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Introduction Anxiety is a common symptom for those experiencing dementia and is associated with worse outcomes. The aim of the study was to examine which anxiety tools have been validated compared with a gold standard diagnostic criterion in persons with dementia. Methods We completed a systematic review of the literature, which was registered a priori with PROSPERO (CRD42016042123). Three databases were searched, MEDLINE, EMBASE, and PsycINFO, as well as the gray literature. Abstracts and full text were searched in duplicate for inclusion. Risk of bias was assessed in duplicate. Results We identified 9626 citations from all sources after duplicates were removed. Many excluded studies used tools for anxiety, for which no diagnostic accuracy study was identified. Four articles were included in the final synthesis. Included articles had between 32 to 101 participants with mild to moderate dementia. The gold standard criteria focused on either generalized anxiety or all anxiety subtypes. The prevalence of anxiety was between 27.7% and 63.4%. Three tools were examined, the Geriatric Anxiety Inventory, Penn State Worry Questionnaire, and the Rating Anxiety in Dementia (RAID) scale. Sensitivity varied but was the highest in the RAID at 90% and lowest in the self-rated version of the Geriatric Anxiety Inventory (58%). Discussion Given how burdensome the symptoms of anxiety are to persons with dementia, valid tools are needed to help identify symptoms. We identified three validated tools, but further validation of these and other tools are needed. Practitioners should consider the use of tools with high sensitivity such as the RAID in persons with dementia.

Background Cerebral amyloid angiopathy (CAA) causes cognitive decline, but it is not known whether it is associated with neuropsychiatric symptoms (NPS). Methods and Results Participants with CAA, mild cognitive impairment, mild dementia due to Alzheimer's disease, and normal cognition were recruited from stroke and dementia clinics and community advertising. NPS were captured using the Neuropsychiatric Inventory Questionnaire short form. The number and total severity (number multiplied by severity of each symptom [mild, moderate, or severe]) of NPS were analyzed using generalized linear regression with a negative binomial link and multiple linear regression, adjusting for age, sex, and education. A total of 109 participants (43 with CAA, 15 with Alzheimer's disease, 28 with mild cognitive impairment, and 23 with normal cognition) (mean age 71.1 [SD=7.6]; 53.2% male) were included. The most frequent NPS in CAA were depression/dysphoria (48.8%), irritability/lability (37.2%), agitation/aggression (37.2%), apathy/indifference (34.9%), and anxiety (32.6%). In adjusted models, patients with CAA had 3.2 times (95% CI, 1.7–6.0) more NPS symptoms and 3.1 units (95% CI, 1.0–5.1) higher expected severity score. The number of NPS was similar to patients with mild cognitive impairment (3.2 times higher than controls) but less than in patients with Alzheimer's disease dementia (4.1 times higher than controls). Within patients with CAA, there were 1.20 times (95% CI, 1.01–1.32) more NPS per 1% increase in white matter hyperintensity as a percentage of intracranial volume. Conclusions NPS are common in CAA, with a similar prevalence as in mild cognitive impairment. The association of the total number of NPS with higher white matter hyperintensity volume suggests that white matter damage may underlie some of these symptoms.

ObjectiveTo assess cerebrovascular reactivity in response to a visual task in participants with cerebral amyloid angiopathy (CAA), Alzheimer disease (AD), and mild cognitive impairment (MCI) using fMRI.MethodsThis prospective cohort study included 40 patients with CAA, 22 with AD, 27 with MCI, and 25 healthy controls. Each participant underwent a visual fMRI task using a contrast-reversing checkerboard stimulus. Visual evoked potentials (VEPs) were used to compare visual cortex neuronal activity in 83 participants. General linear models using least-squares means, adjusted for multiple comparisons with the Tukey test, were used to estimate mean blood oxygen level–dependent (BOLD) signal change during the task and VEP differences between groups.ResultsAfter adjustment for age and hypertension, estimated mean BOLD response amplitude was as follows: CAA 1.88% (95% confidence interval [CI] 1.60%–2.15%), AD 2.26% (1.91%–2.61%), MCI 2.15% (1.84%–2.46%), and control 2.65% (2.29%–3.00%). Only patients with CAA differed from controls (p = 0.01). In the subset with VEPs, group was not associated with prolonged latencies or lower amplitudes. Lower BOLD amplitude response was associated with higher white matter hyperintensity (WMH) volumes in CAA (for each 0.1% lower BOLD response amplitude, the WMH volume was 9.2% higher, 95% CI 6.0%–12.4%) but not other groups (p = 0.002 for interaction) when controlling for age and hypertension.ConclusionsMean visual BOLD response amplitude was lowest in participants with CAA compared to controls, without differences in VEP latencies and amplitudes. This suggests that the impaired visual BOLD response is due to reduced vascular reactivity in CAA. In contrast to participants with CAA, the visual BOLD response amplitude did not differ between those with AD or MCI and controls.

Systematic review data demonstrate that 5% of ALS cases are familial (FALS). Causative superoxide dismutase-1 (SOD1) mutations are identified in 10-20% of FALS. Few reports of FALS epidemiology exist in Canada. We completed a retrospective review of all FALS cases within the province of Alberta between 2002 and 2011. Descriptive summaries of genotypes identified and calculation of prevalences were performed. We reviewed 946 clinic database records and 49 subjects with FALS were identified (5.2%). Clinic charts for 47/49 were available and reviewed. Causative SOD1 mutations were observed in 17/47 (36%). The SOD1 I113T mutation was identified in 11/47 unrelated patients and was associated with a less variable survival than previously reported. The period and point prevalences of FALS in Alberta are approximately 2.05 per 100,000 (95% CI 1.51-2.73) and 4.68 per 1,000,000 (95% CI 2.42-8.18), respectively. In conclusion, we report 47 cases of FALS in Alberta over the past decade. The proportion of SOD1-positive FALS cases is higher than reported elsewhere. The high proportion of I113T mutations is comparable to that previously observed in the adjacent province of British Columbia.

BACKGROUND AND PURPOSE: Frontotemporal lobar degeneration is responsible for the cognitive abnormalities seen in patients with ALS. We sought to evaluate the in vivo neurochemical changes associated with this pathology indicative of neuronal loss and gliosis. MATERIALS AND METHODS: Twenty-four patients with ALS (2 with ALS-FTD) and 15 healthy controls were studied. High-field proton MR spectroscopy of the mesial prefrontal cortex was used to determine concentrations of NAA and mIns, markers of neuronal integrity and gliosis, respectively. Metabolite concentrations were correlated with cognitive tests (verbal fluency, ACE). RESULTS: NAA/mIns was decreased 17% ( P = .002). Abnormalities were present to a lesser degree in the individual metabolites NAA (decreased 9%; P = .08) and mIns (increased 11%; P = .06) than the ratio of the 2 metabolites. These measures did not correlate significantly with verbal fluency or the ACE. CONCLUSIONS: Prefrontal lobe degeneration exists in patients with ALS as indicated by an abnormal mesial prefrontal cortex neurochemical profile. Further study is necessary to determine the potential utility of the NAA/mIns ratio as a biomarker for frontal lobe degeneration in ALS.

Objectives Cognitive impairment occurs in up to 50% of patients with amyotrophic lateral sclerosis (ALS). Simple tools are required to identify such individuals, as cognitive impairment adversely impacts quality of life and survival. Our objective was to determine the potential utility of the Frontal Assessment Battery (FAB) and the Montreal Cognitive Assessment (MoCA) in evaluating frontal lobe and general cognitive impairment, respectively. We also assessed the feasibility of screening for cognitive impairment in those patients with advanced physical disability by modifying selected FAB and MoCA subtasks. Methods Fifty-four consecutive ALS patients were screened; 44 completed the FAB and 39 completed the MoCA. We administered modified tasks to patients with severe hand weakness or dysarthria. The patients were classified as cognitively impaired on each measure based on published cut-off scores of 14.11 on the FAB and 26 on the MoCA. Results Twenty-one percent and 53% of patients were impaired on the FAB and the MoCA, respectively. Scores from patients receiving modified instructions did not differ from those completing standard versions. There were statistically significant correlations between the MoCA total scores and forced vital capacity (FVC) and ALSFRS-R scores. There was no correlation between these variables and the FAB. Conclusions Both the FAB and MoCA detected cognitive impairment in ALS patients. While the MoCA classified more patients as cognitively impaired than the FAB, the latter was more feasible for assessing patients with physical impairment. Simple task modifications proved effective in allowing patients with speech and motor impairments to undergo screening. Future studies are required to validate both measures, establish optimal cut-off scores, and validate modifications.