ORIGINAL RESEARCH ARTICLE
Baseline Function and Rehabilitation Are as Important as
Stroke Severity as Long-term Predictors of Cognitive
Performance Post-stroke
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Sophia G. Girgenti, BS, Autumn O. Brunson, BS, and Elisabeth B. Marsh, MD
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Objective: Although individuals with low stroke severity tend to re-
cover well, cognitive impairment is common independent of stroke size
or location. In this study, the patterns of recovery for individual cogni-
tive domains and factors associated with outcome were examined.
Design: A prospectively enrolled cohort of patients with minor stroke
was administered cognitive testing at 1, 6, and 12 mos postinfarct. Com-
posite T scores were generated for global cognition and well as indepen-
dent cognitive domains at each time point. Paired t tests compared
changes in scores over time. Regression models identified factors asso-
ciated with improvement.
Results: A total of 46 patients, with an average NIH Stroke Scale
score of 2.7, were enrolled. Average age was 61.3 yrs. Patients im-
proved overall between 1 and 6 mos; however, distinct patterns of re-
covery were seen for different cognitive domains. The most significant
improvement was in spatial memory. Verbal memory scores remained
low longitudinally. Motor speed and executive function increased, then
plateaued. Despite a mean education of 13.6 yrs, only 36% of global
cognition scores were higher than or equal to the normative mean at
12 mos, and only 57% of patients improved their global scores from
6 to 12 mos. Late recovery was associated with lower NIH Stroke Scale
scores, higher 1-mo Montreal Cognitive Assessment scores, and reha-
bilitation. Baseline function predicted overall long-term recovery.
Conclusion: Patterns of recovery are distinct for individual cognitive do-
mains for patients with minor stroke. Stroke severity and rehabilitation
influence trajectory. Premorbid baseline predicts long-term outcome.
Key Words: Ischemic Stroke, Cognition, Rehabilitation, Recovery
(Am J Phys Med Rehabil 2023;102:S43–S50)
ne in four adults older than 25 yrs will experience a
O 1
stroke in their lifetime. Resulting symptoms can in-
clude motor, language, and cognitive deficits, leading to sig-
nificant morbidity.1,2 Fortunately, acute stroke treatment has
markedly improved owing to the use of intravenous tissue
From The Johns Hopkins School of Medicine Department of Neurology, Baltimore,
Maryland.
All correspondence should be addressed to: Elisabeth B. Marsh, MD, Department of
Neurology, The Johns Hopkins Hospital, 600 North Wolfe St, Phipps 446C,
Baltimore, MD 21287.
Funding: Dr Marsh’s work is supported in part by grants from the National Institutes
of Health (R21AG068802-01) and the American Heart Association
(18IPA34170313).
Sophia G. Girgenti and Autumn O. Brunson are in training.
Financial disclosure statements have been obtained, and no conflicts of interest have
been reported by the authors or by any individuals in control of the content of
this article.
Supplemental digital content is available for this article. Direct URL citations appear
in the printed text and are provided in the HTML and PDF versions of this article
on the journal’s Web site (www.ajpmr.com).
Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.
ISSN: 0894-9115
DOI: 10.1097/PHM.0000000000002125
American Journal of Physical Medicine & Rehabilitation • Volume 102, Number 2 (Suppl), February 2023
Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.
What Is Known
• Advances in acute treatment have altered the
landscape of stroke recovery. Post-stroke cognitive
dysfunction is common and leads to significant
disability; however, less is known regarding recov-
ery patterns of specific cognitive domains or their
expected evolution at early (1–6 mos) and later
(6–12 mos) time points.
What Is New
• It was found that each cognitive domain has a
unique trajectory that may significantly impact a
patient’s ability to return to work depending on
the nature of their job. In addition, along with
stroke severity, early cognitive performance and
rehabilitation are associated with 6–12-mo im-
provement, although premorbid baseline is most
predictive of overall cognitive outcome.
plasminogen activator and mechanical thrombectomy, which
convert large hemispheric lesions into smaller infarcts with
better long-term outcomes.3–5 Advancements in rehabilita-
tion techniques have also led to improved language and motor
outcomes. These advancements, leading to lower stroke se-
verity, have changed the landscape of stroke recovery.6 How-
ever, although patients can appear to have good functional
outcomes, cognitive impairment has become a prevalent
symptom, leading to long-term morbidity and disability.7,8
Patients with “minor stroke,” defined by low NIH Stroke
Scale (NIHSS) scores, often lack significant hemiparesis or
language deficits. However, despite low stroke severity, a lack
of cortical involvement, and small infarct volumes, many en-
dorse cognitive difficulties that, in the absence of other symp-
toms, prevent them from successfully returning to work and
their previous baseline level of function.9 Cognitive dysfunc-
tion can include difficulties with attention, memory, executive
function, multitasking, and cognitive fatigue.10 Unfortunately,
rehabilitation paradigms for cognitive recovery are less well
defined than those for language and motor deficits, and the pat-
tern of cognitive recovery with respect to specific cognitive do-
mains, particularly in the minor stroke population, has not been
well delineated. In addition, although many studies have eval-
uated the factors associated with improvement of hemiparesis
and aphasia, less is known about the most important predictors
of cognitive outcomes, particularly in those with minor stroke
and a lack of large cortical lesions. In general, factors such as
age, occupational status before the stroke6 (potentially an indi-
cator of baseline function), stroke subtype, and premorbid in-
dependence have been associated with improved longer-term
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 Girgenti et al.
outcomes, whereas premorbid disability and cognitive dys-
function have been shown to negatively impact stroke recovery
in the acute rehabilitation setting.11
Previous literature on stroke recovery has found that the
most significant improvement occurs predominantly in the
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first 30 days but may continue up to 12 mos post-stroke or even
longer.12 Clinically, it has been found that the greatest degree
of recovery in patients with minor stroke also occurs early
(1–6 mos post-infarct), whereas the cognitive trajectory
6–12 mos after stroke can be variable.8 In this study, the evolu-
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tion of specific cognitive patterns of dysfunction after minor
stroke over time, as well as the factors associated with contin-
ued recovery 6–12 mos postinfarct, was evaluated.
SUBJECTS AND METHODS
Study Population
Patients presenting to a large, urban Comprehensive
Stroke Center with their first-ever clinical ischemic stroke were
enrolled in a Stroke Recovery Study evaluating long-term out-
comes and cognitive recovery patterns.8 For this analysis, only
those with minor stroke who were seen in the clinic both at 1
and 12 mos postinfarct were included. “Minor stroke” was de-
fined by an admission NIHSS score of 10 or lower to capture
small deep lacunes that presented with motor deficits during
the acute period. All patients had NIHSS scores of 6 or lower
by their first follow-up clinic visit and had significantly im-
proved motor function, enabling the focus to be on persistent
cognitive deficits. Strokes were confirmed and infarct volumes
determined using diffusion weighted magnetic resonance im-
aging. Lesions were unilateral and supratentorial, without large
vessel involvement (M1 or M2). Patients had good premorbid
baseline function (modified Rankin Scale [mRS] score ≤2).
Individuals were excluded if they presented with an intracra-
nial hemorrhage, multifocal stroke involving multiple vascular
distributions, or evidence of aphasia or neglect on examina-
tion. Non–native English speakers were also excluded, as well
as those with a history of significant dementia, previous his-
tory of clinical stroke, neurologic disease, untreated hearing
loss, or psychiatric illness. Participants were enrolled when
they presented for their first follow-up after hospital discharge,
which occurred 6–8 wks post-stroke. Individuals were seen
again at 6 and 12 mos post-stroke and underwent repeat evalu-
ation. The study was approved by the Johns Hopkins Institu-
tional Review Board and all participants provided written in-
formed consent at the time of enrollment. Data are available
upon reasonable request and the manuscript was prepared in
accordance with STROBE reporting guidelines (Supplemen-
tary Checklist, Supplemental Digital Content 1, http://links.
lww.com/PHM/B871).
Clinical and Cognitive Assessment
At each visit, patients were administered the Stroke Im-
pact Scale, Patient Health Questionnaire (depression), Func-
tional Assessment of Chronic Illness Therapy (fatigue), and
Barthel Index for Activities of Daily Living (overall function)
to assess patient-reported outcomes. A battery of cognitive
tests, developed in conjunction with a neuropsychologist, eval-
uated verbal memory, spatial memory, motor speed, processing
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Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.
Volume 102, Number 2 (Suppl), February 2023
speed, and executive function. Tests included the Delis-Kaplan
Executive Function System (D-KEFS),13 Hopkins Verbal
Learning Test,14 Brief Visuospatial Memory Test–Revised,15
Symbol Digit Modalities Test,16 and Grooved Pegboard
Test.17 The Montreal Cognitive Assessment (MoCA)18 was
also included as a brief screen of global cognition. Additional
information, including social support (living with someone at
home), degree of rehabilitation (inpatient, outpatient, home, or
none), functional baseline (pre-stroke mRS score), medical co-
morbidities (history of smoking, hypertension, diabetes, and de-
pression), patient demographics (age, sex, self-identified race,
and education), and stroke characteristics (admission and dis-
charge NIHSS score, infarcted hemisphere, lesion volume,
and cortical vs. subcortical location), was collected.
Cognitive Analysis
For each test, T scores were generated from raw scores
based on age-specific normative data according to respective
test manuals. T-scores were averaged across tests to create
composite domain scores: spatial memory—Brief Visuospatial
Memory Test–Revised total learning and Brief Visuospatial
Memory Test–Revised delayed recall; verbal memory—Hop-
kins Verbal Learning Test total learning and Hopkins Verbal
Learning Test delayed recall; processing speed—Symbol Digit
Modalities Test written trial, Symbol Digit Modalities Test oral
trial, and D-KEFS Trail Making trial 1; motor processing
speed—D-KEFS Trail Making trial 5, Grooved Pegboard Test
dominant hand, and Grooved Pegboard Test nondominant
hand; and executive function—D-KEFS letter fluency, D-KEFS
category fluency, and D-KEFS Trails Making trials 2, 3, and 4.
A Global Composite Score was also created based on perfor-
mance on all tests including the MoCA. The highest score for
each patient in each domain was designated as their “Recovery
Score,” or peak score. Composite T scores for each domain
were compared at each time point to determine patterns of cog-
nitive recovery.
The MoCA was also evaluated independently as a screen
of global cognitive function at each time point. MoCA scores
<26 were defined as mild cognitive impairment,18 and scores
<19, as severe cognitive impairment.19
Statistical Analysis
Data were analyzed using Stata version 14 (College Sta-
tion, TX). Patterns of cognitive impairment and recovery were
determined for global cognition as well as independent cogni-
tive domains as detailed above. The degree of improvement in
global cognition and each cognitive domain was evaluated be-
tween 1 to 6 mos and 6 to 12 mos to determine differences in
improvement rates. Patients were then divided into those who
improved in global cognition (1) between 1 and 12 mos and
(2) between 6 and 12 mos vs. those who did not. Factors asso-
ciated with improvement at each time point were determined
using logistic regression analyses. Given the sample size,
the factors with a P value of ~0.1 were identified as trending
toward statistical significance and investigated further.
In a secondary analysis, the percentage of patients who
performed better than the normative mean (T ≥ 50) was calcu-
lated for each cognitive domain at each time point. A more
conservative analysis of patients whose scores were within 1
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 Volume 102, Number 2 (Suppl), February 2023 Predictors of Post-stroke Cognitive Impairment

in this analysis. Of those patients, 9 were missing 6-mo data

TABLE 1. Cohort characteristics
because of the COVID-19 pandemic limiting clinic visits.
Total Cohort (N = 46) Within the cohort, 21 (46%) were male and 14 (30%) were
Black. The average age at time of stroke was 61.3 yrs (SD,
Demographics 15.6 yrs), and the mean (SD) admission NIHSS score was
Age, mean (SD), years 61.3 (15.6)
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2.7 (2.3). Strokes were small, with a mean (SD) infarct volume
Sex, n (%) male 21 (45.7) of 6.9 (14.2) cc. Fifty-seven percent were exclusively subcorti-
Race, n (%) Black 14 (30.4) cal, whereas 9% were cortical only; 52% affected the left hemi-
Education, mean (SD), years 13.6 (2.7) sphere. A full description of the cohort can be found in Table 1.
Social support, n (%) yes 38 (84.4)
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Medical history, n (%)

Smoking 9 (19.6)
Global Cognitive Results
Hypertension 36 (78.3) The mean (SD) MoCA score at the 1-mo (first) clinical
Diabetes 17 (36.96) follow-up visit was 24.7 (3.6), with 46% of patients demon-
Depression 7 (15.2) strating some degree of cognitive impairment (MoCA <26)
Stroke characteristics and 7% demonstrating severe impairment (MoCA <19). At 6
Admission NIHSS, mean (SD) points 2.7 (2.3) mos, the mean (SD) increased to 25.8 (3.8), with only 38%
Discharge NIHSS, mean (SD) points 1.6 (1.8) of patients cognitively impaired (8% severe); however, by
Hemisphere, n (%) left 24 (52.2) 12 mos, it had decreased to 24.89 (with nearly 50% of individ-
Stroke volume, mean (SD), cc 6.9 (14.1) uals displaying some level of impairment). Standard deviations
Charlson Comorbidity Index, mean (SD) points 2.0 (1.5) increased over time, indicative of increased heterogeneity
Premorbid IQ, mean (SD) points 106.0 (11.6) within the cohort. A full description of cognitive performance
Prestroke mRS score, mean (SD) score 0.09 (0.28) can be found in Tables 2 and 3.
Isolated subcortical location, n (%) 26 (56.5)
Isolated cortical location, n (%) 4 (8.7) Patterns of Recovery
Although the overall trend for patients with minor stroke
standard deviation of the normative mean (T ≥ 40) was also was to improve substantially from 1 to 6 mos and display varying
performed. degrees of improvement from 6 to 12 mos, distinct patterns of re-
covery were found for each cognitive domain (see Fig. 1). Verbal
RESULTS memory T scores improved from 30.6 (SD, 9.0) at 1 mo to 33.6
Of the 133 patients with minor stroke enrolled in this lon- (SD, 8.8) at 6 mos and 35.1 (SD, 11.1) at 12 mos (Fig. 1) How-
gitudinal study, 46 had 12-mo data available and were included ever, although on the surface this seems stable, scores remained

TABLE 2. Clinical and behavioral outcomes

1 mo (n = 46) 6 mos (n = 37) 12 mos (n = 46)

Follow-up visit stroke characteristics
MoCA, mean (SD) points 24.7 (3.6) 25.8 (3.8) 24.9 (4.1)
<26, n (%) 21 (45.7) 14 (37.8) 22 (47.8)
<19, n (%) 3 (6.5) 3 (8.1) 4 (8.7)
BI, mean (SD) points 98.1 (5.9) 99.5 (3.3) 98.3 (9.5)
NIHSS, mean (SD) points 0.8 (1.2) 0.5 (1.4) 0.4 (0.9)
mRS, mean (SD) score 1.2 (1.0) 0.6 (0.8) 0.7 (1.0)
Patient-reported outcomes
FACIT, mean (SD) points 37.9 (12.1) 38.5 (10.8) 40.5 (9.1)
PHQ-9, mean (SD) points 4.8 (5.9) 3.4 (3.6) 2.9 (3.1)
Persistent symptoms, mean (SD) points on Likert scale 5.2 (1.7) 5.4 (1.8) 6.2 (1.1)
Quality of Life, mean (SD) points on Likert scale 4.9 (1.9) 5.5 (1.6) 6.1 (1.4)
Percentage recovered, mean (SD) points 72.2 (25.4) 80.7 (16.2) 88.9 (12.4)
Stroke Impact Scale, mean (SD)
1—upper limb 75.2 (28.8) 82.2 (20.4) 84.7 (20.1)
2—thinking 87.6 (17.9) 88.6 (11.4) 89.9 (11.9)
3—mood 85.4 (14.3) 86.7 (10.3) 87.2 (11.1)
4—communication 91.5 (18.0) 95.3 (7.1) 96.5 (8.5)
5—ADLs 89.5 (16.6) 98 (10.7) 95.6 (11.4)
6—mobility 87 (16.8) 92.5 (8.5) 91.0 (13.8)
7—fine motor 84.9 (22.1) 89.4 (15.3) 91.2 (14.0)
8—socialization 76 (22.6) 89.6 (13.2) 87 (20.0)
ADLs indicates activities of daily living; BI, Barthel Index; FACIT, Functional Assessment of Chronic Illness Therapy; PHQ-9, Patient Health Questionnaire-9.

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 Girgenti et al. Volume 102, Number 2 (Suppl), February 2023

score, the greatest percentage of individuals improved to

TABLE 3. Cognitive T scores
Cognitive Testing T Scores
Peg Board Task
Dominant hand
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“normal” spatial memory. Executive function demonstrated
1 mo 6 mos 12 mos an interesting pattern. Initially, 37% of patients scored ≥50,
and 74% were within 1 standard deviation of normal. These
numbers increased to 55% and 84.2%, respectively, at
29.1 (13.0) 47.4 (89.9) 35.5 (17.2)

6 mos but then fell to 49% and 83.7%, respectively, by

Nondominant hand
D-KEFS Letter Fluency Task
Letter fluency
D-KEFS Category Fluency Task
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28.5 (13.0) 31.8 (14.4) 36.2 (23.3) 12 mos. When considering global cognition, no patients
scored ≥50 at 1 mo, but this increased to greater than
49.7 (13.4) 52.6 (13.4) 56.5 (21.9) one-third at 6 mos and 50% by 12 mos, indicating a general-
ized long-term clinical improvement within this population

Category fluency 46.8 (14.4) 49 (15.2) 48.5 (14.8) overall. Full results can be seen in Figure 2.
D-KEFS Category Switching Task
Category switching 45.4 (12.7) 47.2 (12.8) 51.2 (14.7) Factors Associated With Improved Outcome
Switching accuracy 46.0 (11.3) 47.0 (12.5) 51.9 (12.7)
Whereas 94% of patients improved in global cognition be-
D-KEFS Trail Making Task
tween 1 and 12 mos, only 57% improved between 6 and
Trails 1 29.4 (13.9) 45.7 (15.1) 47.5 (12.6)
12 mos. Stroke severity (admission NIHSS score) and perfor-
Trails 2 44.1 (13.4) 49.3 (13.0) 46.8 (11.9)
mance on the MoCA at 1 mo trended toward importance for
Trails 3 44.1 (12.0) 48.1 (11.1) 46.6 (12.7)
continued recovery between 6 and 12 mos, along with rehabil-
Trails 4 50.2 (10.6) 51.1 (11.5) 51.4 (12.4)
itation, whereas premorbid baseline (prestroke mRS score) was
Trails 5 45.7 (11.9) 48.9 (11.9) 47 (10.3)
significantly associated with overall improvement from 1 to
Hopkins Verbal Learning Task
12 mos (Table 4).
Total recall 31.2 (9.1) 33.7 (9.1) 35.3 (11.0)
Delayed recall 29.9 (10.5) 33.5 (10.2) 35.3 (12.8)
Recognition 35.0 (12.4) 36.0 (11.5) 36.3 (13.0) DISCUSSION
Retention 34.6 (14.8) 38.4 (14.3) 41.1 (16.7) This study’s data suggest that cognitive impairment is
Brief Visuospatial Motor Task common after minor stroke and that overall clinical phenotypes
Total recall 43.2 (12.5) 46.9 (13.8) 47.8 (15.7) are similar across patients regardless of the location of their le-
Delayed recall 43.5 (14.0) 45.2 (15.2) 49.6 (14.9) sion. Furthermore, although global cognition largely improves
Recognition 13.7 (4.3) 13.9 (3.8) 14 (4.4) over time, the pattern of recovery for individual cognitive do-
Retention 12.8 (5.7) 12.4 (6.1) 15.1 (3.2) mains is distinct. This may be of significant prognostic impor-
Symbol Digit Modalities Task tance depending on a patient’s previous career or goals for re-
Written 43.0 (13.2) 48.1 (10.6) 49.6 (11.7) covery. As an example, verbal memory scores were quite low
Oral 37.8 (10.7) 42.2 (10.4) 44.1 (11.4) compared with those of control populations of similar age
Data are mean (SD). and did not recover well over time, whereas significant im-
provement was seen in the area of spatial memory after the first
6 mos. Motor speed and executive function tend to plateau af-
well below the normative mean of T = 50. Spatial memory im- ter 6 mos, whereas processing speed continues to improve.
proved substantially, increasing from a mean (SD) T score of These patterns are distinct from the traditional trajectories of
20.7 (8.0) at 1 mo to 46.4 (13.9) at 6 mos and 48.3 (15.1) at motor and language recovery.20,21 These patterns may impact
12 mos. Processing speed also improved from 1 to 6 mos and a businessman differently than an assembly line worker when
continued to improve between 6 and 12 mos, but to a lesser de- they consider if and when they may be ready to return to
gree. Motor speed improved significantly between 1 and the workforce.
6 mos, but subsequently plateaued, whereas improvement in ex- In addition to cross-sectional variability in performance,
ecutive function also appeared to plateau after 6 mos. Global cog- significant variation in recovery of cognitive impairment over
nition scores follow the same trend, the 1-mo mean being 36.6 time was found. Almost uniformly, there was at least some de-
and the 6- and 12-mo means plateauing to 44.5 (SD, 10.8 and gree of improvement in nearly all domains between 1 and
9.4, respectively). When comparing composite T scores for each 6 mos. However, the recovery between 6 and 12 mos was less
domain across time to the Recovery Score for that domain consistent, with wider standard deviations of mean scores and,
(Fig. 1), there is evidence of variation in patterns of recovery on patient-level analysis, a larger number of patients failing to
across domains over time as well as the increased variability at improve further, or even worsening. This was particularly true
12 mos, evidenced by increasing standard deviations. for verbal memory, which could have significant repercus-
When evaluating the percentage of patients scoring sions on one’s ability to function independently. Other studies
above the normative mean (T ≥ 50), similar patterns emerged have investigated cognitive recovery, including the impact of
(see Fig. 2). To account for mild impairment and uncertain specific cognitive domains.12,22 In a study by Jokinen et al.,23
premorbid baseline, a conservative approach was also taken they evaluated 409 patients with ischemic stroke at 3 and
and the percentage of patients scoring within 1 standard de- 15 mos post-stroke. They identified nine cognitive domains
viation of the normative mean (T ≥ 40) was determined. and found most patients to be impaired in multiple domains,
For verbal memory, the results remained low. Even at peak including memory, visuoconstructional skills, and executive
recovery, only 9% of patients reached T ≥ 50 and only 39% functions. They determined that domain-specific cognitive
scored T ≥ 40. Along with seeing the most improvement in impairment was associated higher mRS scores at 1.5 yrs

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 Volume 102, Number 2 (Suppl), February 2023 Predictors of Post-stroke Cognitive Impairment
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FIGURE 1. Recovery is distinct for independent cognitive domains over time. Average performance across subjects for each of the six cognitive
domains is depicted. The blue line represents the average group performance at each time point, whereas the orange line indicates the average peak
score over time for the group for each domain (the “Recovery Score”). Performance is well below the Recovery Score at 1 mo for all domains, most
likely indicating generalized impairment due to stroke, but improves variably for each domain over time.

post-stroke, regardless of stroke severity. However, many of
these patients had previous strokes (19%) and more severe
strokes (21% had an NIHSS score of 5–42). The study con-
cluded that higher stroke severity scores were associated with
multidomain cognitive deficits. The authors chose to evaluate
patients with strokes of milder severity to focus specifically on
cognitive deficits without the confounding effects of significant
hemiparesis, aphasia, or neglect on recovery and were able to
detect distinct patterns, of potentially high clinical significance.
Classically, stroke recovery occurs to the greatest extent
in the first 30 days after infarct, but improvement does continue
over the next 6–12 mos. This study did not focus on the acute
recovery time window of the first 30 days post-stroke, but in-
stead on the longer-term evolution of symptoms after initial re-
habilitation, in addition to factors associated with continued
improvement at the 6- and 12-mo time points. Some studies
have suggested that the slope of early (1–6 mos) improvement
is uniform for all patients and that stroke severity establishes
the lowest functional point.22 Others have also found that
NIHSS score predicts outcome.24 This would suggest that
factors such as age, premorbid function, and rehabilitation
may be less important. However, although a uniform im-
provement was also observed in nearly all patients between
1 and 6 mos, during later periods, the data from this study
suggest that other variables may also be important predictors
of continued improvement.

FIGURE 2. The percentage of patients scoring at or above the normative mean increases over time, but varies by cognitive domain. A T score of 40
corresponds to a raw score 1 standard deviation below the normative mean (T = 50). Scores below 40 are considered abnormal. Note the low
percentage of patients at 1 mo scoring higher than 40. It increases over time, indicating recovery, but remains low for many domains.

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 Girgenti et al. Volume 102, Number 2 (Suppl), February 2023

TABLE 4. Factors associated with global improvement over time

6- to 12-mo Recovery 1- to 12-mo Recovery

Odds Ratio P 95% Confidence Interval Odds Ratio P 95% Confidence Interval
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Age 0.977 0.304 0.934 1.020 0.954 0.245 0.882 1.033

Sex 0.857 0.833 0.205 3.580 2.500 0.448 0.235 26.600
Race 0.281 0.187 0.043 1.850 1.125 0.923 0.103 12.300
Comorbidities 1.070 0.788 0.658 1.740 0.649 0.174 0.348 1.210
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Education 0.930 0.593 0.715 1.211 1.040 0.862 0.702 1.530

Premorbid IQ 0.990 0.747 0.929 1.050 1.020 0.744 0.925 1.120
Prestroke mRS 0.706 0.812 0.040 12.400 0.065 0.027 0.006 0.730
Admission NIHSS 0.666 0.112 0.403 1.100 1.003 0.990 0.644 1.560
Discharge NIHSS 0.794 0.338 0.496 1.270 1.496 0.434 0.545 4.105
Stroke volume 1.050 0.394 0.941 1.170 1.004 0.941 0.907 1.110
Social support 0.271 0.271 0.026 2.780
Subcortical location 1.347 0.686 0.318 5.710
Cortical location 0.194 0.229 0.013 2.814
Stroke etiology 0.986 0.966 0.516 1.880 1.140 0.779 0.461 2.810
White matter disease burden 0.660 0.202 0.349 1.250 0.940 0.906 0.338 2.610
Hemisphere 0.982 0.981 0.227 4.250 0.452 0.511 0.042 4.820
Hypertension 1.050 0.955 0.191 5.760 1.240 0.862 0.111 13.800
Hyperlipidemia 1.156 0.856 0.241 5.530 2.000 0.516 0.248 16.200
Diabetes mellitus 0.583 0.471 0.135 2.530 0.167 0.139 0.015 1.790
Depression 1.067 0.937 0.214 5.330
Smoking 1.100 0.924 0.156 7.740
Rehabilitation 2.000 0.068 0.949 4.230 1.319 0.562 0.517 3.370
1-mo metrics
BI 1.110 0.417 0.865 1.417 1.080 0.306 0.930 1.260
NIHSS 0.754 0.453 0.360 1.570 1.270 0.701 0.372 4.350
mRS 0.920 0.827 0.442 1.919 1.040 0.950 0.323 3.330
FACIT 0.987 0.718 0.922 1.060 1.050 0.198 0.975 1.130
PHQ-9 1.020 0.823 0.852 1.220 0.924 0.275 0.802 1.060
MoCA 1.367 0.103 0.939 1.990 1.160 0.223 0.915 1.465
Likert scale–symptoms 0.756 0.318 0.436 1.310 1.070 0.822 0.586 1.962
Likert scale–QOL 0.745 0.273 0.439 1.262 1.170 0.590 0.668 2.034
Data in bold font are statistically significant values.
FACIT indicates Functional Assessment of Chronic Illness Therapy; PHQ-9, Patient Health Questionnaire-9; QOL, quality of life.

Importantly, stroke severity and NIHSS score seems to con-
tinue to influence improvement between 6 and 12 mos. It may be
that, in general, higher NIHSS scores represent larger infarcts
with increased disruption of cognitive networks that make reorga-
nization and recovery more difficult. Alternatively, as the NIHSS
overrepresents motor deficits compared with cognitive dysfunc-
tion, patients focus more on rehabilitating their physical symptoms,
when present, at the expense of other impairments. Avoiding this
potential confounding effect was attempted by excluding those with
significant hemiparesis, although mild weakness was still present in
a portion of individuals. However, given that performance on
the MoCA at 1 mo also trended toward significance, it is most
likely that both a low NIHSS score and a higher MoCA score
early on illustrate that the individual is on a favorable trajectory
that continues long-term. Similar results have been reported
with respect to motor recovery, where stroke severity is signif-
icantly associated with improvement of motor function and
early improvement on the Fugl Meyer Assessment can be used
to accurately demonstrate two distinct recovery patterns: pa-
tients showing rapid improvement who continue to improve
over time vs. patients improving only minimally and remaining
impaired long-term.25
Along with stroke severity and early cognitive performance,
rehabilitation was associated with continued improvement. It is
important to note that therapy was provided in the early stage
and was not standardized, but instead based on individual needs.
None of the cohort in this study qualified for inpatient rehabili-
tation after hospital discharge, so sessions were confined to the
outpatient setting. Some patients may have continued what they
were taught after sessions were stopped, or it may have placed
them on the favorable portion of the recovery curve. The timing,
duration, and content of the most effective therapeutic strategies
for motor and language recovery have been well described.26–28
The same rigor is required for cognitive rehabilitation tech-
niques. Existing cognitive therapies include antidementia drugs,
occupational therapy for cognitive retraining, and correction of
these impairments using computer programing.29–31 However,
little is known of the results of these management strategies. A
significant challenge is the heterogeneity of the deficits, which
necessitate individualizing therapy.

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Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.

 Volume 102, Number 2 (Suppl), February 2023
Although stroke severity, early cognitive performance, and
rehabilitation seem to be important for continued cognitive recov-
ery, the most important predictor of overall long-term outcome
was baseline function, as estimated by the premorbid mRS. Previ-
ous work has also suggested that individuals who were doing
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well, staying active, and engaging in activities leading up to their
infarct demonstrate better performance on objective tests of
post-stroke function as well as patient-reported outcomes.10 This
potentially provides evidence for the concept of cognitive reserve,
which explains why those with higher education and participation
WnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC1y0abggQZXdgGj2MwlZLeI= on 09/30/2023
in leisure activities have experienced less severe clinical cognitive
changes in the presence of different brain diseases, such as
age-related or Alzheimer disease pathology.32 This concept is dis-
tinct from that of compensation, which is the ability to maximize
performance in the event of brain damage using other regions or
structures not normally used for that function in healthy brain.33
As it is supposedly optimized in people who frequently engage
their brain, cognitive reserve is related to premorbid brain health.
Premorbid brain health is a major influencing factor in stroke re-
covery, and this relationship warrants further investigation.
This study is not without limitations. The relatively small
cohort of patients with minor stroke was recruited from a single
stroke center. A significant portion of those initially followed
failed to return for their 12-mo visit, in part because of the
COVID pandemic, and were thus excluded from this analysis.
On review, there were no major differences in the baseline
demographics or stroke characteristics of those returning vs.
those lost to follow-up, and cognitive performance at 1 mo
was similar for both groups, indicating that the sample was rep-
resentative; however, a larger sample would have likely yielded
more significant results rather than the trends observed. In ad-
dition, baseline cognitive function was unknown. To account
for this, T scores were used to allow for comparison with the
general population. Although it is possible that for some indi-
viduals a T score <50 was normal, for the entire cohort to have
such a poor baseline level would be unlikely. A more conserva-
tive analysis was also performed using a T score of 40 or higher
to account for potential baseline variability and similar results
were found. Finally, given the multiple administrations of cog-
nitive assessments, it is also possible that some degree of ob-
served improvement may have been due to practice effect.
However, alternative versions of tests were used for subsequent
evaluation when possible, and tests such as the MoCA have
demonstrated reliability even when administered as frequently
as every 3 mos.34 Furthermore, one of the striking findings of
the study was the lack of complete recovery over time in this
population for multiple cognitive domains, so if a practice ef-
fect is present, this finding is actually even more profound.
Despite these limitations, this study illustrates several im-
portant points regarding the cognitive recovery of patients with
minor stroke. First, cognitive impairment is common, even
with low NIHSS scores, with a similar clinical phenotype
across patients independent of lesion location. The greatest de-
gree of recovery is observed over the first 6 mos, although re-
covery within each cognitive domain is distinct. Factors includ-
ing stroke severity, 1-mo performance on screening tests like
the MoCA, and rehabilitation are associated with continued
improvement after 6 mos, although premorbid baseline is the
strongest predictor of long-term outcome. Future research is
needed to develop potential therapy options that may change
© 2023 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.
Predictors of Post-stroke Cognitive Impairment
the trajectory of recovery for those with cognitive dysfunction
after minor stroke.
ACKNOWLEDGMENTS
The staff at the Johns Hopkins Bayview Stroke Interven-
tion Clinic (BASIC); and Jason Brandt, PhD, and Keenan
Walker, PhD, for their expertise and assistance in creating
the brief cognitive assessment battery used in this study.
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