BACKGROUND:In Parkinson's disease (PD) and dementia with Lewy bodies (DLB), the cholinergic system has been implicated in cognitive and gait decline. The nucleus basalis of Meynert (NBM), within the substantia innominata (SI), is the main cholinergic nucleus projecting to the cortex. In this study, the relationship between atrophy of the SI on cognitive phenotypes and quantitative gait performance was evaluated in relation to gray matter (GM) volume. METHODS:Ninety-nine participants - 20 control, 42 PD with normal cognition (PD-NC), 19 PD with mild cognitive impairment (PD-MCI) and 18 PD dementia or DLB patients (PDD/DLB) - were examined. Measures included Montreal Cognitive Assessment (MoCA) score, motor symptom severity, quantitative gait analysis measures and dual-task cost (DTC) to gait speed. Manual measurement of SI volume was performed on T1 MRI scans; automated methods were used for GM volumes. The relationships between gait changes, volumetric imaging and clinical measures were assessed. RESULTS:Smaller SI volumes were seen in PD-MCI and PDD/DLB subjects adjusting for age. SI and GM atrophy were both associated with greater step length variability, and GM was associated with increased DTC to gait speed. These were not significant after adjusting for the false discovery rate. Lower MoCA score was associated with impairments in gait speed, DTC to gait speed and gait variability. CONCLUSION:The SI was associated with cognitive impairment in participants with Lewy body diseases. However, more widespread cortical atrophy may be better related to selected cognitive aspects of gait (DTC to gait speed with animal fluency).

BACKGROUND AND OBJECTIVES:Cerebral amyloid angiopathy (CAA) is associated with intracerebral hemorrhage, cognitive decline, and dementia. We examined (1) associations between CAA, cognitive impairment, and depressive symptoms; (2) whether depressive symptoms mediate the relationship between CAA and cognition; and (3) whether CAA neuroimaging markers predict depressive symptom severity. METHODS:Recruitment occurred through memory and stroke prevention clinics across 2 sites. Cross-sectional data from probable CAA and controls were analyzed. Neuropsychological tests were grouped into episodic memory, executive function, and processing speed domains. Scores ≥5 on the Geriatric Depression Scale: Short Form (GDS-15) defined "possible depression." Regression and mediation analyses examined associations among CAA status, cognition, and depressive symptoms, and in CAA, associations between neuroimaging biomarkers and GDS-15. RESULTS:In 85 CAA (mean age 73.5; 35.3% female) and 83 controls (mean age 68.8; 62.7% female), CAA status was associated with poorer performance across cognitive domains. Higher GDS-15 scores were associated with poorer performance across domains. CAA participants had higher odds of "possible depression" (odds ratio 15.71; 95% CI 4.26-80.05, p < 0.001) and scored 2.71 times higher on the GDS-15 than controls (95% CI 2.10-3.51, p < 0.001). In mediation, "possible depression" accounted for significant proportions of the effect of CAA on episodic memory (11%; β = -0.14, 95% CI -0.30 to -0.03, p = 0.014) and executive function (9%; β = -0.14, 95% CI -0.30 to -0.02, p = 0.016), but not processing speed (2%; β = -0.04, 95% CI -0.18 to 0.08, p = 0.56). In 81 CAA participants, higher GDS-15 scores were associated with lower mean cortical thickness (count ratio [CR] 1.33 per SD decrease in thickness, 95% CI 1.09-1.62, p = 0.005), presence of cortical superficial siderosis (CR 2.04, 95% CI 1.35-3.09, p < 0.001), and higher CAA small vessel disease total score (CR 1.16, 95% CI 1.00-1.35, p = 0.047). DISCUSSION:CAA participants exhibited greater depressive symptoms and poorer cognition than controls. Depressive symptoms mediated a small portion of the association between CAA and cognition. Cerebral cortex damage may underlie some depressive symptoms. Interventions targeting CAA-related neurodegeneration and treatment of depressive symptoms may support cognitive health in CAA.

This study examined whether plasma Aβ 42/40, phosphorylated-tau ( p -tau), neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) may relate to cognitive function and other neuroimaging biomarkers in cerebral amyloid angiopathy. This is a cross-sectional analysis of a prospective cohort study of participants with CAA who had plasma collected, underwent magnetic resonance imaging (MRI) and cognitive evaluation. Plasma Aβ was quantified independently through Simoa and immunoprecipitation-mass spectrometry (IP-MS), while p -tau181, NfL and GFAP were quantified through Simoa. There were 45 participants with probable CAA (Boston criteria v2.0) eligible for analysis. In multivariable linear regression, adjusting for age, sex, and years of education, higher NfL levels were associated with lower Montreal Cognitive Assessment (MoCA) total score (β=-1.85, p  = 0.02) while lower Aβ 42/40 was associated with lower speed of processing both with IP-MS (β =0.63, p  = 0.003) and Simoa (β =0.38, p  = 0.02) methodology. After adjustment for age and sex, higher white matter hyperintensity (WMH) volume was associated with lower Aβ 42/40 (IP-MS), β =-0.48, p  = 0.009 and higher p -tau181, β =0.35, p  = 0.04, but not NfL or GFAP. Higher concentrations of plasma GFAP were associated with lower total cortical volumes (β =-0.40, p  = 0.042). Furthermore, higher levels of NfL were associated with lower global cerebrovascular reactivity (β=-0.46, p  = 0.008) and higher ordinal CAA severity scale score (aOR = 2.25, 95% CI: 1.17, 4.36, p  = 0.02). Lower plasma Aβ 42/40 was associated with lower speed of processing function, while plasma NfL was associated with worse performance on a global measure of cognitive performance, lower cerebrovascular reactivity, and higher CAA severity score. Interestingly, higher p -tau181 and lower Aβ 42/40 (IP-MS) was associated with higher WMH volumes. These findings suggest that cognitive impairment in patients with CAA may be associated with markers of progressive white matter damage rather than tau-related cortical injury.

INTRODUCTION:Cerebral amyloid angiopathy (CAA) is characterized by the deposition of beta-amyloid (Aβ) in small vessels leading to hemorrhagic stroke and dementia. This study examined whether plasma Aβ42/40, phosphorylated-tau (p-tau), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) differ in CAA and their potential to discriminate Boston Criteria 2.0 probable CAA from healthy controls. METHODS:Plasma Aβ42/40, p-tau-181, NfL, and GFAP were quantified using single molecule array (Simoa) and Aβ42/40 was also independently quantified using immunoprecipitation liquid chromatography mass-spectrometry (IPMS). RESULTS:Forty-five participants with CAA and 47 healthy controls had available plasma. Aβ42/40 ratios were significantly lower in CAA than healthy controls. While p-tau-181 and NfL were elevated in CAA, GFAP was similar. A combination of Aβ42/40 (Simoa), p-tau-181, and NfL resulted in an area under the curve of 0.90 (95% confidence interval: 0.80, 0.95). DISCUSSION:Plasma Aβ42/40, p-tau-181, and NfL differ in those with CAA and together can discriminate CAA from healthy controls. HIGHLIGHTS:Participants with CAA had reduced plasma Aβ42/40 ratios compared to controls. Plasma p-tau-181 and NfL concentrations are elevated in CAA compared to controls. Plasma GFAP was similar in CAA and controls. Together, plasma Aβ42/40, p-tau-181, and NfL had excellent discriminability for CAA.

Cerebral amyloid angiopathy (CAA) is characterized by deposition of amyloid-beta (Aβ) within the walls of the small blood vessels of the brain and leptomeninges. It causes ∼20% of intracerebral hemorrhage, increases the risk of dementia, and is common in patients with Alzheimer's disease (AD). Deposition of Aβ may result from impaired glymphatic clearance concurrent with a reduction in cerebrovascular reactivity, but this has not been investigated in patients with CAA or AD. Patients with CAA ( N  = 43) and AD ( N  = 16) patients and healthy controls (HC; N  = 53) underwent an MRI at 3T that included a T1-weighted and fluid attenuated inversion recovery (FLAIR) images, diffusion-weighted imaging (30 directions; b-value=1000s/mm 2 ) and BOLD imaging involving a 2-minute hypercapnic challenge (5% inspired CO 2 ). Glymphatic function was quantified by diffusion tensor imaging along the perivascular space (DTI-ALPS; ratio between diffusion in the perivascular space direction and diffusion of free water in the interstitium) while CVR was quantified as the % change in BOLD per mmHg increase in the end-tidal partial pressure of CO 2 . Group comparisons of DTI-ALPS were adjusted for age and sex while comparisons of CVR were adjusted for age, sex and hypertension. Associations between DTI-ALPS and CVR were adjusted for age, sex, hypertension, white matter hyperintensity volume and group. CAA and AD participants were predominantly male whereas HCs were predominantly female (Table). CAA participants were older with a greater prevalence of hypertension. DTI-ALPS was lower in patients with CAA and AD versus HCs (ANCOVA, p  <0.001; Figure 1A). Similarly, grey matter (GM), white matter (WM), and global CVR (mean of GM and WM) were lower in CAA and AD compared to HCs (all ANCOVAs, p  <0.001; Figure 1B). However, DTI-ALPS was not associated with GM (-0.18 (-0.73 - 0.36), p  = 0.504), WM (0.02, -0.84 - 0.89, p  = 0.646) or global CVR (-0.15, -0.85 - 0.55, p  = 0.94; Figure 2). Vascular contributions to reduced glymphatic function in CAA and AD may be more related to changes in vasomotion and pulsatility of blood flow through cerebral vessels than the ability of the cerebrovasculature to dilate.

BACKGROUND:This study examined whether plasma Aβ42/40, phosphorylated-tau (p-tau), neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) may relate to cognitive function and other neuroimaging biomarkers in cerebral amyloid angiopathy. METHOD:This is a cross-sectional analysis of a prospective cohort study of participants with CAA who had plasma collected, underwent magnetic resonance imaging (MRI) and cognitive evaluation. Plasma Aβ was quantified independently through Simoa and immunoprecipitation-mass spectrometry (IP-MS), while p-tau181, NfL and GFAP were quantified through Simoa. RESULT:There were 45 participants with probable CAA (Boston criteria v2.0) eligible for analysis. In multivariable linear regression, adjusting for age, sex, and years of education, higher NfL levels were associated with lower Montreal Cognitive Assessment (MoCA) total score (β=-1.85, p = 0.02) while lower Aβ42/40 was associated with lower speed of processing both with IP-MS (β =0.63, p = 0.003) and Simoa (β =0.38, p = 0.02) methodology. After adjustment for age and sex, higher white matter hyperintensity (WMH) volume was associated with lower Aβ42/40 (IP-MS), β =-0.48, p = 0.009 and higher p-tau181, β =0.35, p = 0.04, but not NfL or GFAP. Higher concentrations of plasma GFAP were associated with lower total cortical volumes (β =-0.40, p = 0.042). Furthermore, higher levels of NfL were associated with lower global cerebrovascular reactivity (β=-0.46, p = 0.008) and higher ordinal CAA severity scale score (aOR = 2.25, 95% CI: 1.17, 4.36, p = 0.02). CONCLUSION:Lower plasma Aβ42/40 was associated with lower speed of processing function, while plasma NfL was associated with worse performance on a global measure of cognitive performance, lower cerebrovascular reactivity, and higher CAA severity score. Interestingly, higher p-tau181 and lower Aβ42/40 (IP-MS) was associated with higher WMH volumes. These findings suggest that cognitive impairment in patients with CAA may be associated with markers of progressive white matter damage rather than tau-related cortical injury.

Mild Cognitive Impairment (MCI) may be caused by mixed pathologies. Blood markers indicative of Alzheimer pathology or neurodegeneration have not been extensively explored in patients with MCI who have features of Lewy Body disease (LB-MCI) (cognitive fluctuations, parkinsonism, hallucinations, and REM-sleep behavior disorder (RBD)). We compared plasma levels of amyloid beta (Aß), tau, glial-fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) between participants in COMPASS-ND who met criteria for LB-MCI with participant with MCI without these features, healthy controls (HC), and participants with Parkinson's disease (PD) with and without MCI. Participants with MCI, HC, and PD were recruited as part of the COMPASS-ND study and underwent assessment of demographic and clinical features. Participants with MCI were classified as LB-MCI based on one or more criteria for LB disease. Plasma biomarkers were determined for amyloid species (Aß 42/40 ratio), tau-181, GFAP, and (NfL using Simoa. Groups were compared using ANOVA with post hoc comparisons. Age and sex adjustment was done in ANCOVA models. Among participants with MCI in COMPASS-ND, there were 159 (97 M/62 F) with MCI but without LB features and 105 (46 M/32 F) with one or more of the LB-MCI criteria. There were 161 HC (54 M/107 F), 79 PD (42 M/37 F), and 41 PD-MCI (35 M/7 F). The Aß 42/40 ratio and tau-181 differed between groups, with the LB-MCI group showing a lower Aß 42/40 ratio and higher tau-181 than the other groups. Post hoc comparison indicated that the ratio was lower in LB-MCI than HC, PD, and PD-MCI while tau-181 was higher than HC, PD, and MCI without LB features. GFAP and NfL did not differ across groups. Age and sex adjustment did not alter the main findings. In COMPASS-ND, participants with features of LB-MCI showed a biomarker profile suggestive of high Alzheimer co-pathology. Higher tau-181 suggests that these individuals might have a higher pathological burden than the other groups. The influence of other co-pathologies (i.e., vascular) and the influence on outcomes will be examined in this cohort. Future studies should examine for the presence of synuclein pathology across these groups.

Cerebral amyloid angiopathy (CAA) is linked to cognitive decline and dementia. Depression is associated with worse cognition, and depressive symptoms are among the most frequently reported neuropsychiatric symptoms in CAA. This study examined the individual associations between CAA, cognitive impairment, and depressive symptoms. Cross-sectional data from a prospective cohort study of participants with CAA and controls were analyzed. Neuropsychological testing was converted to z -scores using test manual normative data for domains of episodic memory, executive function, and processing speed. The 15-item Geriatric Depression Scale: Short Form (GDS) was used to identify participants with symptoms suggestive of depression, with GDS scores >5 categorized as “possible depression”. Multivariable linear or logistic regression was used to determine whether CAA group status and cognitive domain z -scores were associated with possible depression, adjusting for age, sex, and education. Mediation analyses were used to determine the proportion of the effect of CAA on cognition that was mediated by possible depression, controlled for age, sex, and education. There were 85 CAA and 83 control participants. The median GDS was 1 (interquartile range 0-3) and 9.5% had possible depression (Table 1). Higher GDS score was associated with lower episodic memory, executive function and processing speed scores (Table 2). In multivariable logistic regression, CAA group status was associated with higher odds of having possible depression (OR 11.92, 95% CI 2.73 to 85.6, p  = 0.003). Compared with controls, the CAA group exhibited poorer episodic memory, executive function, and mean processing speed performance (Table 1). However, the effect of CAA on cognition was mostly not mediated by possible depression: episodic memory, 5% (95% CI 0 to 18%, p  = 0.06); executive function, 7% (95% CI 0 to 17%, p  = 0.06); and processing speed, 2% (95% CI -5% to 10%, p  = 0.58). Participants with CAA exhibited higher depressive symptoms and worse cognitive performance than controls. Patients with CAA should be screened and treated for depression. However, treating depression is unlikely to substantially improve cognitive function in CAA.

T1-weighted magnetization-prepared rapid gradient-echo (MPRAGE) is commonly included in brain studies for structural imaging using magnitude images; however, its phase images can provide an opportunity to assess microbleed burden using quantitative susceptibility mapping (QSM). This potential application for MPRAGE-based QSM was evaluated using in vivo and simulated measurements. Possible factors affecting image quality were also explored. Detection sensitivity was evaluated against standard multiecho gradient echo (MEGE) QSM using 3-T in vivo data of 15 subjects with a combined total of 108 confirmed microbleeds. The two methods were compared based on the microbleed size and susceptibility measurements. In addition, simulations explored the detection sensitivity of MPRAGE-QSM at different representative magnetic field strengths and echo times using microbleeds of different size, susceptibility, and location. Results showed that in vivo microbleeds appeared to be smaller (× 0.54) and of higher mean susceptibility (× 1.9) on MPRAGE-QSM than on MEGE-QSM, but total susceptibility estimates were in closer agreement (slope: 0.97, r 2 : 0.94), and detection sensitivity was comparable. In simulations, QSM at 1.5 T had a low contrast-to-noise ratio that obscured the detection of many microbleeds. Signal-to-noise ratio (SNR) levels at 3 T and above resulted in better contrast and increased detection. The detection rates for microbleeds of minimum one-voxel diameter and 0.4-ppm susceptibility were 0.55, 0.80, and 0.88 at SNR levels of 1.5, 3, and 7 T, respectively. Size and total susceptibility estimates were more consistent than mean susceptibility estimates, which showed size-dependent underestimation. MPRAGE-QSM provides an opportunity to detect and quantify the size and susceptibility of microbleeds of at least one-voxel diameter at B 0  of 3 T or higher with no additional time cost, when standard T 2 *-weighted images are not available or have inadequate spatial resolution. The total susceptibility measure is more robust against sequence variations and might allow combining data from different protocols.

BACKGROUND:Cerebral amyloid angiopathy (CAA) is associated with white matter damage and neurodegeneration. Gait is impaired in CAA; however, the neural basis of this impairment is unclear. RESEARCH QUESTION:Are gait impairments in patients with CAA associated with altered cerebral white matter diffusivity and/or atrophy of cortical and subcortical grey matter. METHODS:Participants with CAA (n=29), Alzheimer's disease (AD; n=16), and normal controls (n=47) were included. Gait was assessed using a 6 m walkway with parameters categorized into rhythm, pace, postural control, and variability domains. The dual-task cost (DTC) of gait speed was calculated for counting backwards, animal fluency, and serial sevens tasks. Whole-brain white matter disruption was quantified using the peak width of skeletonized mean diffusivity (PSMD), and thickness and volume of select cortical, subcortical, and cerebellar regions were quantified using FreeSurfer. RESULTS:In CAA participants, associations were found between PSMD and pace (standardized parameter estimate (β), 95 % confidence interval (CI): 0.17, 0.03-0.32), and medial orbital frontal cortical thickness and counting backwards DTC (parameter estimate (PE), 95 % CI: -5.7 %/SD, -0.24 to -11.23). Across all groups, including CAA, associations were found between PSMD and pace, variability, counting backwards DTC, and animal fluency DTC; between frontal cortical thickness and pace, counting backwards DTC, and animal fluency DTC; between cortical regions affected by AD (inferior parietal cortex, inferior and middle temporal gyrus) and counting backwards DTC; and between thalamus volume and postural control. SIGNIFICANCE:Reduced white matter structural integrity and grey matter loss is associated with poor overall gait performance in CAA, AD, and normal controls.

Background: Alzheimer’s disease (AD) and Lewy body disease (LBD) are characterized by early and gradual worsening perturbations in speeded cognitive responses. Objective: Using simple and choice reaction time tasks, we compared two indicators of cognitive speed within and across the AD and LBD spectra: mean rate (average reaction time across trials) and inconsistency (within person variability). Methods: The AD spectrum cohorts included subjective cognitive impairment (SCI, n = 28), mild cognitive impairment (MCI, n = 121), and AD (n = 45) participants. The LBD spectrum included Parkinson’s disease (PD, n = 32), mild cognitive impairment in PD (PD-MCI, n = 21), and LBD (n = 18) participants. A cognitively unimpaired (CU, n = 39) cohort served as common benchmark. We conducted multivariate analyses of variance and discrimination analyses. Results: Within the AD spectrum, the AD cohort was slower and more inconsistent than the CU, SCI, and MCI cohorts. The MCI cohort was slower than the CU cohort. Within the LBD spectrum, the LBD cohort was slower and more inconsistent than the CU, PD, and PD-MCI cohorts. The PD-MCI cohort was slower than the CU and PD cohorts. In cross-spectra (corresponding cohort) comparisons, the LBD cohort was slower and more inconsistent than the AD cohort. The PD-MCI cohort was slower than the MCI cohort. Discrimination analyses clarified the group difference patterns. Conclusions: For both speed tasks, mean rate and inconsistency demonstrated similar sensitivity to spectra-related comparisons. Both dementia cohorts were slower and more inconsistent than each of their respective non-dementia cohorts.

BackgroundPrevious reports have suggested that patients with cerebral amyloid angiopathy (CAA) may harbor smaller white matter, basal ganglia, and cerebellar volumes compared to age-matched healthy controls (HC) or patients with Alzheimer’s disease (AD). We investigated whether CAA is associated with subcortical atrophy.MethodsThe study was based on the multi-site Functional Assessment of Vascular Reactivity cohort and included 78 probable CAA (diagnosed according to the Boston criteria v2.0), 33 AD, and 70 HC. Cerebral and cerebellar volumes were extracted from brain 3D T1-weighted MRI using FreeSurfer (v6.0). Subcortical volumes, including total white matter, thalamus, basal ganglia, and cerebellum were reported as proportion (%) of estimated total intracranial volume. White matter integrity was quantified by the peak width of skeletonized mean diffusivity.ResultsParticipants in the CAA group were older (74.0 ± 7.0, female 44%) than the AD (69.7 ± 7.5, female 42%) and HC (68.8 ± 7.8, female 69%) groups. CAA participants had the highest white matter hyperintensity volume and worse white matter integrity of the three groups. After adjusting for age, sex, and study site, CAA participants had smaller putamen volumes (mean differences, −0.024% of intracranial volume; 95% confidence intervals, −0.041% to −0.006%; p = 0.005) than the HCs but not AD participants (−0.003%; −0.024 to 0.018%; p = 0.94). Other subcortical volumes including subcortical white matter, thalamus, caudate, globus pallidus, cerebellar cortex or cerebellar white matter were comparable between all three groups.ConclusionIn contrast to prior studies, we did not find substantial atrophy of subcortical volumes in CAA compared to AD or HCs, except for the putamen. Differences between studies may reflect heterogeneity in CAA presenting syndromes or severity.

BackgroundPersons with Parkinson's disease (PD) differentially progress to cognitive impairment and dementia. With a 3-year longitudinal sample of initially non-demented PD patients measured on multiple dementia risk factors, we demonstrate that machine learning classifier algorithms can be combined with explainable artificial intelligence methods to identify and interpret leading predictors that discriminate those who later converted to dementia from those who did not. MethodParticipants were 48 well-characterized PD patients (M-baseline age = 71.6; SD = 4.8; 44% female). We tested 38 multi-modal predictors from 10 domains (e.g., motor, cognitive) in a computationally competitive context to identify those that best discriminated two unobserved baseline groups, PD No Dementia (PDND), and PD Incipient Dementia (PDID). We used Random Forest (RF) classifier models for the discrimination goal and Tree SHapley Additive exPlanation (Tree SHAP) values for deep interpretation. ResultsAn excellent RF model discriminated baseline PDID from PDND (AUC = 0.84; normalized Matthews Correlation Coefficient = 0.76). Tree SHAP showed that ten leading predictors of PDID accounted for 62.5% of the model, as well as their relative importance, direction, and magnitude (risk threshold). These predictors represented the motor (e.g., poorer gait), cognitive (e.g., slower Trail A), molecular (up-regulated metabolite panel), demographic (age), imaging (ventricular volume), and lifestyle (activities of daily living) domains. ConclusionOur data-driven protocol integrated RF classifier models and Tree SHAP applications to selectively identify and interpret early dementia risk factors in a well-characterized sample of initially non-demented persons with PD. Results indicate that leading dementia predictors derive from multiple complementary risk domains.

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BackgroundParkinson’s disease (PD) and dementia with Lewy bodies (DLB) are part of a spectrum of Lewy body disorders, who exhibit a range of cognitive and gait impairments. Cognitive-motor interactions can be examined by performing a cognitive task while walking and quantified by a dual task cost (DTC). White matter hyperintensities (WMH) on magnetic resonance imaging have also been associated with both gait and cognition. Our goal was to examine the relationship between DTC and WMH in the Lewy body spectrum, hypothesizing DTC would be associated with increased WMH volume.MethodsSeventy-eight participants with PD, PD with mild cognitive impairment (PD-MCI), PD with dementia or DLB (PDD/DLB), and 20 cognitively unimpaired participants were examined in a multi-site study. Gait was measured on an electronic walkway during usual gait, counting backward, animal fluency, and subtracting sevens. WMH were quantified from magnetic resonance imaging using an automated pipeline and visual rating. A median split based on DTC was performed. Models included age as well as measures of global cognition and cardiovascular risk.ResultsCompared to cognitively unimpaired participants, usual gait speed was lower and DTC was higher in PD-MCI and PDD/DLB. Low DTC participants had higher usual gait speed. WMH burden was greater in high counting DTC participants. Frontal WMH burden remained significant after adjusting for age, cardiovascular risk and global cognition.ConclusionIncreased DTC was associated with higher frontal WMH burden in Lewy body disorders after adjusting for age, cardiovascular risk, and global cognition. Higher DTC was associated with age.

Background Parkinson’s disease (PD) increases risk for dementia and cascading adverse outcomes. The eight-item Montreal Parkinson Risk of Dementia Scale (MoPaRDS) is a rapid, in-office dementia screening tool. We examine predictive validity and other characteristics of the MoPaRDS in a geriatric PD cohort by testing a series of alternative versions and modelling risk score change trajectories. Methods Participants were 48 initially non-demented PD patients (Mage = 71.6 years, range = 65–84) from a three-year, three-wave prospective Canadian cohort study. A dementia diagnosis at Wave 3 was used to stratify two baseline groups: PD with Incipient Dementia (PDID) and PD with No Dementia (PDND). We aimed to predict dementia three years prior to diagnosis using baseline data for eight indicators that harmon-ized with the original report, plus education. Results Three MoPaRDS items (age, orthostatic hypotension, mild cognitive impairment [MCI]) discriminated the groups both independently and as a composite three-item scale (area under the curve [AUC] = 0.88). The eight-item MoPaRDS reliably discriminated PDID from PDND (AUC = 0.81). Education did not improve predictive validity (AUC = 0.77). Performance of the eight-item MoPaRDS varied across sex (AUCfemales = 0.91; AUCmales = 0.74), whereas the three-item configuration did not (AUCfemales = 0.88; AUCmales = 0.91). Risk scores of both configurations increased over time. Conclusions We report new data on the application of the MoPaRDS as a dementia prediction tool for a geriatric PD cohort. Results support the viability of the full MoPaRDS, and indicate that an empirically determined brief version is a promising complement.

IntroductionCerebral amyloid angiopathy (CAA) is a small vessel disease that causes covert and symptomatic brain hemorrhaging. We hypothesized that persons with CAA would have increased brain iron content detectable by quantitative susceptibility mapping (QSM) on magnetic resonance imaging (MRI), and that higher iron content would be associated with worse cognition.MethodsParticipants with CAA (n = 21), mild Alzheimer’s disease with dementia (AD-dementia; n = 14), and normal controls (NC; n = 83) underwent 3T MRI. Post-processing QSM techniques were applied to obtain susceptibility values for regions of the frontal and occipital lobe, thalamus, caudate, putamen, pallidum, and hippocampus. Linear regression was used to examine differences between groups, and associations with global cognition, controlling for multiple comparisons using the false discovery rate method.ResultsNo differences were found between regions of interest in CAA compared to NC. In AD, the calcarine sulcus had greater iron than NC (β = 0.99 [95% CI: 0.44, 1.53], q < 0.01). However, calcarine sulcus iron content was not associated with global cognition, measured by the Montreal Cognitive Assessment (p > 0.05 for all participants, NC, CAA, and AD).DiscussionAfter correcting for multiple comparisons, brain iron content, measured via QSM, was not elevated in CAA compared to NC in this exploratory study.

BACKGROUND:Within the spectrum of Lewy body disorders (LBD), both Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are characterized by gait and balance disturbances, which become more prominent under dual-task (DT) conditions. The brain substrates underlying DT gait variations, however, remain poorly understood in LBD.OBJECTIVE:To investigate the relationship between gray matter volume loss and DT gait variations in LBD.METHODS:Seventy-nine participants including cognitively unimpaired PD, PD with mild cognitive impairment, PD with dementia (PDD), or DLB and 20 cognitively unimpaired controls were examined across a multi-site study. PDD and DLB were grouped together for analyses. Differences in gait speed between single and DT conditions were quantified by dual task cost (DTC). Cortical, subcortical, ventricle, and cerebellum brain volumes were obtained using FreeSurfer. Linear regression models were used to examine the relationship between gray matter volumes and DTC.RESULTS:Smaller amygdala and total cortical volumes, and larger ventricle volumes were associated with a higher DTC across LBD and cognitively unimpaired controls. No statistically significant interaction between group and brain volumes were found. Adding cognitive and motor covariates or white matter hyperintensity volumes separately to the models did not affect brain volume and DTC associations.CONCLUSION:Gray matter volume loss is associated with worse DT gait performance compared to single task gait, across cognitively unimpaired controls through and the LBD spectrum. Impairment in DT gait performance may be driven by age-related cortical neurodegeneration.