Previous findings suggest that time setting errors (TSEs) in the Clock Drawing Test (CDT) may be related mainly to impairments in semantic and executive function. Recent attempts to dissociate the classic stimulus-bound error (setting the time to “10 to 11” instead of “10 past 11”) from other TSEs, did not support hypotheses regarding this error being primarily executive in nature or different from other time setting errors in terms of neurocognitive correlates. This study aimed to further investigate the cognitive correlates of stimulus-bound errors and other TSEs, in order to trace possible underlying cognitive deficits.

We examined cognitive test performance of participants with preliminary diagnoses associated with mild cognitive impairment. Among 490 participants, we identified clocks with stimulus-bound errors (n = 78), other TSEs (n = 41), other errors not related to time settings (n = 176), or errorless clocks (n = 195).

No differences were found on any dependent measure between the stimulus-bound and the other TSErs groups. Group comparisons suggested TSEs in general, to be associated with lower performance on various cognitive measures, especially on semantic and working memory measures. Regression analysis further highlighted semantic and verbal working memory difficulties as being the most prominent deficits associated with these errors.

TSEs in the CDT may indicate underlying deficits in semantic function and working memory. In addition, results support previous findings related to the diagnostic value of TSEs in detecting cognitive impairment.

To describe the development and initial experience of a clinical research program in progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) in Canada: The Rossy PSP Centre, to share the data acquisition tools adopted, and to report preliminary results.

Extensive demographic and longitudinal clinical information is collected every 6 months using standardized forms. Biofluids are collected for biobanking and genetic analysis, and many patients are enrolled in neuroimaging research protocols. Brain donation is an important component of the program, and standardized processing protocols have been established, including very short death to autopsy times in patients undergoing medical assistance in dying.

Between Oct 2019 and Dec 2021, 132 patients were screened, 91 fulfilling criteria for PSP and 19 for CBS; age 71 years; 41% female; duration 5 years, age-of-onset 66 years. The most common symptoms at onset were postural instability and falls (45%), cognitive-behavioral changes (22%), and Parkinsonism (9%). The predominant clinical phenotype was Richardson syndrome (82%). Levodopa and amantadine resulted in partial and short-lasting benefit.

The Rossy PSP Centre has been established to advance clinical and basic research in PSP and related tauopathies. The extent of the clinical data collected permits deep phenotyping of patients and allows for future clinical and basic research. Preliminary results showed expected distribution of phenotypes, demographics, and response to symptomatic treatments in our cohort. Longitudinal data will provide insight into the early diagnosis and management of PSP. Future steps include enrollment of patients in earlier stages, development of biomarkers, and fast-tracking well-characterized patients into clinical trials.

Falls are a growing concern in seniors (≥65 yrs). Cognitive impairment (CI) and vestibular impairment (VI) increase fall risk. The aim of this study is to assess the prevalence of CI and VI in seniors experiencing falls.

Participants (≥65 yrs) with falls were recruited from Falls Prevention Programs (FPPs) and a Memory Clinic (MC). CI was assessed using the Montreal Cognitive Assessment at FPPs. VI was assessed at an MC and FFPs using the Head Impulse- (video + bedside), Headshake-, Dix-Hallpike test, and test of sensory interaction in balance. Questionnaires included Dizziness Handicap Inventory (DHI) and Activities-specific Balance Confidence Scale (ABC).

Of 41 participants (29 FPPs, 12 MC); mean age was 80.1 ± 7.1 years, and 58.5% were female. Overall, 82.9% had VI. At FPPs, 76.0% had CI, and 72.3% had CI + VI. Bilateral vestibular hypofunction (BVH) was more common than unilateral vestibular hypofunction (UVH) (70.6% vs. 29.4%); p = 0.016. Dizziness Handicap (DHI) was not different between those with a VI (23.5 ± 23.9) versus without VI [PVI + no impairment] (10.0 ± 15.4); p = 0.160. Balance confidence (ABC) was lowest in VI but not significantly different between those with a VI (63.4 ± 27.3) versus without VI [PVI + no impairment] (85.0 ± 16.5); p = 0.053.

VI and CI are prevalent in seniors experiencing falls. For seniors with history of falls, both cognitive and vestibular functions should be considered in the assessment and subsequent treatment. Screening enables earlier detection, targeted interventions, and prevention, reducing the clinical and financial impact.

Recent investigations now suggest that cerebrovascular reactivity (CVR) is impaired in Alzheimer’s disease (AD) and may underpin part of the disease’s neurovascular component. However, our understanding of the relationship between the magnitude of CVR, the speed of cerebrovascular response, and the progression of AD is still limited. This is especially true in patients with mild cognitive impairment (MCI), which is recognized as an intermediate stage between normal aging and dementia. The purpose of this study was to investigate AD and MCI patients by mapping repeatable and accurate measures of cerebrovascular function, namely the magnitude and speed of cerebrovascular response (τ) to a vasoactive stimulus in key predilection sites for vascular dysfunction in AD.

Thirty-three subjects (age range: 52–83 years, 20 males) were prospectively recruited. CVR and τ were assessed using blood oxygen level-dependent MRI during a standardized carbon dioxide stimulus. Temporal and parietal cortical regions of interest (ROIs) were generated from anatomical images using the FreeSurfer image analysis suite.

Of 33 subjects recruited, 3 individuals were excluded, leaving 30 subjects for analysis, consisting of 6 individuals with early AD, 11 individuals with MCI, and 13 older healthy controls (HCs). τ was found to be significantly higher in the AD group compared to the HC group in both the temporal (p = 0.03) and parietal cortex (p = 0.01) following a one-way ANCOVA correcting for age and microangiopathy scoring and a Bonferroni post-hoc correction.

The study findings suggest that AD is associated with a slowing of the cerebrovascular response in the temporal and parietal cortices.

Apolipoprotein E (APOE) E4 is the main genetic risk factor for Alzheimer’s disease (AD). Due to the consistent association, there is interest as to whether E4 influences the risk of other neurodegenerative diseases. Further, there is a constant search for other genetic biomarkers contributing to these phenotypes, such as microtubule-associated protein tau (MAPT) haplotypes. Here, participants from the Ontario Neurodegenerative Disease Research Initiative were genotyped to investigate whether the APOE E4 allele or MAPT H1 haplotype are associated with five neurodegenerative diseases: (1) AD and mild cognitive impairment (MCI), (2) amyotrophic lateral sclerosis, (3) frontotemporal dementia (FTD), (4) Parkinson’s disease, and (5) vascular cognitive impairment.

Genotypes were defined for their respective APOE allele and MAPT haplotype calls for each participant, and logistic regression analyses were performed to identify the associations with the presentations of neurodegenerative diseases.

Our work confirmed the association of the E4 allele with a dose-dependent increased presentation of AD, and an association between the E4 allele alone and MCI; however, the other four diseases were not associated with E4. Further, the APOE E2 allele was associated with decreased presentation of both AD and MCI. No associations were identified between MAPT haplotype and the neurodegenerative disease cohorts; but following subtyping of the FTD cohort, the H1 haplotype was significantly associated with progressive supranuclear palsy.

This is the first study to concurrently analyze the association of APOE isoforms and MAPT haplotypes with five neurodegenerative diseases using consistent enrollment criteria and broad phenotypic analysis.

Certain factors such as age and gender seem to affect the risk of developing post-concussion syndrome (PCS). We assessed the interactions between age, gender, concussion history and mechanism of injury in PCS patients so that a better understanding could guide the development of targeted prevention strategies.

Demographic data including age, gender, concussion mechanism of injury and concussion history were collected from (1) a prospective study evaluating PCS biomarkers and (2) a retrospective chart review of PCS patients. A total of 437 PCS patients who were assessed at the Canadian Concussion Centre or Toronto Western Hospital, Toronto, ON, were included.

Overall, there were more men with PCS; however, a greater percentage of women had PCS after a single concussion. The results showed that age, gender and concussion history are conditionally dependent on the mechanism of injury, and independent of one another. The relative frequency of having PCS was greater in the following instances: (1) being a woman and having had concussion from a fall or motor vehicle collision (MVC), (2) being older and having had concussion from a fall or MVC or (3) having a single concussion with cause being MVC or fall.

In patients with PCS, age and gender interact with the mechanism of injury to influence the risk of concussion. Targeted prevention strategies may be essential to prevent injuries leading to PCS.

Sporadic Jakob-Creutzfeldt disease (sCJD) and dementia with Lewy bodies (DLB) have overlapping clinical symptoms that can lead to their misdiagnosis. We delineated the clinical overlap between sCJD and DLB, and assessed the value of magnetic resonance imaging (MRI) to differentiate between them.

Medical records, MRI, electroencephalogram (EEG) and cerebrospinal fluid (CSF) were reviewed from 56 sCJD and 30 DLB subjects.

46% of sCJD subjects met probable DLB criteria and 40% of DLB subjects met probable CJD criteria. A greater proportion of sCJD subjects had cerebellar signs (66% vs. 10%, p<0.001), myoclonus (64% vs. 30%, p=0.002), and visual symptoms (other than hallucinations) (61% vs. 7%, p<0.001), whereas more DLB subjects had hallucinations (70% vs. 39%, p=0.007) and fluctuations (57% vs. 23%, p=0.002). Cortical and/or basal ganglia MRI diffusion weighted imaging hyperintensities consistent with sCJD were seen in 96% of sCJD subjects but in none with DLB. Logistic regression in sCJD revealed that those meeting probable DLB criteria were more likely to have occipital lobe involvement on MRI (OR 1.4, p=0.058, model p=0.022). Parietal lobe involvement on MRI was a predictor of “Other Focal Cortical signs” (OR 1.9, p=0.021). EEG and CSF assessments lacked sensitivity for sCJD as 48% of sCJD patients had a negative EEG; 67% of the 36 sCJD patents with a CSF evaluation had a negative or inconclusive 14-3-3 result. Too few DLB patients had EEG or CSF to assess their utility.

Sporadic CJD and DLB have significant symptom overlap. MRI helps differentiate these diseases and is related to the signs/symptoms observed in sCJD.