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(Stroke. 1995;26:735-742.)
© 1995 American Heart Association, Inc.
Articles |
Prospective CT Confirms Differences Between Vascular and Alzheimer's Dementia
From the Cerebrovascular Research Laboratories, Department of Veterans Affairs Medical Center, and the Department of Neurology, Baylor College of Medicine (J.S.M.), Houston, Tex.
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Abstract |
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 Top Abstract IntroductionSubjects and MethodsResultsDiscussionReferences |
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Background and Purpose Cognitive test performances were correlated prospectively with changes in cerebral CT measurements of atrophy, infarct volume, ventricular enlargement, local tissue density, and local perfusion to contrast annual rates of changes among patients with ischemic vascular dementia (IVD) or dementia of the Alzheimer type (DAT).
Methods The cerebral atrophic index (ATI; ratio of cerebrospinal fluid or infarcted brain to intracranial volume), infarct volume ratio, ventricular volume ratio (VVR; ventricular volume/intracranial volume), cortical and subcortical gray and white matter local perfusion (local cerebral blood flow [LCBF]), and local Hounsfield unit (HU) density were measured concurrently and compared longitudinally with Cognitive Capacity Screening Examinations (CCSE) scores among 24 treated IVD (age, 68.2±9.7 years; follow-up, 42±27 months) and 24 DAT patients (age, 74.2±6.2 years; follow-up, 30±19 months).
Results IVD annual changes were as follows: CCSE, +1.2±5.9; ATI, +2.1%/y; VVR, +3.2%/y; and LCBF in the subcortical basal ganglia, -0.74 mL · 100 g-1 · min-1 · y-1 (-1.8%/y). DAT annual changes were as follows: CCSE, -1.8 /y; ATI, +8.1%/y; VVR, +9.6%/y; cortical LCBF, -2.0 mL · 100 g-1 · min-1 · y-1 (-5.2%/y); LCBF in the basal ganglia, -3.0 mL · 100 g-1 · min-1 · y-1 (-6.7%/y); white matter LCBF, -0.75 mL · 100 g-1 · min-1 · y-1 (-4.1%/y); and all cortical tissue densities, -0.83 HU/y (-2.1%/y). In IVD, multiple regression analyses correlated cognitive changes directly with (1) recurrent silent infarctions and (2) bidirectional changes of perfusions within frontal white matter, thalamus, and internal capsules. In DAT, cognitive declines correlated with cerebral atrophy and cortical hypoperfusion related to frontotemporal and parietal cortical polioaraiosis (decreased gray matter tissue densities).
Conclusions In IVD, recurrent strokes were not observed clinically during risk factor control, and antiplatelet therapy and cognitive impairments improved or stabilized. In DAT, cognitive performance relentlessly declined. Ischemic pathogenesis for vascular dementia is supported by the following: (1) cognitive declines correlate directly with recurrent "silent" strokes, and (2) bidirectional cognitive changes correlate directly with frontal white matter, thalamic, and internal capsular perfusional changes.
Key Words: Alzheimer's disease • cerebral blood flow • dementia • tomography
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Introduction |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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In the United States, ischemic vascular dementia (IVD) is second to dementia of the Alzheimer type (DAT) as the most common cause of cognitive impairments among the elderly.1 2 3 4 However, the definition, prevalence, and very existence of IVD remain controversial.5
To document pathogenetic differences between IVD and DAT, concurrent, longitudinal measurements among demented patients with either IVD or DAT were determined to compare annual rates of change in neurological, psychometric, and CT manifestations.
Cognitive impairments in IVD have been correlated with (1) risk factors for stroke, (2) cerebral atrophy, (3) numbers and sites of cerebral infarctions, and (4) limited educational and occupational levels.6 7 8 9 10 11 Among DAT patients, cognitive impairments have been correlated with (1) ventricular enlargement12 13 14 15 16 17 and (2) bihemispheric declines in cortical blood flow and metabolism.18 19 20 21 22 Progressive declines in cortical perfusion in DAT were ascribed to decreased cortical metabolic demands resulting from Alzheimer's degenerative changes, which principally affect the cerebral cortex.18 19 20 21 22
Among IVD patients, prospective studies designed to correlate cognitive test performances with changes in local cerebral perfusion, recurrent strokes, and cerebral atrophy have been extremely rare,23 and longitudinal comparisons of cognitive test scores with cerebral atrophy, infarct volumes, changes in cortical density, and local perfusion compared between DAT and IVD patients are not available.
For these reasons the present prospective and concurrent study was designed to compare annual rates of change in neurological, psychometric, and cerebral CT measurements between groups of patients with probable IVD or DAT to correlate annual changes in cognitive test performance with annual changes in (1) ventricular volume, (2) atrophic index, (3) cerebral infarct volume, (4) volume of normal and abnormal cortical and subcortical gray and white matter, (5) local tissue density, and (6) local tissue perfusion.
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Subjects and Methods |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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As displayed in Table 1
, 24 patients with
probable IVD due to multiple small strokes (mean age, 68.2±9.7 years)
were compared during follow-up with 24 probable DAT patients (mean age,
74.2±6.2 years) by the use of identical concurrent longitudinal
designs. Patients were admitted sequentially after referral by local
physicians, the Alzheimer's Disease and Related Disorders
Association, and Stroke Groups of Houston.
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Informed consents were signed according to protocols approved by the Institutional Review Board of Baylor College of Medicine. Participants returned for serial testing as outpatients at 6- to 12-month intervals. Mean follow-up intervals were 42.3±27.2 months (range, 6 to 89 months) for IVD patients and 30.1±18.7 months (range, 10 to 75 months) for DAT patients. At each visit, patients underwent medical, neurological, and neuropsychological examinations by the authors. Neuropsychological test batteries performed included the Cognitive Capacity Screening Examinations (CCSE),24 25 26 Hamilton Depression Rating Scale,27 Wechsler Adult Intelligence Scale (Revised), Mini-Mental State Examination,28 Diagnostic and Statistical Manual of Mental Disorders, edition 3, revised (DSM-III-R) dementia rating scales,29 and standard tests of memory, motor performance, and language.
At entry, dementia met DSM-III-R criteria.29 Both groups had CCSE scores that fell below the cutoff score of 25, which is known to indicate cognitive impairments. Among high school graduates, CCSE test scores <25 also correlate with impairments demonstrated by standard neuropsychological and neurobehavioral testing.24 25 26 CCSE scoring is reliable and reproducible (±1) for quantitating cognitive changes among elderly patients with IVD and DAT. In the present series of patients, more extensive test battery scores were determined and correlated well with CCSE testing. CCSE scores were selected as the indicator for assessing changes in cognitive status for purposes of the present study.
At each visit, 26% xenon gas was inhaled for 8 minutes during serial CT brain scanning to provide an x-ray dense contrast indicator for measuring cerebral perfusion. Clinical and laboratory evaluations were determined among both groups to detect associated risk factors for stroke and adequacy of their control. Controlled risk factors included hypertension, atherosclerotic heart disease, hyperlipidemia, diabetes mellitus, and cigarette smoking.
IVD patients were not admitted until 
3 months after their last
stroke. Patients with large thromboembolic strokes >50 mm in diameter
by CT scanning and with severe neurological deficits were
excluded30 31 because aphasia, neglect, and severe motor
involvement interfere with the reliability and reproducibility of
neuropsychological testing and because large cerebral infarctions are
less remediable.
Inclusion criteria for IVD patients were (1) DSM-III-R listings for
dementia; (2) Hachinski ischemic scales >6; (3) multiple strokes by
history or neurological examination; and (4) CT confirmation of
multiple small infarctions. Exclusion criteria were (1) large
thromboembolic cerebral infarctions with major neurological deficits;
(2) CT evidence of normal pressure hydrocephalus, subdural hematoma, or
mass lesion; (3) central nervous system infections; (4) hypothyroidism;
(5) vitamin B12 deficiency; (6) Hamilton Depression Scale
score 17; or (7) drug and alcohol abuse. These criteria conform to
the criteria for probable IVD recommended by Chui et al32
and the criteria for IVD due to lacunar strokes recommended by the
National Institute of Neurological Disorders and Stroke and Association
Internationale pour la Recherche et l'Enseignement en Neurosciences
(AIREN).33
Patients with probable DAT met criteria of the National Institute of
Neurological Disorders and Stroke and the Alzheimer's Disease
and Related Disorders Association.34 DAT patients were
required to have Hachinski ischemic scores <4. Exclusion criteria were
(1) clinical or CT evidence of stroke; (2) CT evidence of normal
pressure hydrocephalus, subdural hematoma, or mass lesion; (3) dementia
after cardiac arrest or coronary bypass; (4) progressive supranuclear
palsy, Parkinson's, Wilson's, Huntington's, Creutzfeldt-Jakob,
Pick's lobar atrophy, or probable Lewy body disease35 ;
(5) central nervous system infections; (6) hypothyroidism, folic acid,
and vitamin B12 deficiency; (7) Hamilton Depression Scale
score 17; or (8) drug and alcohol abuse.
Hypertensive patients were treated with standard antihypertensive medications (calcium channel blockers, ß-blockers, angiotensin converting-enzyme inhibitors, diuretics) to maintain blood pressures at or near 150 mm Hg systolic and 90 mm Hg diastolic.36 Diabetic patients were treated with diet, oral hypoglycemic agents, and insulin. Patients with hyperlipidemia were treated with diet, lovastatin, or gemfibrozil. Smokers were persuaded to desist. The 24 IVD patients were treated daily with 325 mg aspirin (n=18) and 500 mg ticlopidine (n=6).
During CT imaging, electroencephalograms, electrocardiograms, and PECO2 were monitored and blood pressures recorded before and after each xenon gas inhalation. CT images were obtained with two high-resolution scanners (Siemens Somatom DR-H or Picker Synerview model 1200SX) standardized regularly with a phantom. Images had a 512x512 matrix and pixel size of 0.47x0.47 mm with settings at 96 kilovolts (peak), 540 mA, 8 mm thickness with 5-second scanning times for the Siemens and 130 kV(p), 140 mA, 10 mm thickness with 2-second scanning times for the Picker unit. SDs were ±0.2 Hounsfield units (HU). Lower slices were selected parallel to orbitomeatal lines from lateral views, and upper slices were selected 10 mm higher. Films were retained for repositioning in later studies at the same settings. These slices provided standard regions of interest (ROIs) throughout both cerebral hemispheres to include the frontal, temporal, parietal, and occipital cortices; caudate nucleus; putamen; thalamus; frontal, capsular and occipital white matter; and centrum semiovale.37 38 39 40
Among IVD patients, CT definitions to identify small cerebral
infarction subtypes were as follows: (1) lacunar infarctions: 
15 mm
in diameter in territories of deep penetrating arteries; (2) cortical
infarctions: superficial hypodensities involving cortex and subcortical
white matter in major cerebral arterial territories; (3) subcortical
nonlacunar infarctions: in subcortical white matter and basal ganglia
measuring >15 mm but <50 mm in diameter; and (4) border-zone
infarctions: cortical and subcortical hypodensities in border zones of
major cerebral arteries.
CT estimates of infarctions were made at study entry and follow-up, without reference to earlier records to determine numbers of "silent" as well as symptomatic cerebral infarctions.
Interval perfusions were measured at entry and follow-up during xenon gas inhalation delivered by a rapid enhancer.37 Information from CT tapes was transferred to desktop computers, and local cerebral blood flow (LCBF) and CT densities were measured directly on CT slices. Noncontrasted scans functioned as baseline, and progressively enhanced scans computed color-coded CT cerebral blood flow (CBF) maps from local tissue saturation curves.37
At each measurement, both cerebral hemispheres were cursored for 10 ROIs, including frontal, temporal, parietal, and occipital cortices; caudate nucleus; putamen; thalamus; frontal, occipital, and capsular white matter; and total cortical and subcortical gray and white matter. Infarcted volumes showing zero flow were measured as a separate variable for analysis but were excluded from regional perfusion and tissue volume measurements. Regions adjacent to the calvaria were avoided to minimize beam-hardening artifacts. We excluded cerebrospinal fluid (CSF) volumes defined as HU values <17 and calcific or bony overlaps defined as HU values >90. Mean LCBF and HU values for ROIs were summated from bihemispheric means. Annual percent LCBF changes, adjusted for differences in initial values, were calculated from annual changes in LCBF, divided by mean LCBF at entry and adjusting follow-up intervals to 12 months, as follows:
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Among IVD patients, ventricles, subarachnoid spaces, and infarcted volumes were cursored on noncontrasted CT images by summating all voxels with HU values <25 for estimating the atrophic index (ATI), since 25 HU is the established threshold for infarcted brain and CSF.38 39
Among DAT patients, ventricles and subarachnoid spaces were cursored to summate CSF voxels between 0 and 17 HU for estimating ATI.38 39 ATI was calculated as ratio of atrophic or infarcted brain volume/intracranial volumex100. ATI estimates residual cerebral parenchyma as a percentage ratio, which adjusts for differences in head size. After we adjusted for differences in initial values, annual percent changes in ATI were calculated as follows:
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Factors considered that might influence cognitive changes among IVD and DAT patients were analyzed by multiple linear regressions, with CCSE changes as dependent variables. These included total and regional cerebral atrophy, local tissue density, perfusion in gray and white matter, and size and recurrence of cerebral infarctions. Volume of infarction and leukoaraiosis were sequestered as separate variables.
We compared IVD and DAT patients using standard statistical methods including MANOVA. Mean±SD group values at entry and follow-up were compared by paired t tests.
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Results |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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No group differences were found for electroencephalograms, electrocardiograms, PECO2, or blood pressure levels during or between CT CBF measurements.
More men had IVD, and more women had DAT (Table 1
). CCSE and
Mini-Mental State Examination scores were lower and mean ages older
among DAT patients; this persisted during follow-up because there were
no dropouts. Patients with IVD had less education than DAT patients.
Hypertension, atherosclerotic heart disease, hyperlipidemia, and
diabetes mellitus were more frequent among IVD patients. Cigarette
smoking was similar between groups.
At entry, IVD patients had the following neurological deficits: (1) left hemiparesis (n=4; 16.7%); (2) left hemisensory (n=1; 4.2%); (3) combined left hemiparesis and hemisensory (n=2; 8.3%); (4) left ataxic hemiparesis (n=3; 12.5%); (5) right hemiparesis (n=5; 20.8%); (6) right hemisensory (n=1; 4.2%); (7) right hemiparesis and hemisensory (n=6; 25.0%); and (8) right ataxic hemiparesis (n=2; 8.3%).
Carotid Doppler, contrast, or MR angiography was routinely carried out among IVD but not DAT patients; occlusion or >75% intracranial stenosis of the left internal carotid artery was detected among 6 (25.0%). Follow-up neurological examinations among IVD patients improved or did not change, but DAT patients showed progressive deterioration.
At entry 94 cerebral infarctions were detected among IVD patients, including 90 lacunar, 2 border zone, 1 cortical, and 1 subcortical of the nonlacunar type. The mean number of infarctions per patient was 3.9±1.4. Locations for lacunar infarctions were as follows: (1) left caudate (n=3; 3.3%); (2) left globus pallidus (n=4; 4.4%); (3) left putamen (n=6; 6.6%); (4) left thalamus (n=1; 1.1%); (5) left frontal white matter (n=10; 11.1%); (6) left internal capsule (n=13; 14.4%); (7) left centrum semiovale (n=8; 8.8%); (8) left occipitoparietal white matter (n=1; 1.1%); (9) right caudate (n=6; 6.6%); (10) right putamen (n=3; 3.3%); (11) right thalamus (n=7; 7.8%); (12) right frontal white matter (n=13; 14.4%); (13) right internal capsule (n=6; 6.6%); and (14) right centrum semiovale (n=9; 10.0%). The mean volume ratio for cerebral infarctions was 0.65±0.3%, which did not correlate with CCSE scores.
Four IVD patients (three men and one woman; 16.7%) suffered recurrent silent lacunar infarctions detected by serial CT imaging located as follows: (1) left frontal white matter (n=2); (2) right frontal white matter (n=1); and (3) right thalamus (n=1). They were judged to be silent because clinical histories and serial neurological examinations failed to disclose new symptoms or signs, although all showed CCSE declines as follows: (1) 23 to 18; (2) 12 to 8; (3) 9 to 4; and (4) 18 to 13.
Fig 1 compares changes in cerebral ATIs during follow-up
among IVD patients (top panel) and DAT patients (bottom panel). At
entry (Table 2), ATI values were 12.1±5.4 for IVD and
8.9±2.6 for DAT patients, but during IVD follow-up (Table 3), the annual increase of ATI was +2.1%, which was
less than the +8.1% among DAT patients (P<.01). Annual
changes in volume ratios for infarctions and for leukoaraiosis did not
correlate with CCSE changes. Rapidly progressive cerebral and cortical
atrophy in DAT patients correlated directly with cognitive declines
(P<.0002, single linear regression),40 which
was not noted in IVD patients. According to MANOVA, progressive
increases in ATI were less among IVD (P=.001) than among DAT
patients (dependent variables=ATI; covariates=retest intervals, age,
CCSE scores).
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Fig 2 displays pooled regional perfusion (LCBF) values
at entry and at completion for 10 ROIs among IVD patients (top panel)
compared with DAT patients (bottom panel). Among IVD patients, LCBF
values were the same at follow-up compared with entry except for
decreases within caudate and putamen by paired t testing.
Among DAT patients, all LCBF values declined at follow-up. Among IVD
patients at entry, perfusion values within the occipital cortex and
capsular and fronto-occipital white matter were lower than in DAT
patients, but at follow-up cortical perfusion had declined only in DAT
patients.
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Table 4 summarizes LCBF regression lines, by linear
regression analyses, among IVD patients at follow-up within major gray
and white matter cerebral compartments and 10 ROIs. Only LCBF values
within subcortical gray matter declined. Annual mean percent declines
for LCBF within subcortical gray matter were -1.8% (the largest
declines were in both putamens: -2.6%). Among DAT patients, frontal,
temporal, parietal, and occipital cortical perfusion values all
declined. Annual percent decreases in cortical perfusion were as
follows: frontal, -6.5%; temporal, -6.0%; parietal, -6.2%; and
occipital, -6.8%. Annual percent values of subcortical gray matter
perfusion likewise declined in DAT patients: caudate, -4.9%;
putamen, -6.2%; and thalamus, -5.8%. In DAT patients, white matter
perfusion values also declined diffusely (4.1%) (frontal, -4.0%;
internal capsule, -3.4%; and occipital, -5.6%).
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Among IVD patients, only frontal cortical tissue density (expressed in local HU) declined at follow-up, but DAT patients showed significant declines in cortical tissue density in frontal, temporal, parietal, and occipital cortices.
Tables 5 and 6 summarize different
stepwise multiple linear regression analyses among IVD patients for
predicting bidirectional changes in CCSE scores. In analysis 1
(Table 5), which used nine demographic explanatory variables, CCSE
declines correlated directly with recurrent, silent cerebral
infarctions (P=.0031). Factors not correlating with CCSE
changes were sex, age, risk factors for stroke, and educational levels.
In analysis 2 (Table 6), increases and decreases of cerebral
perfusion within frontal white matter (P=.0001), thalamus
(P=.003), and internal capsule (P=.007)
correlated bidirectionally with cognitive improvements or declines. In
DAT patients, factors contributing to CCSE changes were similarly
analyzed, but no localized regions were found where declines in
cerebral perfusion correlated directly with cognitive deterioration,
although diffuse decreases of cerebral perfusion in DAT patients did
correlate with cognitive declines when single linear regression was
used. The statistical powers of regional results in DAT patients were
as follows: frontal cortex, P=.002; temporal cortex,
P=.007; parietal cortex, P=.009; occipital
cortex, P=.009; frontal white matter, P=.003;
occipital white matter, P=.001; putamen, P=.005;
internal capsule, P=.02; thalamus, P=.02; and
caudate, P=.03.
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Discussion |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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We detected the following differences between IVD versus DAT patients. (1) Educational levels were lower in IVD patients. (2) Risk factors for stroke (hypertension, atherosclerotic heart disease, hyperlipidemia, and diabetes mellitus) were more prevalent in IVD patients. (3) Progressive cerebral atrophy and ventricular enlargement were much greater in DAT patients. (4) Cerebral perfusion decreased progressively but diffusely in DAT patients, whereas in IVD patients only putaminal perfusion declined. (5) Age-related tissue density decreases were limited to the frontal cortex in IVD patients but also included the parietotemporal cortex in DAT patients. (6) In IVD patients, bidirectional changes in cognitive test performance correlated directly with perfusional changes within the frontal white matter, thalamus, and internal capsule. (7) Progressive cognitive declines in DAT correlated with diffuse cerebral cortical atrophy and perfusional decreases.
Although DAT patients were older and more cognitively impaired at entry and were followed up for slightly shorter time intervals, they provided annual rates of change for the variables studied for purposes of comparison with IVD patients that adjusted for these differences. One explanation for these demographic differences between the two groups may be selection of IVD patients with small strokes rather than larger cerebral infarctions.
Recurrent strokes were not recognizable clinically among the IVD group throughout 42 months of follow-up, but 16.7% developed silent cerebral infarctions by serial neuroimaging, all associated with cognitive declines. Recurrent strokes among treated IVD patients are reported to be reduced with risk factor control and antiplatelet therapy.41 Among the present treated IVD patients, 67% cognitively improved or stabilized and 33% declined, which contrasts sharply with DAT patients who cognitively deteriorated.
Among IVD patients, annual declines in cerebral perfusion were limited to subcortical gray matter, while among DAT patients there were more diffuse and severe perfusional declines. The annual rate of decline in mean cortical perfusion among DAT patients of -2.0 mL · 100 g-1 · min-1 is 13 times larger than that of -0.15 mL · 100 g-1 · min-1 reported among age-matched normal volunteers.40 42 43 44 Diffuse reduction of cortical perfusion among DAT patients has been shown by positron emission tomography scanning to result from reduction in cerebral cortical metabolic demands as a result of Alzheimer's changes.18 19 22 The present results are in agreement with previously reported annual declines of cortical perfusion in DAT patients.43 44
Among IVD patients, improvements or declines in CCSE scores correlated directly with bidirectional changes in perfusion within the frontal white matter, thalamus, and internal capsule. Furthermore, declines in cognitive performance correlated directly with recurrent silent strokes involving the same regions. The annual rate of -2.1% for overall cerebral atrophy among IVD patients is impressively less than the -8.1% measured among DAT patients. Overall cerebral atrophy in DAT is associated with marked cortical atrophy, diffuse cortical hypoperfusion, and diffuse decreases in cortical tissue density or polioaraiosis (defined as decreased tissue density measured in gray matter40 ). Polioaraiosis in IVD patients was limited to the frontal cortex, which occurs in normal aging42 and should be expected among aging IVD patients. However, temporoparietal cortical polioaraiosis appears to be a biological marker for DAT, since this is not seen in normal aging42 and was not seen in IVD patients. When the present observations are considered together, they provide evidence that cognitive impairments in IVD are due to the combined effects of cerebral ischemia and infarction and have identifiable differences in time courses compared with DAT. These differences are best detected by serial neuroimaging, particularly if accompanied by neurological and psychometric reassessments. These courses of changes over time in IVD contrast with those in DAT, in which progressive and diffuse cortical atrophy, cortical hypoperfusion, and frontotemporal and parietal polioaraiosis correlate with cognitive declines.40 45
Others have reported that regional decreases in cerebral perfusion correlate directly with cognitive declines in IVD patients, including IVD due to large strokes, in which changes in cognitive test performance correlated directly with fluctuations in cortical perfusion.46 Kitagawa et al47 also correlated deficits in cognitive test performance with declines in perfusion within the thalamus and frontotemporal cortex, and Kawamura et al23 contrasted IVD patients showing cognitive improvements with those who deteriorated and concluded that reduced perfusion values within the frontal cortex, white matter, and thalamus were responsible for cognitive declines.
Albert et al48 suggested that enlarged ventricles provide useful information for diagnosing DAT, but Wippold et al49 emphasized that DAT cannot be predicted from a single CT measurement. Present documentation of +8.1% annual rates of cerebral cortical atrophy with ventricular enlargements of +9.6% in DAT exceed those seen in IVD caused by small cerebral infarcts. Thus, repeated cerebral imaging after 6 months should estimate annual rates of cerebral atrophy among demented patients, which helps in differentiating between IVD and DAT.
Reported sites of infarctions responsible for IVD include dominant or both thalami,50 both caudates,51 52 and thalamocortical projection systems.7 47 Among 30 patients with autopsy-confirmed IVD, Ishii et al6 reported lacunar infarctions to consistently involve both caudate nuclei and adjacent periventricular frontal white matter. Rodier et al52 reported longitudinal studies in a single patient suffering progressive dementia from cumulative infarctions involving both caudates and adjacent white matter confirmed by serial neurological, psychometric, neuroimaging, and postmortem studies, and others have correlated frontal lobe infarctions with cognitive impairments.9 11
In the present investigation four IVD patients were shown by neuroimaging to have recurrent silent cerebral infarctions, all associated with cognitive declines and located in frontal white matter and thalamus. Silent strokes hasten cognitive decline by acting synergistically with earlier infarctions53 and mimic DAT since they obscure the expected stepwise progression of IVD.5
Time courses of change in IVD versus DAT confirm that annual rates of cerebral atrophy in IVD of the lacunar type are less than in DAT40 45 and do not correlate with cognitive impairments. Differences in time courses between IVD and DAT support its vascular pathogenesis and separate it from the abiotrophy of DAT. Progressive polioaraiosis of the temporal and parietal cortices is a hallmark of DAT that is not seen in IVD or normal aging.42
Bracco et al54 followed up 19 patients with cerebrovascular disease for 4 years comparing cognitive testing with leukoaraiosis and atrophy measured by serial MRI and were unable to correlate cerebral atrophy with cognitive declines. De Reuck et al26 used positron emission tomographic measurements among patients with cerebral infarctions and different degrees of leukoaraiosis and measured cerebral oxygen extraction fractions within leukoaraiotic white matter. Oxygen extraction fractions were preserved or increased in leukoaraiosis despite white matter hypoperfusion, confirming the existence of a state of reversible ischemia and "incomplete infarction" of white matter.
In our IVD patients, risk factor control plus antiplatelet treatment were routinely administered, which probably accounts for the lack of correlation between cognitive test performance and associated risk factors54 55 56 and for the clinical absence of recurrent strokes. Long-term control of risk factors, particularly hypertension, is known to improve cerebral perfusion among stroke patients,36 55 56 and aspirin or ticlopidine reduces the risk of recurrent cerebral infarctions.41 In the present study both DAT and IVD patients had risk factors controlled, but only IVD patients received antiplatelet treatment.
We conclude that recurrent, frequently silent strokes decrease cerebral perfusion within the frontal white matter, thalamus, and internal capsule, resulting in cognitive impairments. Silent strokes in IVD often mimic DAT, although serial neuroimaging will unveil this subtle cause of dementia. Clinical identification of cognitive impairments after small strokes is important because institution of secondary prevention may stabilize or improve cognitive performance.
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Acknowledgments |
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This study was supported by the Department of Veterans Affairs Central Office (Washington, DC), the Gordon and Mary Cain Foundation, and a grant from Harry K. Smith (Houston, Tex). Dianne B. Bailey processed the manuscript. Patricia M. Wills, LVN, BS, Ada Hinds, CRT, James Simon, CRT, and Diana Brigham, CRT, provided technical assistance during CT scanning. Gerald Timpe and Zihong Zhang, PhD, of Diversified Diagnostic Products (Houston, Tex) collaborated in developing the xenon enhancer and computer programming for CBF and other CT measurements.
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Footnotes |
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Reprint requests to John Stirling Meyer, MD, CBF Laboratory, Bldg 110, Room 225, Veterans Affairs Medical Center, 2002 Holcombe Blvd, 151A, Houston, TX 77030.
Received November 21, 1994; revision received February 23, 1995; accepted February 23, 1995.
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