Clinical value of Alzheimer's disease biomarker testing.

INTRODUCTION: In the Investigating the Impact of Alzheimer's Disease Diagnostics in British Columbia (IMPACT-AD BC) study, we aimed to understand how Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarker testing-used in medical care-impacted medical decision-making (medical utility), personal decision-making (personal utility), and health system economics. METHODS: The study was designed as an observational, longitudinal cohort study. A total of 149 patients were enrolled between February 2019 and July 2021. Patients referred to memory clinics were approached to participate if their dementia specialist ordered AD CSF biomarker testing as part of their routine medical care, and the clinical scenario met the appropriate use criteria for lumbar puncture and AD CSF biomarker testing. For the medical utility pillar, detailed clinical management plans were collected via physician questionnaires pre- and post-biomarker disclosure. RESULTS: Patients with completed management questionnaires (n = 142) had a median age of 64 (interquartile range: 59-69) years, 48% were female, and 60% had CSF biomarker profiles on the AD continuum. Clinical management changed in 89.4% of cases. AD biomarker testing was associated with decreased need for other diagnostic procedures, including brain imaging (-52.0%) and detailed neuropsychological assessments (-63.2%), increased referrals and counseling (57.0%), and guided AD-related drug prescriptions (+88.4% and -50.0% in biomarker-positive and -negative cases, respectively). DISCUSSION: AD biomarker testing was associated with significant and positive changes in clinical management, including decreased health care resource use, therapy optimization, and increased patient and family member counseling. While certain changes in management were linked to the AD biomarker profile (e.g., referral to clinical trials), the majority of changes were independent of baseline clinical presentation and level of cognitive impairment, demonstrating a broad value for AD biomarker testing in individuals meeting the appropriate use criteria for testing.

Vitamin D is associated with visual memory in young northern adolescents.

BACKGROUND: Vitamin D status has been linked to visual memory in adults. We hypothesized a similar association in young adolescents. METHODS: Participants were 9-13 years. The Rey-Osterrieth Complex Figure Task (ROCF), Rey Auditory Verbal Learning Task (RAVLT), Digit Span (Forward, Backward), and verbal fluency task assessed visual and verbal learning/memory, attention/working memory, and executive functioning/language, respectively. An at-home, mail-in blood spot test assessed 25(OH)D levels. RESULTS: Participants (N = 56) were 10.7 ± 1.3 years, 61% females, 25(OH)D levels 84.2 ± 25 nmol/L(39.9 - 167.2 nmol/L) and 41% had insufficient vitamin D status (<75 nmol/L). Only measures of visual memory (ROCF-Recall, -%Recall of Copy) were significantly correlated with 25(OH)D, r = .34, p < .01 and r = .33, p < .01, respectively, and 25(OH)D remained a significant independent predictor on multiple regression analyses, which included age and sex.(ROCF-Recall overall model: Adj R2 = .24, p < .001; for 25(OH)D: p = .009; ROCF-%Recall of Copy overall model: Adj R2 = .20 p < .002; for 25(OH)D: p = .01). Individuals with sufficient vitamin D performed significantly better only on these measures (t-tests; ROCF-Recall, p = .016, d = 0.68; ROCF-%Recall of Copy, p = .022, d = 0.64). Despite moderate effect sizes (d = 0.4-0.5) in the Younger Age Group (9-10 years), only in the Older Age Group (11-13 years) was 25(OH)D significantly correlated with ROCF-Recall, r = .64, p = .0001 and ROCF-%Recall of Copy, r = .64, p = .0001, as well as working memory (Digit Span-Backward), Spearman's r = .46, p = .013. Similarly, those in the Older Age Group with sufficient vitamin D performed significantly better on ROCF-Recall, p = .01, d = 1.07; and ROCF-%Recall of Copy, p = .009, d = 1.08. CONCLUSIONS: Vitamin D insufficiency was common in young adolescents. Similar to adults, visual memory was better among participants with higher 25(OH)D and those with sufficient levels. This effect was especially pronounced among older participants, suggesting possible time- and/or age-related implications of vitamin D status on cognition.

The dementia-inclusive choices in exercise project: Using participatory action research to improve physical activity supports for persons with dementia.

Persons with dementia have the right to equal inclusion in rehabilitation, including physical activity. However, the perspectives of persons with dementia are rarely integrated into decision-making related to physical activity programming, services, and supports. Here, we describe the participatory action research (PAR) approach used to develop the Dementia-Inclusive Choices for Exercise (DICE) toolkit, which aims to increase the quality and number of physical activity opportunities available to persons with dementia. The DICE Research Team included persons with dementia, a family care partner, exercise professionals, community and dementia service providers, health care professionals, and researchers who worked to: 1) Engage/maintain the Research Team; 2) Set/navigate ways of engagement; 3) Understand barriers to physical activity; 4) Prioritize the audience and actions; 5) Develop the toolkit; 6) Conduct usability testing; and 7) Implement and evaluate. Guided by the Behaviour Change Wheel, and informed by interviews, focus groups, and existing research, our PAR Team chose to prioritize training exercise providers; exercise providers can enable exercise for persons with dementia if they understand common changes with dementia and how to support persons with dementia in exercise. The content and format of the toolkit was co-developed: drafted by our Research Team, adapted through a stakeholder workshop, and refined through iterative development and usability testing. The product of our PAR process, the DICE toolkit, includes videos meant to destigmatize dementia, training modules and a training manual for exercise providers, a physical activity handout for persons with dementia, and wallet cards to help persons with dementia communicate their abilities, needs, and preferences. Our usability study indicated that the toolkit could be used by exercise providers and may improve attitudes about dementia. Our vision is that our co-developed DICE toolkit will empower exercise providers to improve physical activity opportunities and support for persons with dementia.

Quantitative Lipidomic Analysis of Serum Phospholipids Reveals Dissociable Markers of Alzheimer's Disease and Subcortical Cerebrovascular Disease.

BACKGROUND: Circulating phospholipid species have been shown to predict Alzheimer's disease (AD) prognosis but the link between phospholipid disturbances and subcortical small vessel cerebrovascular disease (CeVD) common in AD patients is not known. OBJECTIVE: Mass-spectrometry lipidomics was applied to quantify serum diacyl, alkenyl (ether), alkyl, and lyso phospholipid species in individuals with extensive CeVD (n = 29), AD with minimal CeVD (n = 16), and AD with extensive CeVD (n = 14), and compared them to age-matched controls (n = 27). Memory was assessed using the California Verbal Learning Test. 3.0T MRI was used to assess hippocampal volume, atrophy, and white matter hyperintensity (WMH) volumes as manifestations of CeVD. RESULTS: AD was associated with significantly higher concentrations of choline plasmalogen 18:0_18:1 and alkyl-phosphocholine 18:1. CeVD was associated with significantly lower lysophospholipids containing 16:0. Phospholipids containing arachidonic acid (AA) were associated with poorer memory in controls, whereas docosahexaenoic acid (DHA)-containing phospholipids were associated with better memory in individuals with AD+CeVD. In controls, DHA-containing phospholipids were associated with more atrophy, and phospholipids containing linoleic acid and AA were associated with less atrophy. Lysophospholipids containing 16:0, 18:0, and 18:1 were correlated with less atrophy in controls, and of these, alkyl-phosphocholine 18:1 was correlated with smaller WMH volumes. Conversely, 16:0_18:1 choline plasmalogen was correlated with greater WMH volumes in controls. CONCLUSION: This study demonstrates discernable differences in circulating phospholipids in individuals with AD and CeVD, as well as new associations between phospholipid species with memory and brain structure that were specific to contexts of commonly comorbid vascular and neurodegenerative pathologies.

Brain Imaging Abnormalities in Mixed Alzheimer's and Subcortical Vascular Dementia.

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

The role of biofactors in the prevention and treatment of age-related diseases.

The present demographic changes toward an aging society caused a rise in the number of senior citizens and the incidence and burden of age-related diseases (such as cardiovascular diseases [CVD], cancer, nonalcoholic fatty liver disease [NAFLD], diabetes mellitus, and dementia), of which nearly half is attributable to the population ≥60 years of age. Deficiencies in individual nutrients have been associated with increased risks for age-related diseases and high intakes and/or blood concentrations with risk reduction. Nutrition in general and the dietary intake of essential and nonessential biofactors is a major determinant of human health, the risk to develop age-related diseases, and ultimately of mortality in the older population. These biofactors can be a cost-effective strategy to prevent or, in some cases, even treat age-related diseases. Examples reviewed herein include omega-3 fatty acids and dietary fiber for the prevention of CVD, α-tocopherol (vitamin E) for the treatment of biopsy-proven nonalcoholic steatohepatitis, vitamin D for the prevention of neurodegenerative diseases, thiamine and α-lipoic acid for the treatment of diabetic neuropathy, and the role of folate in cancer epigenetics. This list of potentially helpful biofactors in the prevention and treatment of age-related diseases, however, is not exhaustive and many more examples exist. Furthermore, since there is currently no generally accepted definition of the term biofactors, we here propose a definition that, when adopted by scientists, will enable a harmonization and consistent use of the term in the scientific literature.

Soluble Epoxide Hydrolase-Derived Linoleic Acid Oxylipins in Serum Are Associated with Periventricular White Matter Hyperintensities and Vascular Cognitive Impairment.

White matter hyperintensities (WMH) are presumed to indicate subcortical ischemic vascular disease but their underlying pathobiology remains incompletely understood. The soluble epoxide hydrolase (sEH) enzyme converts anti-inflammatory and vasoactive cytochrome p450-derived polyunsaturated fatty acid epoxides into their less active corresponding diol species. Under the hypothesis that the activity of sEH might be associated with subcortical ischemic vascular disease and vascular cognitive impairment, this study aimed to compare the relative abundance of sEH substrates and products in peripheral blood between patients with extensive WMH (discovered due to transient ischemic attack; n = 29) and healthy elderly with minimal WMH (n = 25). The concentration of 12,13-DiHOME (a sEH-derived linoleic acid metabolite), and the ratio of 12,13-DiHOME to its sEH substrate, 12,13-EpOME, were elevated in the extensive WMH group (F1,53 = 5.9, p = 0.019), as was the 9,10-DiHOME/9,10-EpOME ratio (F1,53 = 5.4, p = 0.024). The 12,13-DiHOME/12,13-EpOME ratio was associated with poorer performance on a composite score derived from tests of psychomotor processing speed, attention, and executive function (ß = - 0.473, p = 0.001, adjusted r2 = 0.213), but not with a composite verbal memory score. In a mediation model, periventricular WMH (but not deep WMH), explained 37% of the effect of the 12,13-DiHOME/12,13-EpOME ratio on the speed/attention/executive function composite score (indirect effect = - 0.50, 95% bootstrap confidence interval [- 0.99, - 0.17] Z-score units). Serum oxylipin changes consistent with higher sEH activity were markers of vascular cognitive impairment, and this association was partly explained by injury to the periventricular subcortical white matter.

Peripheral lipid oxidative stress markers are related to vascular risk factors and subcortical small vessel disease.

Subcortical white matter hyperintensities (WMH), presumed to indicate small vessel ischemic vascular disease, are found commonly in elderly individuals with and without Alzheimer's disease (AD). Oxidative stress may instigate or accelerate the development of vascular disease, and oxidative stress markers are elevated in AD. Here, we assess independent relationships between three serum lipid peroxidation markers (lipid hydroperoxides [LPH], 8-isoprostane, and 4-hydroxynonenal) and the presence of extensive subcortical WMH and/or AD. Patients were recruited from memory and stroke prevention clinics into four groups: minimal WMH, extensive WMH, AD with minimal WMH, and AD with extensive WMH. Extensive WMH, but not AD, was associated with higher serum concentrations of 8-isoprostane and LPH. Peripheral LPH concentrations mediated the effect of hypertension on deep, but not periventricular, WMH volumes. 4-hydroxynonenal was associated with hyperlipidemia and cerebral microbleeds, but not with extensive WMH or AD. We conclude that lipid peroxidation mediates hypertensive injury to the deep subcortical white matter and that peripheral blood lipid peroxidation markers indicate subcortical small vessel disease regardless of an AD diagnosis.

Peripheral inflammatory markers indicate microstructural damage within periventricular white matter hyperintensities in Alzheimer's disease: A preliminary report.

INTRODUCTION: White matter hyperintensities (WMH) presumed to reflect cerebral small vessel disease and increased peripheral inflammatory markers are found commonly in Alzheimer's disease (AD), but their interrelationships remain unclear. METHODS: Inflammatory markers were assayed in 54 elderly participants (n = 16 with AD). Periventricular WMH were delineated from T1, T2/proton density, and fluid-attenuated magnetic resonance imaging using semiautomated fuzzy lesion extraction and coregistered with maps of fractional anisotropy (FA), a measure of microstructural integrity assessed using diffusion tensor imaging. RESULTS: Mean FA within periventricular WMH was associated with an inflammatory factor consisting of interleukin (IL)-1ß, tumor necrosis factor, IL-10, IL-21, and IL-23 in patients with AD (ρ = -0.703, P = .002) but not in healthy elderly (ρ = 0.217, P = .190). Inflammation was associated with greater FA in deep WMH in healthy elderly (ρ = 0.425, P = .008) but not in patients with AD (ρ = 0.174, P = .520). DISCUSSION: Peripheral inflammatory markers may be differentially related to microstructural characteristics within the white matter affected by cerebral small vessel disease in elders with and without AD.

Does high dose vitamin D supplementation enhance cognition?: A randomized trial in healthy adults.

BACKGROUND: Insufficiency of 25-hydroxyvitamin D [25(OH)D] has been associated with dementia and cognitive decline. However, the effects of vitamin D supplementation on cognition are unclear. It was hypothesized that high dose vitamin D3 supplementation would result in enhanced cognitive functioning, particularly among adults whose 25(OH)D levels were insufficient (<75nmol/L) at baseline. METHODS: Healthy adults (n=82) from northern British Columbia, Canada (54° north latitude) with baseline 25(OH)D levels ≤100nmol/L were randomized and blinded to High Dose (4000IU/d) versus Low Dose (400IU/d) vitamin D3 (cholecalciferol) for 18weeks. Baseline and follow-up serum 25(OH)D and cognitive performance were assessed and the latter consisted of: Symbol Digit Modalities Test, verbal (phonemic) fluency, digit span, and the CANTAB® computerized battery. RESULTS: There were no significant baseline differences between Low (n=40) and High (n=42) dose groups. Serum 25(OH)D increased significantly more in the High Dose (from 67.2±20 to 130.6±26nmol/L) than the Low Dose group (60.5±22 to 85.9±16nmol/L), p=0.0001. Performance improved in the High Dose group on nonverbal (visual) memory, as assessed by the Pattern Recognition Memory task (PRM), from 84.1±14.9 to 88.3±13.2, p=0.043 (d=0.3) and Paired Associates Learning Task, (PAL) number of stages completed, from 4.86±0.35 to 4.95±0.22, p=0.044 (d=0.5), but not in the Low Dose Group. Mixed effects modeling controlling for age, education, sex and baseline performance revealed that the degree of improvement was comparatively greater in the High Dose Group for these tasks, approaching significance: PRM, p=0.11 (d=0.4), PAL, p=0.058 (d=0.4). Among those who had insufficient 25(OH)D (<75nmol/L) at baseline, the High Dose group (n=23) improved significantly (p=0.005, d=0.7) and to a comparatively greater degree on the PRM (p=0.025, d=0.6). CONCLUSIONS: Nonverbal (visual) memory seems to benefit from higher doses of vitamin D supplementation, particularly among those who are insufficient (<75nmol/L) at baseline, while verbal memory and other cognitive domains do not. These findings are consistent with recent cross-sectional and longitudinal studies, which have demonstrated significant positive associations between 25(OH)D levels and nonverbal, but not verbal, memory. While our findings require confirmation, they suggest that higher 25(OH)D is particularly important for higher level cognitive functioning, specifically nonverbal (visual) memory, which also utilizes executive functioning processes.

CADASIL accelerated by acute hypotension: Arterial and venous contribution to leukoaraiosis.

OBJECTIVE: To underline the importance of blood pressure regulation in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and to describe changes that occur in the veins in this condition, specifically venous collagenosis associated with leukoaraiosis. METHODS: Case report with neuroimaging and pathologic data. RESULTS: A 61-year-old man with genetically confirmed CADASIL was initially lucid following a motor vehicle accident but subsequently became hypotensive (60/40 mm Hg) due to an open femur fracture and required intubation. Multiple new white matter infarcts appeared on brain imaging. A second hypotensive episode days later was associated with new coin-sized infarcts in the bilateral corona radiata and cerebellar peduncles, and resulted in quadriplegia. No embolic source was found on cardiac or vascular imaging. He died 5 weeks post trauma. Autopsy revealed extensive subcortical and periventricular leukoencephalopathy and multiple cavitations involving deep subcortical gray and white matter. Small arteries had thickened walls, disruption of the muscularis, and intimal periodic acid-Schiff (PAS)-positive material. Both larger periventricular and small caliber veins had thickened walls that were PAS-negative and trichrome-positive, consistent with venous collagenosis. There was no pathologic evidence of global hypoxia or diffuse axonal injury. CONCLUSIONS: The findings suggest rapid acceleration of CADASIL pathology from acute hypotension in the setting of impaired vasoreactivity. In addition, collagenosis of veins in the affected white matter regions suggests that the veins may play an important, though largely overlooked, role in maintaining white matter integrity.

Vitamin D and executive functioning: Are higher levels better?

OBJECTIVES: Insufficiency of 25-hydroxyvitamin D has been associated with cognitive impairment, particularly worse executive functioning. However, it remains unclear whether supratherapeutic levels (≥100 nmol L(-1)) are associated with even better performance than sufficient levels (defined as ≥50 nmol L(-1) or even ≥75 nmol L(-1)). The current investigation sought to examine this question. METHOD: Healthy adults (n = 142) were tested on four measures of executive functioning, including verbal fluency, digit span backward, CANTAB® Spatial Working Memory, and One Touch Stockings of Cambridge. A measure of attention (digit span forward) and memory (CANTAB® Verbal Recognition) were also assessed. Based on blood 25-hydroxyvitamin D [25(OH)D] levels, participants were divided into four groups: insufficient (<50 nmol L(-1)), low sufficient (50 to <75 nmol L(-1)), high sufficient (75 to <100 nmol L(-1)), and supratherapeutic (≥100 nmol L(-1)). Relationships between vitamin D status and cognition were assessed by analyses of covariance and hierarchical multiple regression, adjusted for age, education, sex, body mass index, mood, and physical activity level. Multivariate regression spline analyses were utilized to investigate nonlinearity. RESULTS: Performance on verbal fluency, but not other measures, differed by vitamin D status, analysis of covariance (ANCOVA), F(3, 127) = 2.70, p = .048; d = 0.50. Specifically, participants with supratherapeutic levels provided a greater number of words (M = 16.1, SE = 1.0) than those with insufficient (M = 12.0, SE = 1.0; p = .007, d = 0.78), low (M = 13.4, SE = 0.7; p = .026, d = 0.51), and high sufficient levels (M = 13.9, SE = 0.9; p = .080, d = 0.42). Similarly, vitamin D status was a significant independent predictor of verbal fluency (p = .025, d = 0.40). Spline analyses revealed that there is a positive, near-linear association between verbal fluency and 25(OH)D levels up to and exceeding 100 nmol L(-1). DISCUSSION: Supratherapeutic levels of vitamin D were associated with significantly better performance on verbal fluency. Importantly, commonly used cutoff levels and sufficiency categories have been based on bone health and optimal levels for cognition are unknown. These findings suggest that levels exceeding 100 nmol L(-1) may be optimal for at least some aspects of executive functioning.

The effects of Vitamin D Insufficiency and Seasonal Decrease on cognition.

BACKGROUND: Vitamin D3 (cholecalciferol) deficiency has been associated with dementia and cognitive decline. Which cognitive domains are most associated with D3 levels and how seasonal fluctuations in levels relate to cognition is unclear. We addressed these questions using a prospective observational study examining associations between D3 levels and cognition among individuals living in northern latitudes (54°N) in summer and winter. METHODS: Healthy adult participants underwent testing in summer and winter of D3 levels and cognition, using the Symbol digit Modalities test, phonemic fluency, digit Span and CANTAB battery. RESULTS: Of 32 participants tested in the summer, 46% were D3 insufficient (<75 nmol/L) and performed worse on digit Span Backward (DS-B) (µ=5.8, SD=2) than those who were sufficient (µ=7.9, SD=2), p=0.018. In multivariate analyses, sufficiency status was an independent predictor of dS-B, (b=0.41, p=0.02). The majority (63%) of 19 participants tested in winter were D3 insufficient, with levels declining by a median of 15 nmol/L overall. Those with insufficient levels performed worse (i.e., higher scores) on the CANTAB Spatial Working Memory (SWM) task (µ=36.1, SD=6 versus µ=29.3, SD=8), p=0.05). Those with larger drops in levels (≥15 nmol/L) showed decline/less improvement on the CANTAB one touch Stockings of Cambridge (OTS) task, (µ=0.50, SD=1.9 versus µ=-2.11, SD=2.6, p=0.01), a test of working memory/executive functioning. CONCLUSIONS: Vitamin D3 insufficiency and seasonal declines ≥15 nmol/L were associated with inferior working memory/executive functioning. While our findings require confirmation, they suggest that sufficient D3 levels should be maintained year-round, likely necessitating supplementation, at least during winter at higher latitudes.

Is encroachment of the carotid termination into the substantia innominata associated with its atrophy and cognition in Alzheimer's disease?

The internal carotid artery termination (CAT) ends in a T-shaped bifurcation just below the substantia innominata (SI), which contains cognitively strategic cholinergic neurons and undergoes atrophy in Alzheimer's disease (AD). This study investigated whether an elongated CAT with possible resulting encroachment into the SI would correlate with SI atrophy and with cognitive dysfunction in AD. We rated the degree of CAT encroachment upon the SI and measured SI volume on magnetic resonance imaging in 30 AD patients, 30 AD patients with subcortical small vessel disease, and 30 age-matched controls. CAT encroachment significantly correlated with SI volume after adjusting for age within the overall group and the groups with dementia. AD patients with higher CAT encroachment scores had lower SI volumes and lower attention, memory, and executive test scores. These data suggest that CAT encroachment may mechanically injure the SI, exacerbating cholinergic damage and contributing to cognitive impairment. This process may represent a possible previously underappreciated mechanism for interaction between large-vessel cerebrovascular disease and AD.

Long-term prediction of functional outcome after stroke using the Alberta Stroke Program Early Computed Tomography Score in the subacute stage.

Stroke patients who arrive at hospital more than 24 hours after symptom onset could benefit from a simple means of assessing long-term prognosis in this subacute stage. We evaluated whether clinical factors along with ischemic injury assessed subacutely using the Alberta Stroke Program Early Computed Tomography Score (ASPECTS) had predictive value for functional independence after stroke. Computed tomography (CT) scans obtained ≥ 2 days after first-ever ischemic stroke were scored independently and retrospectively by 3 stroke neurologists using the ASPECTS. Functional outcome was measured using the Functional Independence Measure, which assesses the amount of caregiver assistance required by patients during daily activities. Multiple linear regression was used to develop a predictive model for functional prognosis at 1 month, 3 months, and 1 year poststroke. For our 55 patients, CT scanning was done on average 4 days poststroke. The interrater agreement for subacute ASPECTS was excellent, with a κ-weighted value of 0.90. Lesions involving the frontal and superior parietal ASPECTS regions were significant predictors of lower Functional Independence Measure scores at all 3 time points studied. In combination with such factors as age, marital status, and the severity of initial neurologic deficit, a subacute ASPECTS score >5 had significant predictive value for greater functional independence at 3 months (R(2) = 0.701; P < .001) and 1 year (R(2) = 0.528; P < .001) poststroke. Our data indicate that in the subacute stage, ASPECTS is reliable and can help predict which patients may be likely to regain functional independence up to 1 year after sustaining ischemic stroke.