In subcortical vascular encephalopathy (SVE) gait disturbance is a common and early clinical sign which might be used to monitor disease progression. In the absence of reliable scales and with regard to the equivocal results of highly complex gait imaging devices we assessed the natural course of SVE in a prospective study, using a new straight forward technique to quantify and compare sequential gait studies. We report the results of 300 computerized gait analyses in 119 patients with SVE and 63 age-matched controls. Thirty-nine SVE patients were re-evaluated to monitor the natural course of the disease and to study the correlation of gait disturbances with MRI changes and neuropsychological findings. The system consists of a set of shoes containing 16 load sensors and a measuring-unit reading each sensor at 20-ms intervals. By off-line analysis we graded each recording on a Gait Disorder Score (GDS) with six variables indicating gait steadiness: step frequency, length of gait lines (which represent the movement of the centre of gravity during heel to toe movement), length of single support lines, variability of single and of double support lines, and double support time. In cross-sectional analysis, patients with SVE showed cadence (steps/min) to be reduced at 87.3 +/- 19.5 (96.4 +/- 7.8 in controls, P < 0.05). Length of gait lines was significantly less: 0.70 +/- 0.13 vs. 0.80 +/- 0.05 in controls, with length of single support gait lines reduced at 0.42 +/- 0.14 in SVE (0.58 +/- 0.06 in controls, P < 0.05). Variability of both single support lines (5.69 +/- 1.90%; 4.24 +/- 1.07% in controls, P < 0.05) and double support lines was elevated (3.59 +/- 1.62% vs. 2.54 +/- 0.59%), while duration of double support phases was increased (0.19 +/- 0.10 s vs. 0.13 +/- 0.02 s in controls, P < 0.05). The progressive character of the disease was demonstrated by increasing GDS values in 39 SVE patients with a frontal gait disorder who were re-investigated after a mean interval of 26 months (5.4 +/- 4.5 vs. 8.4 +/- 5.5, P < 0.05). This study shows the value of a new and practicable gait analysis system for the evaluation of gait disorders and it quantifies the deterioration of gait in SVE patients.

The objective of this study was to correlate clinical and brain imaging findings with walking inabilities in patients with possible vascular dementia. For 24 patients with suspected initial vascular dementia according to DSM-III-R, structured neurological, neuropsychological and neuroimaging (magnetic resonance tomography) examinations were evaluated alongside computerized gait analysis. All patients revealed an increased variability of gait lines of various degrees: mild (11%), moderate (32%) and severe (57%). Lateralization of gait patterns was present in 68% and bipedal instabilities of posture in 54%. These findings were significantly correlated with frontal periventricular white matter lesions (WMLs), which probably affect the thalamo-cortico-mediocapsular pathways. The association of gait abnormalities with WMLs of the frontocentral subcortical and periventricular territories in patients with possible vascular dementing illnesses may be used as an early indicator of the disease for follow-up and treatment trials. However, since the degree of gait impairment varies considerably relative to the common mild intellectual limitations, these structural lesions are unlikely to be directly related to the dementing process.

Apoptotic cell death is thought to be the most likely mechanism of cell death contributing to neurodegeneration in Alzheimer’s disease (AD). Here, we provide evidence that in sporadic AD cases the vulnerability of peripheral cells to undergo apoptosis is increased compared to non-demented elderly controls and, very importantly, to patients with subcortical vascular encephalopathy (SVE) as another, but demented control group. Quiescent ‘native’ and ‘activated’ lymphocytes from AD patients that were predisposed to commit apoptotic cell death by priming the cells with interleukin-2, are shown to accumulate apoptosing cells to a significantly higher extent in spontaneous and in oxidative stress-induced in vitro apoptosis. Our results demonstrate robust differences in cell death sensitivity between AD and vascular dementia. In none of the conditions investigated, lymphocytes from SVE patients were significantly different from non-demented controls. The comparable findings of a higher extent of apoptotic features in neurons and in peripheral blood cells of AD patients are remarkable and may suggest a rather general modulation of apoptotic mechanisms by the disease, which even can be picked up at the level of peripheral lymphocytes under specific in vitro conditions.

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Previous cross-sectional studies in patients with subcortical vascular encephalopathy (SVE) have shown little or no correlation between brain lesion load and clinical disability, which could be due to the low specificity of T2-weighted MRI. Recent studies have indicated that T1-weighted MRI may be more specific than T2-weighted MRI for severe tissue destruction. We studied 37 patients with a diagnosis of SVE and 11 normal controls with standardised T1- and T2-weighted MRI. All patients underwent detailed clinical assessment including a neuropsychological test battery and computerised gait analysis. Both the T2- and T1-weighted total MRI lesion loads different between patients and controls different, particularly T1. The ratio of T2-/T1-weighted lesion load was lower in controls than in patients. There was no overall correlation of T1- or T2-weighted lesion load with clinical disability, but group comparison of patients with severe and mild clinical deficits showed different lesion loads. We suggest that T1- and T2-weighted MRI lesion loads demonstrate relevant structural abnormality in patients with SVE.