Cognition in advanced normal pressure hydrocephalus: A pilot study from South India
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/neuroindia.NI_1219_15
Source of Support: None, Conflict of Interest: None
Keywords: Advanced, cognition, normal pressure hydrocephalus
Studies on advanced dementia from the western world are mostly based on patients residing in nursing homes., Unfortunately, nursing homes for patients suffering from advanced dementia are sparse in our country, and hence literature on advanced dementia is less. Considering the difficulties in examining patients at home, data on advanced dementia are better collected from hospital-based cohorts. Normal pressure hydrocephalus (NPH) is considered to be a treatable form of dementia by some medical practitioners, even though others question even the existence of such an entity. However, recent literature states that the prevalence of NPH is high in the community and remains widely under-diagnosed. Literature on cognition in NPH is sparse and more so on cognition in advanced NPH. This study was conducted with the aim to study the cognitive profile in a hospital-based cohort of cognitively-advanced NPH patients.
Patients with a diagnosis of possible or probable NPH as per the consensus criteria were selected for the study. The patients included were those availing dementia care service from three different tertiary care centers during three different consecutive periods adding to a total period of 5 years from 2010 to 2014.
Patents were considered to have cognitively-advanced NPH if the ACE score was 50 or less. In addition to ACE, patients underwent neuropsychological evaluation including digit forward test, Trail A and Trail B, Rey auditory verbal learning test (RAVLT), hospital anxiety and depression scale (HADS), Cambridge behavior inventory (CBI), informant questionnaire for cognitive decline in the elderly (IQCODE), scale for activities of daily living (ADL), and story recall test. All patients underwent mandatory investigations for treatable dementias which included thyroid stimulating hormone assay, venereal disease research laboratory (VDRL) test, and human immunodeficiency virus (HIV) screening. The available imaging of all the patients was reviewed and the option of cerebrospinal fluid (CSF) tap test was discussed. The duration of illness was ascertained from history. The cognitive scores were compared with 15 patients who were suffering from advanced AD. Verbal informed consent was obtained from all patients.
Statistical calculations were done using the Statistical Package for the Social Sciences (SPSS, IBM Corp., Armonk, New York) for Windows. For comparison of significant difference between groups, analysis of variance (ANOVA) test was used. Testing for correlation was performed using the Pearson's correlation. A P value of less than 0.05 was considered to be significant.
Eight hundred patients were evaluated for dementia during the study period. This included patients attending the outpatient clinic of the Department of Neurology and the patients admitted to Neurology wards, as well as the patients admitted under other departments, such as Orthopedics, Nephrogy, and Medicine departments. Dementia was confirmed in 326 cases. Of those patients with dementia, 193 (59.2%) were diagnosed with NPH, 77 (23.6%) with AD, 29 (8.9%) with FTD, and 27 (8.3%) with vascular dementia, based on the respective criteria.,,, Of the 105 patients with an ACE score of less than 50 (advanced dementia), the diagnosis was unequivocal in only 45 patients. Of these patients, a detailed neuropsychologic assessment could be done in 23 patients with NPH and in 15 patients with AD. These were the patients selected for the study. Their mean age was 72.06 ± 9.62 years. Thirteen (56.5%) patients were males, and their mean education in the number of years was 7.74 ± 3.21 years. The mean duration of illness at the time of presentation was 2.73 ± 2.72 years. As many of these patients were not earlier evaluated for dementia, the time of onset of illness was ascertained from history. Onset of impairment of activities of daily living or of occupational functioning was taken as the onset of illness. All the patients had gait apraxia.
All the patients underwent the Addenbrooke's cognitive examination using a version standardized and validated in the local population., The mean mini–mental state examination (MMSE) score was 11.6 ± 5.2 and mean ACE score was 27.26 ± 1.3. As per the norms available for the local population, the mean MMSE score for education of 5 to 8 years was 21.9 ± 3.7 and ACE score 62.6 ± 11.4, thereby indicating that the patients had advanced dementia. For the purpose of comparison, the ACE subscores were converted into percentage of maximum score (PMS). Since the total ACE score was 100, the ACE PMS was 27.26 ± 1.3. The cognitive domains analyzed were memory, orientation, language, and executive function. The domain that was the most severely impaired was memory (mean score: 6.7 ± 4; PMS: 19.41 ± 11.58) and the least affected cognitive domain was language (mean score: 15.56 ± 8.25; PMS: 37.06 ± 19.63) [Table 1]. The scores were compared with the scores of 15 patients with advanced AD diagnosed as per the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) criteria, 1989. The patients were matched for age and sex education and duration of illness. No significant difference was seen between the two groups in the MMSE score, ACE score, or cognitive subscores (ANOVA, P > 0.05) [Table 1]. No correlation was seen between the duration of illness and cognitive composite score or subscores. However, age was found to correlate negatively with the memory subscore (Pearson's correlation, P = 0.013).
Attempts at characterization of cognition in NPH have met with varying observations. However, there is scant literature on cognitive abnormalities in advanced NPH. Baseline information of cognitive function helps in a better clinical diagnosis of the disease. It may also serve as the baseline clinical status against which clinical improvement can be assessed after a cerebrospinal fluid shunt treatment. This is the first study on cognition and neurobehavioral abnormalities of NPH patients from this part of our country. In this cohort of hospital-based patients, the proportion of patients with NPH was much higher than those with AD. This may be partly because of the predominance of motor involvement of patients with NPH. In a situation where awareness of dementia is less, demented patients may get neurologic attention only if they have other neurologic problems such as motor impairment.
The duration of illness was rather short for the extent of cognitive impairment. The duration of illness was ascertained from the history of the patient in a retrospective manner, and hence an ascertainment bias needs to be considered. A direct relation between the duration of illness and the severity of cognitive impairment has not been proven unequivocally in NPH. In AD, however, this association is more likely. However, we do not have studies in our population supporting this association. In our cohort of AD patients, the duration of illness appeared rather short for the severity of cognitive impairment. An ascertainment bias could be considered as a cause for this short duration of illness as patients belonging to both the categories showed a rapid progression of cognitive dyfunction. However, a prospective study in this direction is warranted in patients with NPH based on this observation.
In spite of evaluating a very high number of patients with dementia, a proper neuropsychological evaluation could only be done in a very small proportion of patients. The most common cause for not doing a neuropsychological evaluation in this cohort was poor cooperation from the patient or relative. This is partly because of ignorance on the part of the relatives regarding the the illness and the neuropsychological testing required for it. The second common cause was inability of the patient to cooperate due to the associated medical illness.
This is the first study on the cognitive profile of NPH patients from our part of the country. We included only patients in whom ACE could be administered properly. The cognitive profile of this cohort of NPH patients appeared similar to that of patients with advanced AD. This may indicate that the cognitive abnormality in NPH may not be fully explained by the hydrocephalus.
Due to the fact that the performance was poor in ACE, a detailed testing of different cognitive domains was not done as the flooring effect was expected. Hence, the subscores of ACE pertaining to each cognitive domain were analyzed. As the absolute score of each cognitive domain differed in ACE, for the purpose of comparison, they were all converted to the percentage of maximum score. The mean percentage of maximum score was 27.26 ± 1.3, thereby underscoring the difficulty in performing a detailed cognitive assessment.
Traditionally, cognitive impairment in NPH has been considered as subcortical, thereby implying that frontal dysexecutive symptom is the dominant one. However, in the recent study by Saito et al., cognitive impairment in NPH was found to be similar to AD. However, the mean MMSE score in their cohort was 21 in both the groups, thereby implying an early stage of the disease.
This study, however, has its limitations. The sample size was small and hospital based. ACE was designed as a screening instrument to pick up early dementia, and hence its utility in characterizing advanced dementia may be questionable. However, because the mean score was 27 percent of maximum, it can be inferred that the flooring effect did not affect the present study. The result has to be replicated in a larger number of patients to draw firm conclusions.
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