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Stroke. 1996;27:408-414

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(Stroke. 1996;27:408-414.)
© 1996 American Heart Association, Inc.

Articles

Neuropsychological, Psychiatric, and Cerebral Blood Flow Findings in Vascular Dementia and Alzheimer's Disease

Sergio E. Starkstein, MD, PhD; Liliana Sabe, PhD; Silvia Vázquez, MD; Alejandra Tesón, PhD; Gustavo Petracca, MD; Erán Chemerinski, MD; Guillermo Di Lorenzo, MD Ramón Leiguarda, MD

From the Departments of Behavioral Neurology (S.E.S., L.S., A.T., G.P., E.C.), Clinical Neurology (S.E.S., R.L.), Nuclear Medicine (S.V.), and Neuroradiology (G. Di L.), Raúl Carrea Institute of Neurological Research, Buenos Aires, Argentina.


*    Abstract
up arrowTop
 *Abstract
down arrowIntroduction
 down arrowSubjects and Methods
down arrowResults
down arrowDiscussion
down arrowReferences
 
Background and Purpose Psychiatric, neuropsychological, and cerebral blood flow differences between patients with ischemic vascular dementia (IVD) or Alzheimer's disease (AD) were examined.

Methods A consecutive series of patients who met either the criteria of the National Institute of Neurological Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association for probable AD or the State of California AD Diagnostic and Treatment Centers criteria for probable IVD were included in the study. Twenty consecutive patients with IVD were matched for age, sex, and Mini-Mental State Examination scores with 40 consecutive patients with probable AD. Patients underwent a psychiatric interview, a neuropsychological assessment, and single-photon emission CT imaging with 99mTc-hexamethylpropyleneamine oxime.

Results Patients with IVD showed significantly more severe anosognosia (P<.05) and emotional lability (P<.01) than AD patients, but no significant between-group differences were found in the frequency and severity of depression. IVD patients showed significantly more severe deficits in tests of planning, sequencing (P<.05), and verbal fluency (P<.05) as well as significantly more severe cerebral blood flow deficits in the basal ganglia (P<.01) and the frontal lobes (P<.001) than AD patients.

Conclusions Patients with IVD showed a relatively more severe dysfunction of the frontal lobes as demonstrated by single-photon emission CT and expressed in specific psychiatric and neuropsychological changes than AD patients matched for age, sex, and severity of dementia.


Key Words: Alzheimer's disease • cerebral blood flow • dementia • neuropsychology


*    Introduction
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 up arrowAbstract
 *Introduction
down arrowSubjects and Methods
down arrowResults
down arrowDiscussion
down arrowReferences
 
While clinical criteria for the diagnosis of AD were developed more than 10 years ago,1 formal criteria for the diagnosis of IVD have only recently been proposed.2 3 However, the issue of validity still remains, and whether the criteria for IVD separate this syndrome from AD has begun to be examined only recently.

Kertesz and Clydesdale4 examined the presence of neuropsychological differences between patients with IVD and AD. They compared 25 patients with IVD (selected on the basis of having a modified ischemic score5 >=4) and 103 patients with AD. Whereas patients with IVD had significantly more severe deficits on tests tapping "frontal and subcortical mechanisms," patients with AD performed worse on tasks of verbal memory and language repetition. Powell et al6 assessed speech and language alterations in 18 IVD and 14 AD patients. They found more deficits in motor aspects of speech in IVD patients, whereas patients with AD had significantly more empty speech and anomias.

To the best of our knowledge, only one study examined psychiatric differences between patients with AD and IVD. Cummings et al7 assessed the presence of delusions, depression, and hallucinations in 30 patients with probable AD and 15 patients with IVD. Although patients with IVD had a significantly higher frequency of depression, no significant between-group differences were found in the prevalence of delusions or hallucinations.

Several studies examined the presence of CBF differences among patients with IVD or AD. McKeith et al8 carried out 99mTc-HMPAO SPECT studies in 20 AD and 20 IVD patients. Whereas AD patients had lower CBF in temporal and posterior parietal areas, patients with IVD had a proportionally lower CBF in anterior regions. Although similar findings were reported by Jagust et al9 in a study that included a small sample, Mielke et al10 could not find significant CBF differences between patients with IVD and normal control subjects.

Although these studies have advanced our knowledge of the clinical and metabolic correlates of IVD, several methodological limitations should be discussed. First, all of the above studies examined single dimensions (ie, either neuropsychiatric, CBF, or neuropsychological domains), and to our knowledge a comprehensive study assessing psychiatric, cognitive, and CBF differences in the same cohort of IVD and AD patients has not been carried out. Second, the criteria used to diagnose IVD were quite varied in the different studies, ranging from a cutoff score on the Hachinski Ischemic Scale11 to fulfilling standardized diagnostic criteria for IVD. Third, studies of psychiatric correlates in IVD used only depression scales or symptom checklists, and structured psychiatric interviews were not carried out.

The present study included a consecutive series of patients meeting the State of California AD Diagnostic and Treatment Centers criteria for probable IVD.2 Each patient with IVD was matched with two patients with probable AD for age, sex, and cognitive impairments. All patients received a comprehensive neurological, psychiatric, and neuropsychological evaluation, and a subsample was assessed with MRI and SPECT.


*    Subjects and Methods
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 up arrowAbstract
 up arrowIntroduction
 *Subjects and Methods
down arrowResults
down arrowDiscussion
down arrowReferences
 
Patients
A consecutive series of 230 patients were examined because of progressive cognitive decline in the Raúl Carrea Institute of Neurological Research. For the present study, patients were divided into two groups: (1) IVD group, patients who met the State of California AD Diagnostic and Treatment Centers Criteria for probable IVD,2 and (2) AD group, patients who met the criteria of the National Institute of Neurological Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association for probable AD.1

Neurological Examination
After giving informed consent, each patient was examined by a neurologist who was blinded to the psychiatric, neuropsychological, and CBF findings. The neurological examination was conducted with the following instruments.

Stroke Data Bank–Neurological Examination Form.12 This is a structured neurological evaluation that assesses the presence and severity of focal neurological signs such as motor and sensory deficits, language impairments, coordination deficits, etc.

Unified Parkinson's Disease Rating Scale.13 The UPDRS assesses the presence of extrapyramidal signs such as tremor, rigidity, and akinesia (scores range from 0 to 4, with 0 being normal). In patients with focal motor deficits, only the spared limbs were assessed. This scale also rates other parkinsonian signs, such as abnormalities of speech, facial expression, posture, gait, and postural stability. The UPDRS has been used previously in the assessment of extrapyramidal signs among patients with dementia.14

Psychiatric Examination
Every patient was examined by a psychiatrist blinded to other clinical or radiological findings with the following instruments.

Structured Clinical Interview for DSM-III-R.15 The SCID is a semistructured diagnostic interview for making the major Axis I DSM-III-R16 diagnoses. On the basis of the SCID responses, DSM-III-R Axis I diagnoses were made.

SCID II.15 The SCID II is a 100-item questionnaire designed to evaluate DSM-III-R personality disorders before the onset of the cognitive impairment. On the basis of these answers, a diagnosis of personality disorder was made using DSM-III-R criteria.

Present State Examination (PSE).17 The PSE is a semistructured psychiatric interview that has been used in the assessment of psychiatric disorders among patients with dementia14 15 16 17 18 and other neurological disorders.19

Research Diagnostic Criteria, Family History (RDC-FM).20 To obtain a family history of psychiatric disorders for the patients' first- and second-degree relatives, two first-degree relatives were interviewed. Diagnoses of Axis I disorders were made based on the RDC-FM.

Hamilton Depression Scale (HAM-D).21 The HAM-D is a 17-item interviewer-rated scale that measures psychological and autonomic symptoms of depression.

Hamilton Anxiety Scale (HAM-A).22 The HAM-A is an 11-item interviewer-rated scale that measures the severity of generalized or persistent anxiety.

Anosognosia Questionnaire–Dementia (AQ-D).23 This instrument consists of 30 questions divided into two sections. The first section assesses intellectual functioning, whereas the second section examines changes in interests and personality. Form A is answered by the patient alone, while form B (a similar questionnaire written in the third person) is answered by the patient's caretaker blinded to the patient's answers in form A. The final score is the difference between scores in forms B and A. Thus, positive scores indicate that the caretaker rated the patient as more impaired than the patient himself.

Dementia Psychosis Scale (DPS).24 This is an 18-item scale that quantifies the severity and types of delusions in demented patients at the time of the psychiatric evaluation.

Pathological Laughing and Crying Scale (PLACS). This instrument is an interviewer-rated scale that quantifies aspects of pathological affect, including the duration of the episodes, their relation to external events, degree of voluntary control, inappropriateness in relation to emotions, and degree of resultant distress. We have demonstrated the validity and reliability of the PLACS in AD.25

Functional Independence Measure.26 This instrument assesses self-care, sphincter control, mobility, locomotion, communication, and social cognition. Higher scores indicate fewer impairments in activities of daily living.

Neuropsychological Examination
The following tests were used in the neuropsychological examination. The MMSE27 is an 11-item examination that has been found to be reliable and valid in assessing a limited range of cognitive functions. Raven's Progressive Matrices28 assess reasoning in the visual modality. The Wisconsin Card Sorting Test29 measures the ability to develop new concepts and shift sets. The Controlled Oral Word Association Test30 examines access to semantic information with time constraint. The Trail Making Test31 examines visual, conceptual, and visuomotor tracking, and Digit Span32 examines auditory attention. Buschke Selective Reminding Test33 measures verbal learning and memory during a multiple-trial list-learning task. The delayed trial was used as the outcome measure. The Benton Visual Retention Test34 assesses visual perception and visual memory. The Token Test35 examines verbal comprehension of sentences of increasing complexity, and the Boston Naming Test36 examines the ability to name pictured objects. Block Design37 examines the presence of constructional apraxia, and Similarities37 provides a measure of abstract reasoning.

SPECT Examination
After written consent was obtained from patients, a SPECT study was carried out 1 week after the psychiatric examination as described in a previous publication.38 SPECT studies were carried out in the first 10 consecutive IVD patients and their respective 20 matched AD patients. This study was approved by the ethics review committee of the Raúl Carrea Institute of Neurological Research. We used 99mTc-HMPAO (25 mCi; Ceretec, Exametazime, Amersham International) that was injected intravenously into an antecubital vein. Patients sat with eyes closed and ears unplugged in a quiet room with dim lights. Fifteen minutes after the injection, patients were placed in a supine position with the orbitomeatal line positioned vertically, centered in the field of view. The alignment was carried out with vertical and horizontal laser beams, and the patient's head was held still by an ad hoc head holder. SPECT was carried out with a General Electric 400 AC/T rotating gamma camera attached to a Starcam 3200 computer. The resolution of the system has been measured to be 14 mm full width at half maximum in the plane of reconstructed transverse sections. A CT scan was carried out in every patient, and 5-mm-thick slices were obtained parallel to the orbitomeatal line.

SPECT studies were carried out with a high-resolution collimator and a 64x64 matrix. There were 64 images obtained over 360° degrees, with a 30-second acquisition time, and a zoom of 1.6. Processing was carried out with Butterworth filtering, a critical frequency of 0.44, and a slice width of 1 pixel. Reconstructed brain slices were then reoriented in the orbitomeatal line using the sagittal and axial views, and a set of 30 axial, sagittal, and coronal sections at 6.4-mm increments were obtained. This procedure was carried out using Starcam software (General Electric). Square ROIs consisting of 3x3 pixels (voxel [3x3x1 pixels]=2.35 cm3) were used to obtain activity ratios in axial slices, taking the cerebellum as reference. Specific ROIs were identified using the atlas of Matsui and Hirano39 and defined using each patient's CT scan. Three measurements (anterior, medial, and posterior) were carried out for each of the following cortical areas: frontal inferior (orbital), frontal superior (dorsal), temporal inferior, temporal superior, and parietal (these areas were selected because they showed the most significant perfusion changes in patients with AD40 ). These measurements were averaged for each cortical region on the right and left hemispheres. ROIs were also placed in the basal ganglia, thalamus, and cerebellum. To determine the activity ratio (brain region/cerebellum), the counts per ROI of each cortical area were divided by the average counts per ROI found in each cerebellar hemisphere in the region with the highest average count. This ratio was used as a measure of regional CBF. None of the IVD patients had lesions involving the cerebellum or crossed cerebellar diaschisis. All SPECT measurements were carried out by a neuroradiologist blinded to the clinical data. The intrarater and interrater reliabilities of these measurements have been reported previously.38

CT and MRI Examination
CT scans were carried out in all the IVD and AD patients as described above. MRI scans were carried out in the whole group assessed with SPECT. All sequences were carried out with a spin-echo technique, and 5-mm-thick slices (no gap) were obtained in the axial and coronal planes (T1 sequences [TR=640, TE=25], number of excitations=4, field of view=22, matrix=160x192) and sagittal planes (T2 sequences [TR=4000, TE=45 to 90], number of excitations=1, field of view=22, matrix=160x192) with a General Electric MR Max 0.5-T device. A neuroradiologist who was blinded to the clinical and SPECT findings assessed the presence and extension of caps and bands and white matter, basal ganglia, and infratentorial hyperintensities, which were quantified using the method of Fazekas et al.41

Statistical Analysis
Statistical analysis was carried out with univariate and multivariate (repeated measures) ANOVA and post hoc Tukey tests. Frequency distributions were calculated using {chi}2 tests and a Yates' correction for cell sizes <5. All probability values are two-tailed.


*    Results
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*Results
down arrowDiscussion
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Demographic Findings
Each of the 20 patients with IVD was individually matched with the first two consecutive AD patients with the same sex, similar age (±3 years), and similar cognitive deficits (MMSE score ±3 points). No significant between-group differences were found in any of the demographic variables (Table 1Down).


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  		Table 1. Demographic Findings

Neurological Findings
Mean scores for the UPDRS are given in Table 2Down. Six of the 20 IVD patients (30%) had mild focal motor deficits: 3 (15%) had dysarthria, 2 (10%) had visual field deficits, and 1 (5%) had limb ataxia. None of the IVD patients had a neglect syndrome. None of the AD patients had focal motor or sensory signs. An ANOVA with repeated measures for UPDRS scores (group, IVD vs AD; repeated measures, UPDRS items) showed a significant group effect (F[1, 58]=6.25, P<.01) and a significant groupxUPDRS-item interaction (F[13, 754]=2.41, P<.01). The IVD group showed a significantly higher overall UPDRS score than the AD group, and between-group differences were significant for the following UPDRS items: finger tapping (F[1, 58]=6.17, P<.01), hand movements (F[1, 58]=4.44, P<.05), leg agility (F[1, 58]=11.2, P<.001), rising from a chair (F[1, 58]=5.44, P<.05), gait (F[1, 58]=5.50, P<.05), and postural stability (F[1, 58]=4.99, P<.05). After IVD patients with motor deficits were excluded from statistical analysis, significant findings remained unchanged.


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  		Table 2. Mean Scores for UPDRS Items

Psychiatric Findings
No significant differences between IVD and AD patients were found in the prevalence of major depression and dysthymia and in scores of depression, anxiety, and delusions (Table 3Down). Moreover, there were no significant between-group differences in the prevalence of personality disorders previous to the onset of dementia or the prevalence of a positive familial history of psychiatric disorders. Patients with IVD had significantly higher scores of anosognosia (t=2.04, df=58, P<.05) and pathological crying (t=2.78, df=58, P<.01) than patients with AD. Using a cutoff of >=8 points for the diagnosis of pathological crying,25 11 IVD patients (55%) and 6 AD patients (15%) had pathological crying (Yates {chi}2=8.63, df=1, P<.01). Six of the 11 IVD patients with pathological affect had putaminal lesions, 2 had occipital lesions, and 1 had a parietal white matter lesion. Within the IVD group, 9 of the 11 patients (82%) with pathological crying were depressed compared with 2 of the 9 IVD patients (11%) without pathological affect ({chi}2=7.22, df=2, P<.001). Within the AD group, all 6 patients with pathological crying were depressed compared with 8 of the 34 patients (24%) without pathological crying ({chi}2=14.5, df=2, P<.001). Thus, in both IVD and AD groups pathological crying was significantly associated with depression.


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  		Table 3. Psychiatric Findings

Two patients in the IVD group and 2 patients in the AD group were taking antidepressants (40 mg/d nortriptyline, 25 mg/d imipramine, 100 mg/d imipramine, and 50 mg/d amitriptyline, respectively), 2 patients in the IVD group and 3 in the AD group were taking neuroleptics (0.5 mg/d haloperidol [both IVD patients], 25 mg/d thioridazine [2 AD patients], and 75 mg/d thioridazine [1 AD patient]), and 2 IVD and 6 AD patients were taking anxiolytics (1 mg/d alprazolam, 7 mg/d bromazepam, 3 mg/d bromazepam [3 AD patients, respectively], 2 mg/d lorazepam [2 AD patients], and 1 mg/d alprazolam [1 AD patient]).

Neuropsychological Findings
A two-way ANOVA with repeated measures showed a significant group effect (F[1, 58]=4.55, P<.05) and a significant groupxtask interaction (F[11, 638]=4.65, P<.0001). Patients with IVD had significantly lower scores than the AD group on the Trail Making Test (part B minus part A) (F[1, 58]=4.72, P<.05) and verbal fluency (F[1, 58]=4.71, P<.05). No significant between-group differences were found between the remaining neuropsychological variables (Table 4Down).


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  		Table 4. Neuropsychological Findings

SPECT Findings
No significant differences between IVD patients with or without a SPECT study were found on age (mean years, 72.9 versus 72.1), MMSE (mean scores, 19.1 versus 18.9), HAM-D (mean scores, 10.4 versus 10.9), anosognosia (mean scores, 26.8 versus 21.6), pathological crying (mean scores, 8.4 versus 7.1), Trail Making Test (mean scores, 419 versus 514), and verbal fluency (mean scores, 23.6 versus 23.1). Similarly, no significant differences between AD patients with or without a SPECT study were found on the above variables (age, 71.2 versus 73.2 years; MMSE, 20.0 versus 19.9; anosognosia, 12.7 versus 12.8; pathological crying, 3.8 versus 2.2; Trail Making Test, 342 versus 318; and verbal fluency, 27.6 versus 31.1).

A two-way ANOVA with repeated measures (group, IVD versus AD; repeated measures, region and side) showed no significant group effect (F[1, 28]=3.34, P=NS) but a significant groupxregion interaction (F[6, 168]=2.29, P<.05). Patients with IVD showed significantly lower blood flow in frontal regions (both inferior [P<.001] and superior areas [P<.0001]) and basal ganglia (P<.01) compared with AD patients (FigureDown). No significant between-group differences were found in the remaining brain areas.



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  		Figure 1. Activity ratios using the cerebellum as reference for specific ROIs for patients with probable IVD and patients with probable AD. Solid bars indicate IVD; open bars, AD; FRO.INF, frontal inferior; FRO.SUP, frontal superior; and BAS.GAN, basal ganglia. *IVD significantly lower than AD.

Neuroradiological Findings
Eighteen of the 20 IVD patients (90%) had one or more ischemic lesions on CT scan. Lesions involved the putamen (9 patients), corona radiata (3 patients), thalamus (3 patients), internal capsule (3 patients), occipital lobe (3 patients), caudate (2 patients), and the parietal white matter (1 patient). Ten patients had two or more lesions, which were bilateral in all of them. All 10 IVD patients who had a SPECT study had one or more ischemic lesions on the CT scan involving the putamen (5 patients), internal capsule (3 patients), corona radiata (2 patients), thalamus (1 patient), parietal white matter (1 patient), and occipital lobe (1 patient).

A two-way ANOVA with repeated measures for MRI hyperintensities showed a significant group effect (F[1, 28]=9.79, P<.01) and a significant groupxlocation interaction (F[4, 112]=7.19, P<.0001). Although the IVD group had significantly more hyperintensities than the AD group, between-group differences were most significant for white matter (F[1, 28]=9.81, P<.01), infratentorial (F[1, 28]=7.08, P=.01), and basal ganglia hyperintensities (F[1, 28]=3.57, P=.06) (Table 5Down).


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  		Table 5. MRI Findings


*    Discussion
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 up arrowAbstract
 up arrowIntroduction
 up arrowSubjects and Methods
up arrowResults
*Discussion
down arrowReferences
 
We examined the presence of significant differences in psychiatric, neuropsychological, and CBF variables between patients with IVD and AD, and there were several important findings. First, patients with IVD showed significantly more severe anosognosia and pathological crying than patients with AD matched for age, sex, and severity of intellectual impairment. Second, patients with IVD showed significantly more severe deficits on neuropsychological tasks assessing planning, set alternation, and verbal fluency than AD patients. Third, patients with IVD showed significantly lower CBF in frontal and basal ganglia regions compared with AD patients.

Before further discussion, some limitations of our study should be pointed out. First, we used strict criteria for IVD, which may have produced a biased sample of patients with "severe" IVD and may also explain the rather low prevalence of IVD in our sample of patients with dementia (9%). The second limitation is that we have no neuropathological confirmation of our clinical diagnoses, and whether the IVD or AD groups included "mixed" cases (ie, IVD plus AD) could not be determined. However, the use of standardized criteria for IVD may have limited this possibility. Third, we carried out SPECT studies in a small sample of IVD patients, and future studies should examine the validity of our findings in a larger series. While none of the IVD patients had lesions involving the cerebellum, damage to this area may potentially influence the SPECT results. However, cerebellar damage should increase (and not decrease) values of regional CBF. It may be questioned whether the MMSE is an adequate tool for assessing dementia severity in AD and IVD. However, the MMSE is the most used instrument to assess the severity of cognitive decline, and the duration of dementia was comparable in both groups. Finally, motor deficits may have influenced the performance of the IVD group on the Trail Making Test. However, to control for graphomotor speed and visual scanning, the final score was the result of subtracting part A from part B.

Few studies have examined the CBF correlates of IVD. Gemmel et al42 carried out HMPAO SPECT studies in 17 patients with AD and 10 patients with IVD. Although AD patients showed significantly more severe CBF deficits in temporoparietal regions than IVD patients, no quantitative measures of CBF were reported. Deutsch and Tweedy43 carried out xenon SPECT studies in 15 patients with AD and 15 patients with IVD matched for age and severity of dementia. Although AD patients showed significantly more severe blood flow deficits involving the parietal lobe, no consistent pattern of CBF deficits was observed in the IVD group. McKeith et al8 carried out HMPAO SPECT studies in 20 AD and 20 IVD patients and found significantly lower parietal perfusion in AD patients. One limitation of that study was that AD patients were significantly older and included significantly more females than the IVD group. In a recent study, Mielke et al10 assessed 20 AD patients and 12 IVD patients with HMPAO SPECT. While the only significant between-group difference was found in the temporoparietal cortex (lower in AD patients), the IVD group had higher MMSE scores than the AD group.

Although we could not find significant differences in temporoparietal perfusion between AD and IVD patients, the latter had significantly lower CBF in the frontal lobes and basal ganglia than the AD patients. The finding of significant basal ganglia hypoperfusion was not surprising, since 8 of the 10 IVD patients had basal ganglia and/or capsular ischemic lesions. On the other hand, the finding of frontal hypoperfusion was not related to structural damage, since none of the IVD patients had ischemic lesions involving the frontal lobes. Several methodological differences may account for the discrepancy between previous studies and the present findings. First, some studies included IVD and AD groups that were not comparable in demographic variables or the severity of cognitive impairment.8 10 Second, none of the previous SPECT studies reported the prevalence and location of ischemic lesions in the IVD group, and differences in lesion frequency, location, and cortical extension may produce different regional CBF changes. The question that now arises is why IVD patients had a significantly lower bilateral frontal lobe perfusion than the AD group. Ishii et al44 reported frontal white matter and internal capsule lesions in 30 patients with IVD and "frontal lobe symptoms" such as emotional lability, apathy, pyramidal signs, and urinary incontinence. These findings suggest that the frontal lobe perfusion deficits found in our IVD patients may be secondary to anterior subcortical lesions. We also found that IVD patients had significantly more severe white matter hyperintensities than AD patients, which may further disrupt frontal metabolism.45 Whether white matter hyperintensities in IVD are primarily located in the frontal lobes and whether there are MRI and SPECT differences between IVD patients with subcortical or purely cortical lesions should be examined in future studies. Although Rao et al46 could not find significant neuropsychological differences between individuals with or without white matter hyperintensities, leukoaraiosis in AD and IVD may be significantly associated with specific cognitive deficits, and this issue should be further examined.

Another important finding was that IVD patients had significantly more severe anosognosia than AD patients. Among patients with AD, anosognosia was reported to be significantly associated with more severe deficits in frontal lobe–related tasks47 48 and right frontal lobe hypoperfusion.38 Thus, our finding of more severe anosognosia in IVD patients may be related to more severe frontal dysfunction, as demonstrated by both more severe deficits in frontal lobe–related tasks and frontal hypoperfusion.

Patients with IVD also showed a significantly higher prevalence of pathological crying than AD patients. While this is a well-known finding among patients with IVD, this is to our knowledge the first study to compare the prevalence of pathological affect between AD and IVD patients in a systematic way. We found that in both IVD and AD groups pathological crying was significantly associated with depression (either dysthymia or major depression). However, although the prevalence of depression was similar in IVD and AD patients, the prevalence of pathological crying was significantly higher in IVD patients. Thus, while depression may be an important predisposing factor for pathological crying, other factor(s) also may be necessary. In a recent study, Andersen et al49 reported brain stem, basal ganglia, and periventricular lesions in patients with poststroke pathological crying. Most of our IVD patients had basal ganglia and/or white matter lesions, as well as significantly more severe white matter and infratentorial hyperintensities than AD patients. Thus, pathological crying in IVD may result from the presence of both a depressive affective disorder and damage to subcortical brain regions. The prevalence and correlates of depression in AD have been recently examined. In a study that included a consecutive series of 103 patients, we found that 51% showed depression (28% dysthymia and 23% major depression).50 Whereas dysthymia usually started after the onset of dementia, was significantly more prevalent in the early stages of dementia, and was associated with good awareness of intellectual deficits, major depression was associated with an earlier onset of depression, a similar prevalence across the different stages of the illness, and more anosognosia than dysthymic patients. Systematic studies of depression in IVD are lacking, and whether the mechanisms of depression in IVD or AD are similar or different should be examined in future studies.

Finally, we also found significantly more severe deficits on cognitive tasks involving set alternation, planning, and verbal fluency (which are usually considered frontal lobe–related tasks) in IVD patients compared with AD patients. In a study that compared 83 patients with AD and 42 patients with IVD, Almkvist51 found that IVD patients performed significantly worse on tests of motor and cognitive speeds than AD patients, but no significant between-group differences were found on tests of memory, visuospatial functions, and verbal ability. In a recent study, Almkvist et al52 found that patients with IVD had significantly more deficits than AD patients on tests of executive functioning, verbal fluency, attention, and motor performance. Wolfe et al53 examined 11 patients with multiple lacunes and 11 medical control subjects matched for age and education. They found that patients with multiple lacunes had significantly more severe deficits on tasks of response inhibition, mental set shifting, executive function, and verbal fluency than the control group, and they suggested that there may be a continuum of cognitive impairment in lacunar states, ranging from subtle signs of impairment of "frontal systems" to overt dementia. Mendez and Ashla-Mendez54 found that patients with IVD had significantly more deficits on unstructured tests than AD patients. Since unstructured tasks require executive abilities such as behavior initiation and maintenance, they suggested that cognitive deficits in IVD may be related to frontal-subcortical pathology. Similar results have been recently reported by Kertesz and Clydesdale.4

In conclusion, our study demonstrated that recently proposed diagnostic criteria for IVD characterize a group of demented patients with significantly more severe anosognosia and pathological crying, more severe deficits in frontal lobe–related cognitive tasks, and lower CBF in the basal ganglia and frontal lobes compared with patients with probable AD. Future studies may demonstrate whether IVD patients have a different longitudinal evolution of their psychiatric, neuropsychological, and metabolic deficits than AD patients.


*    Selected Abbreviations and Acronyms
 
AD = Alzheimer's disease
CBF = cerebral blood flow
DSM-III-R = Diagnostic and Statistical Manual of Mental Disorders, edition 3, revised
HMPAO = hexamethylpropyleneamine oxime
IVD = ischemic vascular dementia
MMSE = Mini-Mental State Examination
ROI = region of interest
SCID = Structured Clinical Interview for DSM-III-R
SPECT = single-photon emission CT
TE = echo time
TR = repetition time
UPDRS = Unified Parkinson's Disease Rating Scale


*    Acknowledgments
 
This study was partially supported by a grant from the Raúl Carrea Institute of Neurological Research. We thank J. Paul Fedoroff, MD, for his valuable suggestions.


*    Footnotes
 
Reprint requests to Sergio E. Starkstein, MD, PhD, Department of Behavioral Neurology, Raúl Carrea Institute of Neurological Research, Montañeses 2325, 1428 Buenos Aires, Argentina.

Received July 12, 1995; revision received October 12, 1995; accepted October 31, 1995.


*    References
up arrowTop
 up arrowAbstract
 up arrowIntroduction
 up arrowSubjects and Methods
up arrowResults
up arrowDiscussion
*References
 

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