METHODS

RESULTS

Group differences in language, spatial perception, and memory were analyzed using independent samples t tests. The three measures of executive functioning central to this study's hypothesis were also analyzed using t tests but to reduce the risk of a type I error, a Bonferroni correction was applied, setting α at 0.017.

Mean scores for both groups are summarised in table 1⇑. There were no significant differences between the SIVD and control groups on Boston naming, controlled oral word association test, spatial perception, and the verbal recall and recognition measures. The SIVD group performed below the level of the control group on recall of the Biber stimuli on trial 5 and again after a delay. The groups performed comparably on the delayed recognition condition.

On the Stroop test, patients with SIVD made significantly fewer correct responses than the controls on the interference condition, whereas there were no group differences on the simpler colour naming condition. Group differences on the interference condition remained significant even after entering the colour naming condition as a covariate in an analysis of variance (ANOVA). There were no group differences in the number of errors on the interference condition.

Significant group differences were also found on the number of correct sorts generated on the California card sort test. Although both groups performed in the average range, the mean number of correct sorts for the control group was almost one sort more than the SIVD group. Three of the 12 patients with SIVD performed one SD or more below the mean of the control group. There were no group differences in the number of perseverated sorts. Finally, the control group achieved significantly higher scores than the SIVD group on the initiation-perseveration subtest. Half of the 12 patients with SIVD scored 1 SD or more below the mean of the control group.

We had originally hoped to examine the number and location of lacunes within the SIVD group to see if any relations with behavioural indices could be discerned. Unfortunately, most of our sample had multiple, bilateral lacunes, which would obscure any clear brain-behaviour relations. The number of thalamic lacunes correlated with correct sorts on the California card sort test (r=−0.71; p=0.01) and with the initiation-perseveration score (r=−0.58, p<0.05). The number of lacunes in the right hemisphere also correlated with the California card sort score (r=−0.76; p<0.01). Number of white matter lacunes was negatively correlated with the Stroop interference condition, but the correlation did not reach statistical significance (r=−0.48; p=0.11). None of the correlations between white matter signal hyperintensity and cognitive ability reached significance for the SIVD group. When data from both groups were analyzed, there were significant correlations between white matter signal hyperintensity and two of the three executive function measures (Stroop interference: r=−0.46, p<0.01; card sort: r=−0.38, p<0.05) but none of the memory, language, or visuospatial measures. Exploratory analyses were also carried out comparing the six patients with SIVD with one or two lacunes with the six patients with three or more lacunes. None of the comparisons reached significance, although the group with more lacunes tended to perform less well than the group with fewer lacunes.

DISCUSSION

Results indicate that despite functioning without obvious impairment in the community, non-demented patients with subcortical lacunar infarcts exhibit subtle cognitive deficits relative to control subjects. Executive functioning may be particularly vulnerable. Patients with SIVD were slower than controls on the Stroop interference condition, generated fewer target categories on the California card sort test, and had lower scores on the initiation-perseveration subtest of the DRS. Importantly, these differences were found in a group of patients who performed at control levels on measures of global cognitive ability, verbal memory, confrontation naming, verbal fluency, and visuoperceptual skill. The current findings are consistent with other reports suggesting that subcortical vascular disease can produce cognitive changes in the absence of dementia.^21,22

Other studies of subcortical syndromes have suggested that recent memory is often impaired.^23,24 We found differences for visual memory but not for verbal memory. There are at least three possible explanations for the absence of significant differences for verbal memory in our study. Firstly, both of our subject groups were high functioning; all participants had CDR scores of 0 and the mean level of education for both groups was over 15 years. Thus, it is possible that the degree of subcortical pathology, although enough to disrupt executive functioning, was insufficient to produce verbal memory impairment. A second possible explanation is that our sample of patients with SIVD was small, and we lacked sufficient statistical power to detect significant differences. A review of our data indicates that the SIVD group performed almost 0.5 SD below the level of the control group on verbal delayed recall, suggesting that there may be small differences in memory that would have been detected with a larger sample. A third possible explanation for the discrepancy is that the visual memory test is a more novel and difficult task, and thus would be more sensitive to mild, non-specific declines in episodic memory.

The term “executive functioning” has been used to refer to a host of cognitive abilities, including conceptual reasoning, inhibition of overlearned patterns of behaviour, inhibition of responses to salient stimuli, mental flexibility, set shifting, organisational ability, planning, regulation of working memory, and fluency of thought. The Stroop interference condition requires examinees to inhibit an overlearned reading response in order to name the colour of ink in which the word is printed. Patients with SIVD were slower than controls, although there were no group differences in the number of times participants incorrectly read the stimulus item. It is unlikely that the Stroop results can be explained solely on the basis of slower response speed, as there were no group differences on the colour naming condition. However, given that several studies have reported slower information processing in subcortical patients^25,26 and patients with frontal strokes,²⁷ direct assessment of processing speed changes and the role of task difficulty in SIVD is warranted.

Subjects with SIVD also demonstrated subtle difficulties with conceptual reasoning, as reflected in their fewer correct sorts on a card sorting task. These data are consistent with the findings of Dimitrov et al who reported that non-demented patients with Parkinson's disease had problems with concept formation.²⁸ Verbal fluency, another measure sensitive to subcortical-frontal system pathology, was unimpaired in our sample, although Bondi et al have found that parkinsonian patients have verbal fluency deficits.¹ As with the memory data, the absence of significant group differences on verbal fluency in our study may be related to our patients being less impaired than those of Bondi et al or to small sample size. Whether additional aspects of executive functioning are compromised in SIVD warrants further study; set shifting deficits, for example, have been reported in other subcortical syndromes, even in the absence of dementia.²⁹

Some controversy exists regarding the relation between white matter signal hyperintensities and cognitive function. Wahlund et al³⁰ found no significant correlations between the degree of or increase in signal hyperintensities and results from any of the neuropsychological tests. By contrast, other studies have suggested a relation in elderly adults without dementia.^31–,³³ White matter foci in periventricular and subcortical regions have been found to be related to memory,^32–,³⁴ executive skills,^33,34 and global cognitive ability.³³ In the present study, the extent of white matter signal hyperintensity was found to be correlated with two of the three executive measures but with none of the other neuropsychological variables.

The presence of a decline in executive functioning without measurable changes in global cognitive abilities, verbal memory, confrontation naming, verbal fluency, or visuoperceptual skill, is most consistent with a subcortical-frontal model for SIVD. However, we cannot state with certainty that frontal structures are definitely affected after subcortical lacunes in the absence of pathological confirmation or in vivo evidence from structural or functional imaging. In other subcortical syndromes, however, metabolic changes in the cerebral cortex have been documented using PET. In patients with multiple sclerosis, for example, there are widespread reductions in cortical metabolism that are most striking in the superior mesial frontal cortex and superior dorsolateral frontal cortex.³⁵ Similarly, frontal hypoperfusion has been documented in progressive supranuclear palsy and Parkinson's disease.^36,37 Cortical changes in regional cerebral blood flow and cerebral metabolic rate for oxygen have also been reported in patients with dementia or mild cognitive impairment secondary to lacunar infarcts.^38–,⁴⁰ The patterns of hypoactivity are often generalised without frontal prominence, however, and patients used in these studies are more compromised than those in the present study. Consequently, the evidence that the subtle cognitive changes we found in our patients with lacunes is due to disruption of subcortical-frontal circuits is primarily behavioural and awaits further confirmation.