Gait Pathway in Subcortical Vascular Dementia and in Alzheimer’s Disease
Open access peer-reviewed chapter
By Rita Moretti, Arianna Sartori, Beatrice Baso and Silvia Gazzin
Submitted: June 16th 2014Reviewed: November 5th 2014Published: July 1st 2015
Gait impairment, worse equilibrium scores and falls are associated with leukoaraiosis, as widely recognised [1-6]. In Binswanger’s disease with a severe leukoaraiosis gait disorders are clearly evident while patients with mild periventricular changes may present subclinical forms of gait disorders, as proposed by some authors (see data in ).
Gait disorders in the elderly are particularly relevant, since they can influence the loss of functional independence and death .
As anticipated, cerebral small vessel disease (both white matter lesions and lacunar infarcts) correlates with gait parameters: stride length and a lower gait velocity .
Most importantly, subcortical vascular lesions seem to increase the possibility of falls, even if clear evidences are still lacking [9-11].
Walking difficulties in Alzheimer’s disease are well described : patients show slow and irregular steps, difficulties in turning and avoiding obstacles [13, 14]. These disturbances have been described also in patients free from extrapyramidal, ataxic, paretic signs, and clinically relevant musculoskeletal impairments [12, 14].
Moreover, Alzheimer’s disease patients have a worse balance [12, 14, 15] and a higher risk of falls compared with matched controls [16, 17]. The prevalence of gait abnormalities varies widely across the studies (from 8.7%  to over 90% ); this can be explained because of different inclusion criteria and/or assessment procedures.
These observations have been confirmed by studies demonstrating that patients with Alzheimer’s disease walk more slowly compared to healthy controls  and these gait problems have been interpreted as manifestations of the extrapyramidal deficits (well-known to affect 12–28% of Alzheimer patients), or as side effects of drug treatment (e.g. neuroleptic agents) .
Since a overt walking problems and trunk movement alterations can be seen also in absence of extrapyramidal signs, it has been proposed that some Alzheimer’s disease patients may present “frontal gait disorder”, a syndrome coterminous with gait apraxia [21, 15].
The lack of a standardised instrument to assess gait has been implicated as a possible cause for the low frequency of reports on the topic.
Since the walking assessment cannot discriminate between walking disorders caused by gait apraxia and other neurological causes of walking difficulty, there has been the necessity to exclude alternative causes of walking abnormalities in Alzheimer’s disease (overt extrapyramidal impairments or other concurrent neurological diseases); in order to assess gait capacity, a new test has been proposed and a large proportion of the sample (40%) scored below cut off, even if the percentage of severely impaired was smaller. Although the possibility of right–left confusion, working memory deficits, and problems with verbal comprehension was minimised by demonstrating the items, the complexity of some of them might have contributed to inflating the proportion of patients performing poorly. Even though, the presence of associated vascular pathology in a few patients also cannot account for the outcome. Neuroradiological signs of white matter changes were reported in three of the 24 patients (22.5%) in the Della Sala et al.’s study , who scored below cut off in the assessment of walking skills.
Therefore, in a well-defined population suffering from subcortical vascular dementia and Alzheimer’s disease (standing from a neurological, clinical, and radiological criteria), we tried to explore gait, balance and equilibrium alterations, and a behavioral complex symptom, such as apathy, even considering precipitant factors, such as concomitant pathologies and consequent therapies. We now present an extension of the work, with a speculation on what we observed for a two-year follow-up.
From June 1st 2010 to June 1st 2013, 155 patients diagnosed with Alzheimer’s disease (AD), according to NINDCS-ADRDA criteria , and 673 patients with subcortical vascular dementia (according the NINDS-AIREN criteria for probable VaD ) (age 65–94 years) have been examined in Cognitive Disorder Unit Evaluation of the University of Trieste and enrolled in the present study.
The inclusion criteria were a Mini-Mental State Examination (MMSE) scores of at least 14 and satisfying the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria for dementia.
As far as neuroimaging is concerned, subcortical VaD (sVAD) was diagnosed when the CT/MRI scan showed moderate to severe ischemic white matter changes  and at least one lacunar infarct.
In order to be enrolled into the study, Alzheimer’s subjects had to show on brain MRI the classical pattern of atrophy of AD (hippocampal atrophy) and display hypoperfusion in temporoparietal and precuneus regions (AD) on HMPAO-SPECT.
The neurologist (RM) assessed independently, after the radiologist’s opinion, brain CT and/or MRI images and all the diagnoses have been confirmed after a long term clinical follow-up (12 and 36 months).
Exclusion criteria were: normal pressure hydrocephalus, diagnoses of major stroke or brain haemorrhage, previous brain tumours, white matter lesions due to specific aetiologies (e.g. multiple sclerosis, vasculitis, brain irradiation, and genetic forms of vascular dementia such as CADASIL or CARASIL).
Finally, also major psychiatric illness (e.g.. schizophrenia, bipolar disorders, psychosis, compulsive-obsessive disorders, etc) or central nervous system disorders and alcoholism were excluded.
Also absence of an informed caregiver, unavailability of neuroradiological examination, and/or the use of psychotropic drugs within two months prior to the clinical assessment implied patient’s exclusion from the study. According to these exclusion criteria, 27 AD patients and 70 sVAD patients were excluded.
We did not consider a discriminant/exclusion criteria depression, referring to different studies (such as ), according to the potential correlation to vascular dementia predisposing factor.
This was a prospective cohort study, designed to investigate behavioural alterations, and in particular apathy of a AD and of a sVAD population. Study subjects underwent the following evaluations.
The standardized baseline assessment implied a detailed history, physical examination (pulse rate and rhythm, blood pressure, heart size and sounds, peripheral pulses, retinal vessel and carotid artery evaluation), EKG, chest X-ray, laboratory tests and psychiatric evaluation.
All patients were followed with neurological examinations scheduled every four months, while the complete neuropsychological examination was conducted at baseline and at 36 months. We conducted the study in accordance with the Declaration of Helsinki and with the Ethics Guidelines of the Institute.
All patients were studied, with complete neurological and neuropsychological examinations.
Main outcomes of the study were: global performance, which was assessed using the Mini Mental State Examination , Frontal Assessment Battery (FAB) ; global behavioral symptoms, assessed by the Neuro Psychiatric Inventory, NPI ; the caregiver stress, assessed by the Relative Stress Scale, RSS .
In addition to these main outcome measures, the Clinical Insight Rating Scale (CIR)  (which provides a measure of its four comprising items – awareness, cognitive deficit, disease progression and functional deficit) was performed.
The Barthel index (BI)  and the Instrumental activity of Daily living (IADL)  have been used to assess functional activities and complex activities of daily living, respectively. Mobility problems were evaluated by the Tinetti scale for equilibrium/balance and gait : in particular, a semiquantitative assessment was used, consisting of the modified Tinetti test with 17 items, 9 for body balance (0-16), 8 for gait (0-12). Patients were registered for their medical intake.
Statistical analyses were performed using the Statistical Package for the Social Sciences (SPSS, version 16.0). Wilcoxon Signed Ranks test was used to analyze the Within-group changes, from baseline to 24 months, of the overall scores for each efficacy variable.
Behavioral outcome measures, cognition, Tinetti scale, global, balance and equilibrium, and BI correlations were analyzed applying the Spearman's rank correlation analyses.
The study subjects were 128 AD patients and 603 sVAD patients. All the patients could be fully studied (mean age 72.3 ± 7.3 years, range= 62-94 years). 1 AD patient and 5 sVAD patients died during the two-year follow-up. As anticipated, the diagnosis clinical history, neuropsychological assessment and neuroimaging was reinforced by subsequent follow-up in all cases.
All the selected patients underwent neuroimaging: 128 AD patients did MRI studies; 603 sVAD patients did CT scans; moreover, 201 of the latter completed the diagnostic pathway with MRI images, in case of not adequate imaging acquisition or not convincing data. Therefore, the patients who did CT/MRI were homogeneously recruited and no demographical/social/cultural/clinical difference distinguished from each other.
A neurologist (RM) revised all the imaging, employing the Blennow et al.  scale for CT scans and the Scheltens et al.  scale for MRI imaging in sVAD patients and Wahlund et al. , Kantarci et al.  and den Heijer et al.  criteria for AD MRI imaging. There was 95.8% inter-rater agreement for the independent assessment of the scans (kappa=0.8).
Patients were allowed to continue any previous therapy (e.g. antihypertensive, antidyslipidemic, antidiabetic drugs). During the follow-up, the patients were prescribed neuroleptics and/or benzodiazepines.
A synopsis of the cognitive performances obtained by the two groups has been reported in Table 1-2-3-4.
|MMSE||25.8 (2.4)||19.9 (1.9)|