image (MRI). Whole brain fit to an end-tidal CO2 regressor and delay were used to quantify CVR in each participant. An analysis of covariance (ANCOVA) was used to evaluate group differences between HC, PD-NC, and PD-MCI in the whole brain fit and delay CVR measures accounting for age, sex, and education. Multiple regressions were conducted for each cognitive variable with whole brain fit and delay as the dependent variables adjusting for age, sex, and education.

A significant main effect of group was observed for whole brain CVR latency (F(2, 23) = 4.227; p = 0.027). Post hoc tests were not significant, though indicated a trend that PD-NC (18.14 ±1.94) and PD-MCI (18.15 ± 1.55) patients exhibited longer delays relative to HC (15.84 ± 2.37). Regression results indicated limited relationships between CVR measures and cognitive functioning.

PD patients (PD-NC and PD-MCI) exhibited longer CVR delays relative to HC, suggesting a delayed vasodilatory response in PD. Examination of the association between CVR metrics and cognition were not significant, though these results should be interpreted with caution given the small sample size.

White matter hyperintensities (WMH) are a radiological marker of small vessel cerebrovascular disease that are related to cognition and memory decline in aging and Alzheimer’s disease (AD). However, the mechanisms that link WMH to memory impairment and whether they interact with or act independently of AD pathophysiology are unclear. The transentorhinal cortex (BA35) is among the earliest anatomical regions to show tau deposition and subsequent atrophy, and baseline posterior WMH is related to longitudinal cortical thinning of the entorhinal cortex. However, it is unclear whether regional WMH are related to BA35 volume specifically, and whether this relationship is influenced by amyloid-β (Aβ) burden. We hypothesized that WMH in the vascular territory of the posterior cerebral artery (PCA), which perfuses both posterior and medial temporal lobe regions, would be associated with reduced BA35 volume and with lower memory in older adults independently of Aβ.

114 older adults without dementia, aged 60 to 98 years (mean (SD) = 78.31 (11.02), 71 (62.8%) women), were included. Regional WMH volumes were derived from T2-FLAIR images using ANTs, a vascular territory atlas and manual editing. Global Aβ was assessed with 18F-florbetapir PET, using SUVR of a cortical composite region (FBP mean SUVR) with a cerebellar reference region. Total transentorhinal (BA35) volume was derived using T1 and T2-weighted images using ASHS. To assess hippocampal pattern separation ability, an index of episodic memory, participants completed both object (MDT-O) and spatial (MDT-S) versions of a mnemonic discrimination task, with the lure discrimination index as the outcome. Using linear regressions, we first tested for associations among PCA-defined WMH, Aβ, BA35 volume, and MDT-S and MDT-O scores. We then tested whether the relationship between PCA-defined WMH and MDT-O performance was mediated by BA35 volume and whether this mediation was moderated by Aβ. All models adjusted for age, sex, and education.

PCA-defined WMH were related to higher FBP mean SUVR (b=0.287, p=0.042) and lower BA35 volume (b=-0.222, p=0.038). PCA-defined WMH were also negatively related to MDT-O performance (b=-0.229, p=0.044), but not to MDT-S (b=-0.171, p=0.118). FBP mean SUVR was not related to BA35 volume (b=-0.131, p=0.344) or MDT performance (MDT-S: b=-0.138, p=0.348; MDT-O: b=0.059, p=0.690). Furthermore, FBP mean SUVR did not interact with PCA-defined WMH to predict memory performance (interaction b=-0.039, p=0.973), nor BA35 volume (interaction b=-0.140, p=0.894). The association of PCA-defined WMH to MDT-O was fully mediated by BA35 volume (indirect effect b=-0.0005, 95% CI (-0.0014, -0.0003)). This mediation was not moderated by FBP mean SUVR (indirect effect b=-0.00001, 95% CI (-0.001, 0.001)).

We found that PCA-defined WMH were related to memory performance in older adults, and this association is fully mediated by transentorhinal volume. While PCA-defined WMH are related to higher global Aβ burden, there is no interaction between PCA-defined WMH and Aβ on BA35 volume. These findings point to an amyloid-independent vascular pathway towards memory decline in aging and AD. Future work should examine whether the pathway linking PCA-defined WMH to transentorhinal cortex atrophy and subsequent memory decline is mediated by regional tau pathology.

Blood pressure variability (BPV), independent of traditionally targeted average blood pressure levels, is an emerging vascular risk factor for stroke, cerebrovascular disease, and dementia, possibly through links with vascular-endothelial injury. Recent evidence suggests visit-to-visit (e.g., over months, years) BPV is associated with cerebrovascular disease severity, but less is known about relationships with short-term (e.g., < 24 hours) fluctuations in blood pressure. Additionally, it is unclear how BPV may be related to angiogenic growth factors that play a role in cerebral arterial health.

We investigated relationships between short-term BPV, white matter hyperintensities on MRI, and levels of plasma vascular endothelial growth factor (VEGF) in a sample of community-dwelling older adults (n = 57, ages 55-88) without history of dementia or stroke. Blood pressure was collected continuously during a 5-minute resting period. BPV was calculated as variability independent of mean, a commonly used index of BPV uncorrelated with average blood pressure levels. Participants underwent T2-FLAIR MRI to determine severity of white matter lesion burden. Severity of lesions was classified as Fazekas scores (0-3). Participants also underwent venipuncture to determine levels of plasma VEGF. Ordinal logistic regression examined the association between BPV and Fazekas scores. Multiple linear regression explored relationships between BPV and VEGF. Models controlled for age, sex, and average blood pressure.

Elevated BPV was related to greater white matter lesion burden (i.e., Fazekas score) (systolic: OR = 1.17 [95% CI 1.01, 1.37]; p = .04; diastolic: OR = 2.47 [95% CI 1.09, 5.90]; p = .03) and increased levels of plasma VEGF (systolic: ß = .39 [95% CI .11, .67]; adjusted R2 = .16; p = .007; diastolic: ß = .48 [95% CI .18, .78]; adjusted R2 = .18; p = .003).

Findings suggest short-term BPV may be related to cerebrovascular disease burden and angiogenic growth factors relevant to cerebral arterial health, independent of average blood pressure. Understanding the role of BPV in cerebrovascular disease and vascular-endothelial health may help elucidate the increased risk for stroke and dementia associated with elevated BPV.

Depression is a common problem among older adults and is further exacerbated by poor treatment response. The vascular depression hypothesis suggests that white matter hyperintensities (WMH) and executive dysfunction are main contributors to treatment non-response in older adults. While a previous meta-analysis has demonstrated the effects of executive dysfunction on treatment response, similar techniques have not been used to address the relationship between WMH and treatment response. Multiple commonly-cited studies demonstrate a relationship between WMH and treatment response, however, the literature on the predictive nature of the relationship is quite inconsistent. Additionally, many studies supporting this relationship are not randomized controlled studies. Critically examining data of well-controlled treatment response outcome studies using meta-analytic methods will allow for an aggregate evaluation of the relationship between WMH burden and treatment response.

A MEDLINE search was conducted to identify regimented antidepressant treatment trials contrasting white matter hyperintensity burden between remitters and non-remitters. Only regimented treatment trials for depressed outpatients aged 50 and older that had a pre-treatment measure of WMH burden and remitter/non-remitter comparison were included. Hedge’s g was calculated for each trial’s treatment effect. A Bayesian meta-analysis was used to estimate an aggregate effect size.

Eight studies met inclusion criteria. The log odds ratios average was significantly less than zero (.25, SE=.12, p=.019), suggesting that there is a significant effect of WMH hyperintensity burden on antidepressant remission status.

The purpose of this meta-analysis was to rigorously evaluate randomized controlled trials to determine the relationship between WMH burden and antidepressant treatment response. Findings revealed that WMH burden predicted antidepressant remission, that is, individuals with high WMH burden are less likely to meet remission criteria compared to individuals with low WMH burden. Results suggest that it may be important to consider vascular depression as a distinct treatment target of alternate interventions.

Older adults represent 50% of surgical patients and are disproportionately at risk of poor cognitive outcomes after surgery including delirium, accelerated cognitive decline, and dementia. Delirium alone is estimated to occur in up to 50% of older adults postoperatively, while research indicates it is preventable in 30-40% of cases. Individuals with pre-existing cognitive impairments or neurodegenerative diseases are at the highest risk of such outcomes, but (1) cognitive diagnoses are grossly underrepresented in patients' medical records, and (2) routine preoperative cognitive clearance remains rare. The purpose of this presentation is to demonstrate the extent and nature of cognitive vulnerability in older adults preparing for elective surgery within a tertiary care hospital. A case series is also reviewed to illustrate varying surgical outcomes with and without consideration of preoperative cognitive risk.

This presentation incorporated IRB-approved and data honest broker management to assess diagnoses and cognitive profiles of adults age 65 and older electing surgery with anesthesia between January 2018 and December 2019. Data were assessed across two phases of the Perioperative Cognitive Anesthesia Network (PeCAN) program within the University of Florida and UF Health. First, data from the preoperative anesthesia clinic were reviewed for the percentage of patients with cognitive difficulties within the patient problem list. Second, based on neuropsychological domains, the cognitive profiles of patients assessed by neuropsychologists within the preoperative anesthesia clinic were divided into primary attention, primary memory, or combined memory attention. From these patients, the presenter highlight cases to demonstrate how individuals with cognitive difficulties can be provided care by a multidisciplinary team to mitigate the presence of postoperative complications.

Of 14,794 older adults entering the tertiary care medical center for surgical procedures, 4% (n=591) of the sample had ICD cognitive or neurodegenerative codes in the record. When a comprehensive neurobehavioral assessments were conducted on 1,363 of these presurgical patients, 70% had confirmed cognitive deficits on neuropsychological testing. These deficits included primary attention and executive deficits (12%), primary memory impairment (27%), or both attention and memory impairment (31%). Cases from these patients are reviewed and highlight how preoperative cognitive risk status can inform conservative perioperative practices including opioid-sparing analgesia, depth of anesthesia monitoring, and postoperative inpatient geriatric medicine consultation.

Medical records listed cognitive diagnoses in 4% of hospital preoperative medical records, yet neuropsychological assessment of a subset of cases revealed a markedly higher rate of impairment. Patients with preoperative cognitive assessment show cognitive symptoms consistent with known neurological disorders of aging including Alzheimer's disease and cerebrovascular disease. Appreciation of pre-existing neurocognitive disorders can alter perioperative practices to prevent or reduce the risk of delirium and other postoperative neurocognitive changes. These data and cases reviewed will highlight how neuropsychology can be involved in perioperative care and champion perioperative interventions for perioperative "rescues".

The vascular depression hypothesis posits that there is a relationship between vascular disease and geriatric depressive symptoms. Black Americans are at higher risk for cardiovascular disease (CVD) than their White counterparts. However, it is not fully understood whether risk for CVD or potentially related neurovascular changes have a differential relationship in Black and White Americans. We investigated differences in the relationships between white matter hyperintensities, risk for CVD, and depressive symptoms in Black and White older adults.

Participants were derived from the National Alzheimer Coordinating Center database. Black (N = 120) and White (N = 120) participants were matched on age, sex, and education. White matter hyperintensity (WMH) and CVD burden data (sum of vascular conditions) on 320 individuals were analyzed (mean age = 75.9; 69.4% female). Age, sex, race, and education were included as covariates in separate regression models in which WMH and CVD burden predicted scores on the 15-item Geriatric Depression Scale (GDS-15). Follow-up stratified analyses were conducted to explore the relationship between WMH and CVD burden on GDS scores in the Black and White samples.

Lower WMH volume and higher CVD burden were associated with higher GDS scores in the total sample. Analyses stratified by race showed a positive effect of CVD burden on GDS scores only for the Black sample and a trend effect of WMH on GDS scores only for the White sample, with higher WMH volume associated with lower rather than higher GDS scores.

These findings are consistent with previous research showing that WMH and CVD burden are related to depression in older adults. Contrary to expectation, WMH had a negative trend association with GDS scores in the White sample. Findings also suggest that different etiologies may play a role in the clinical presentation of depression in Black and White Americans. Additional research is needed to further explore the relationships among CVD, its neural correlates, and depressive symptoms in diverse samples.

Decompressive craniectomy is part of the acute management of several neurosurgical illnesses, and is commonly followed by cranioplasty. Data are still scarce on the functional and cognitive outcomes following cranioplasty. We aim to evaluate these outcomes in patients who underwent cranioplasty following traumatic brain injury (TBI) or stroke.

In this prospective cohort, we assessed 1-month and 6-month neuropsychological and functional outcomes in TBI and stroke patients who underwent cranioplasty at a Brazilian tertiary center. The primary outcome was the change in the Digits Test at 1 and 6 months after cranioplasty. Repeated measures general linear models were employed to assess the patients' evolution and interactions with baseline characteristics. Effect size was estimated by the partial η2.

A total of 20 TBI and 14 stroke patients were included (mean age 42 ± 14 years; 52.9% male; average schooling 9.5 ± 3.8 years; 91.2% right-handed). We found significant improvements in the Digits Tests up to 6 months after cranioplasty (p = 0.004, partial η2 = 0.183), as well as in attention, episodic memory, verbal fluency, working memory, inhibitory control, visuoconstructive and visuospatial abilities (partial η2 0.106–0.305). We found no interaction between the cranioplasty effect and age, sex or schooling. Patients submitted to cranioplasty earlier (<1 year) after injury had better outcomes.

Cognitive and functional outcomes improved after cranioplasty following decompressive craniectomy for stroke or TBI. This effect was consistent regardless of age, sex, or education level and persisted after 6 months. Some degree of spontaneous improvement might have contributed to the results.

Acute coronary syndromes (ACS) are hard to diagnose because their clinical presentation is broad. Current guidelines suggest early clinical risk stratification to the optimal site of care. The aim of this study was to investigate the ability of Thrombolysis in Myocardial Infarction (TIMI); History, Electrocardiogram, Age, Risk Factors, Troponin (HEART); and Global Registry of Acute Coronary Events (GRACE) risk scores to predict the development of major adverse cardiac events (MACE) and the angiographic severity of coronary artery disease (CAD) in patients diagnosed with non-ST-segment elevation acute coronary syndrome (NSTEACS) in the emergency department (ED). In addition, independent variables associated with the development of MACE were also examined.

This study is a prospective, observational, single-center study. All patients over 18 years of age who were planned to be hospitalized for pre-diagnosed NSTEACS (NSTEMI + UAP) were included in the study consecutively. Patients’ demographic information and all variables necessary for calculating risk scores (TIMI, HEART, and GRACE) were recorded. Two experienced cardiologists evaluated all coronary angiograms and calculated the Gensini score.

The median age was 60 (IQR: 18) years, and 220 (61.6%) were male of the 357 patients included in the study. In this study, 91 MACE (52 percutaneous coronary interventions [PCI], 28 coronary artery bypass graft [CABG], three cerebrovascular disease [CVD], and eight deaths) occurred. The 30-day MACE rate was 25.5%. The low-risk group constituted 40.0%, 1.4%, and 68.0% of the population, respectively, in TIMI, HEART, and GRACE scores. Multiple logistic regression models for predicting MACE, age (P = .005), mean arterial pressure (MAP; P = .015), and High-Sensitive Troponin I (P = .004) were statistically significant.

The ability of the GRACE, HEART, and TIMI risk scores to predict severe CAD in patients with NSTEACS is similar. In patients with NSTEACS, the HEART and GRACE risk scores can better predict the development of MACE than the TIMI risk score. When low-risk groups are evaluated according to the three risk scores, the HEART score is more reliable to exclude the diagnosis of NSTEACS.

A large proportion of Alzheimer’s disease (AD) patients have coexisting subcortical vascular dementia (SVaD), a condition referred to as mixed dementia (MixD). Brain imaging features of MixD presumably include those of cerebrovascular disease and AD pathology, but are difficult to characterize due to their heterogeneity.

To perform an exploratory analysis of conventional and non-conventional structural magnetic resonance imaging (MRI) abnormalities in MixD and to compare them to those observed in AD and SVaD.

We conducted a cross-sectional, region-of-interest-based analysis of 1) hyperintense white-matter signal abnormalities (WMSA) on T2-FLAIR and hypointense WMSA on T1-weighted MRI; 2) diffusion tensor imaging; 3) quantitative susceptibility mapping; and 4) effective transverse relaxation rate (R2*) in N = 17 participants (AD:5, SVaD:5, MixD:7). General linear model was used to explore group differences in these brain imaging measures.

Model findings suggested imaging characteristics specific to our MixD group, including 1) higher burden of WMSAs on T1-weighted MRI (versus both AD and SVaD); 2) frontal lobar preponderance of WMSAs on both T2-FLAIR and T1-weighted MRI; 3) higher fractional anisotropy values within normal-appear white-matter tissues (versus SVaD, but not AD); and 4) lower R2* values within the T2-FLAIR WMSA areas (versus both AD and SVaD).

These findings suggest a preliminary picture of the location and type of brain imaging characteristics associated with MixD. Future imaging studies may employ region-specific hypotheses to distinguish MixD more rigorously from AD or SVaD.

Cerebrovascular disease is regarded as a potential cause of late-life depression. Yet, evidence for associations of neuroimaging markers of vascular brain disease with depressive symptoms is inconclusive. We examined the associations of neuroimaging markers and depressive symptoms in a large population-based study of middle-aged and elderly persons over time.

A total of 4943 participants (mean age = 64.6 ± 11.1 years, 55.7% women) from the Rotterdam Study were included. At baseline, total brain volume, gray matter volume, white matter volume, white matter hyperintensities volume, cortical infarcts, lacunar infarcts, microbleeds, white matter fractional anisotropy, and mean diffusivity (MD) were measured with a brain MRI (1.5T). Depressive symptoms were assessed twice with the Center for Epidemiologic Studies Depression scale (median follow-up time: 5.5 years, IQR = 0.9). To assess temporal associations of neuroimaging markers and depressive symptoms, linear mixed models were used.

A smaller total brain volume (β = −0.107, 95% CI −0.192 to −0.022), larger white matter hyperintensities volume (β = 0.047, 95% CI 0.010–0.084), presence of cortical infarcts (β = 0.194, 95% CI 0.047–0.341), and higher MD levels (β = 0.060, 95% CI 0.022–0.098) were cross-sectionally associated with more depressive symptoms. Longitudinal analyses showed that small total brain volume (β = −0.091, 95% CI −0.167 to −0.015) and presence of cortical infarcts (β = 0.168, 95% CI 0.022–0.314) were associated with increasing depressive symptoms over time. After stratification on age, effect sizes were more pronounced at older ages.

Neuroimaging markers of white matter microstructural damage were associated with depressive symptoms longitudinally in this study of middle-aged and elderly persons. These associations were more pronounced at older ages, providing evidence for the role of white matter structure in late-life depressive symptomatology.