Bladder and bowel incontinence frequently appears in the late stages of dementia, [1,2] probably due to loss of prefrontal control over the voiding reflexes. [1,3] Loss of sphincter control is considered to be a hallmark of moderate or severe dementia and is an item included in many functional assessment tools. [4,5] However, the relationship between cognitive decline and incontinence is not simple, [6] and little is known about their temporal pattern of evolution in different types of dementing illnesses.
Urinary incontinence is a marker of early vascular dementia, [7] and it is a secondary item in the two recent proposals of criteria for the clinical diagnosis of vascular dementia, [8,9] and in the clinical criteria of ``Binswanger's disease.'' [10] However, early incontinence could be also present in Alzheimer's disease (AD) with associated vascular lesions or in other dementing illnesses and could mislead in the identification of vascular dementia.
Urinary incontinence is a conspicuous and troublesome event [11] and may represent a general marker for the staging of dementia. It could be used as an end point in clinical and therapeutic longitudinal studies, provided it was determined that the development of incontinence relates to cognitive decline in a well-defined way.
We addressed these issues in a series of demented patients from a longitudinal prospective study followed until their death, whose onset of bladder incontinence was clearly specified in clinical records and in whom we obtained a definite pathologic diagnosis. We studied the time of urinary incontinence in several types of dementias and the relationship between cognitive performance and loss of bladder control. We anticipated that cognitive decline and incontinence would have different patterns of evolution in separate dementing illnesses.
Methods.
Patients.
Eighty-three consecutive patients included during 1986 to 1993 in the pathologic files of the University of Western Ontario Dementia Study were selected for a clinicopathologic study. They were selected because on pathologic examination they had senile plaques (SP), neurofibrillary tangles (NT), Lewy bodies (LB), and/or chronic cerebrovascular lesions (VL). In all cases, other associated pathologies, as well as heavy alcohol consumption, had been ruled out.
All patients had joined the Dementia Study after informed consent from themselves, their caregivers, or both. At the inclusion in the Dementia Study, an experienced neurologist recorded demographic and clinical data, applied a neurologic and mental state examination, and performed a routine complementary workup (hemogram, serum biochemistry, thyroid hormones, luetic serology, EEG, and CT). A cognitive examination with the ``Extended Dementia Scale'' (EDS) [12] and a functional assessment with the ``London Psychogeriatric Rating Scale'' (LPRS) [13] were also done. All cases were diagnosed as having dementia according to DSM-III criteria, [14] and this diagnosis was confirmed during a follow-up of 5.6 plus minus 2.5 years (range 1 to 12 years) until death. In most patients, the EDS, when it was possible, and the LPRS were applied every 6 to 12 months.
Clinical study.
Clinical records before death were blindly and independently reviewed, and the following data, recorded prospectively, were obtained for this analysis: age, sex, years and level of education, date of onset of dementia according to the caregivers information, date of death, time of evolution, and all the scores obtained in the EDS and LPRS during the evolution of dementia. The reviewer scored retrospectively every case with the Clinical Dementia Rating at one or more stages of evolution, when there was enough clinical information.
The onset of bladder incontinence was established within a definite year according to the longitudinal LPRS raw data; it was operationally defined as the time when the score in item 15 (``The patient is incontinent of urine or feces, or both'') changed from 0, almost never (less than once per week), to 1, sometimes (once or twice per week), or 2, almost always (three times per week or more often). In some cases, the LPRS of the precise time was not available, but the caregiver's information about incontinence had been clearly stated and recorded. The revision of LPRS and clinical records was focused on the information about incontinence excluding any peripheral or urologic causes and disregarding other clinical data with potential diagnostic clues and confounding effects.
In 69 cases, the date of onset of regular bladder incontinence was clearly stated in the clinical records. In another five cases, there was fluctuating incontinence during several months or years, and the final date was entered. Three cases without incontinence during their lifespan and seven cases without adequate data about incontinence onset were excluded. Therefore, 73 cases were used for this study.
Pathologic study.
In all cases, the brain had been obtained at autopsy and histologic sections from 10 regions (frontal, parietal, occipital and temporal lobes, hippocampus, amygdala, basal ganglia, thalamus, midbrain, and cerebellum) had been stained with hematoxylin and eosin (H-E), Bielschowsky's method, and congo red. In 47 cases, additional sections were immunolabeled as previously described [15] with an antibody to ubiquitin (Sigma Immunochemicals, St. Louis, MO). This immunostain facilitated the recognition of cortical Lewy bodies [16] and abnormal neurites in CA2. [17]
In addition to the whole histologic examination, several quantitative studies were done in one left or right randomly selected temporal section. In one slide stained with Bielschowski's method, neuritic SP and NT were counted in a 0.5-mm-wide strip of neocortex located in the depth of the external lip of the collateral sulcus. In the same slide, stained with H-E, LB were counted in a 1-mm-wide strip of paleocortex located in the middle of the parahippocampus. All measures were done by the same researcher using a reticule of 0.5 times 0.5 mm and counting all lesions partially or totally included in it.
Diagnostic groups.
On the basis of histologic examination performed without knowledge of clinical information or diagnosis, patients were sorted in diagnostic groups defined by the following criteria, partially based on Dickson et al. [16]
1. AD (29 cases): abundant neocortical neuritic SP and NT (eight or more in 1 mm2 of the temporal neocortex), as described and illustrated by Mirra et al., [18] and no abnormal ubiquitinated neurites in CA2.
2. Diffuse Lewy body disease (DLBD) (11 cases): numerous cortical (five or more in 2 mm2 of the parahippocampal cortex) and subcortical LB, abnormal ubiquitinated neurites in CA2 and different amounts of diffuse SP, without NT or neuritic SP (no more than one NT or four neuritic SP per mm2 of temporal neocortex).
3. AD plus LB (13 cases): both numerous neuritic SP, NT (eight or more in 1 mm2 of the temporal neocortex), and LB (one or more in 2 mm2 of the parahippocampal cortex) present in the cortex.
4. AD plus VL (20 cases): this somewhat heterogeneous group includes patients with mixed degenerative and vascular lesions. They had enough neuritic SP and NT (eight or more in 1 mm2 of the temporal neocortex) as to state the diagnosis of AD, but they also had moderate microscopic (4 cases) or macroscopic (1 to 6 mL of volume, 9 cases) lacunes in basal regions, moderate infarcts in left frontotemporal region (30 and 27 mL of volume, 2 cases), marked white matter hypodensities (5 cases), and hippocampal sclerosis, probably of ischemic cause [19] (1 case).
All pathologic diagnoses were independently established by two of the authors (T.D.-S. and D.M.) and the discrepancies (10% of cases) were resolved by consensus.
Statistical analysis.
The age at different clinical points (onset of dementia, onset of incontinence, death), the durations of dementia and incontinence, and the delay from dementia onset to urinary incontinence were compared between the four diagnostic groups with a one-way ANOVA. The scores in the EDS and LPRS at the onset of incontinence were also analyzed.
The consecutive scores in EDS were plotted against time of evolution of dementia before and after the onset of incontinence for a qualitative analysis. The mean scores in the EDS for every stage of the Clinical Dementia Rating were calculated in every group and compared between them.
For the intergroup comparisons after the ANOVAs, the Newman-Keuls test [20] was used.
Results.
Men predominated among DLBD patients and women among AD plus VL cases in a significant way (chi2 equals 8.885, df equals 3, p equals 0.03) Table 1.
Table 1. Pathologic diagnosis, sex, age, and duration of dementia and bladder incontinence
Patients with AD plus VL were older than the other groups at the onset of dementia and at death, but they differed significantly only from AD cases in the age at the death. The duration of dementing illness was significantly shorter in DLBD cases Table 1.
The onset of bladder incontinence in the course of dementia was significantly earlier in DLBD patients than in the other groups Table 1. This difference was not explained by other variables such as sex, age, or prior education. In a two-way (group and sex) ANOVA, neither sex nor its interaction with the diagnosis had any significant effect (F group, 4.317, p equals 0.009; F sex, 0.060, NS; F interaction, 0.029, NS). Although AD plus VL patients were older at the onset of bladder incontinence Table 1, when the effect of age was controlled for in an ANCOVA, the adjusted mean delays of incontinence onset remained very similar (ANCOVA, F beta equals 0.066, NS; F mu equals 3.657, p equals 0.01). The same result was obtained after controlling for years of education (ANCOVA, F beta equals 1.379, NS; F mu equals 5.191, p equals 0.002).
The EDS was applied at the time of onset of bladder incontinence in 60 cases (23 AD, 10 DLBD, 11 AD plus LB, and 16 AD plus VL), and the mean scores were significantly better in DLBD than in the other groups Table 2. To avoid the nonnormal distribution of the scores in AD cases, they were also categorized in three groups (score 0 to 40, 41 to 120, and more than 120), and the distribution of frequencies in a 3 times 4 Table wereanalyzed with the nonparametric chi2 test Table 2. This distribution was significantly different from random (chi2 20.430, df 6, p equals 0.002). Only nine AD cases (39%) but 10 DLBD cases (100%), nine AD plus LB cases (82%), and 10 AD plus VL cases (63%) scored in the EDS more than 0 at the time of onset of bladder incontinence. These findings cannot be attributed to behavioral or functional disturbances because the scores at this time in the LPRS were very similar in all groups Table 2.
Table 2. Cognitive and behavioral scores at the onset of bladder incontinence
The longitudinal scores in the EDS plotted against time before and after onset of bladder incontinence are presented in the Figure 1. It can be observed that they markedly fall in most AD patients when the incontinence begins, but this decline appears after several years in most DLBD patients. In the other groups, there is a similar but less definite delay in the cognitive decline after the onset of incontinence.
Figure 1. Evolution of cognitive decline and onset of urinary incontinence. The scores in the EDS markedly fall in most AD patients when the urinary incontinence begins. This decline appears after several years in most DLBD patients and with a less definite delay in the other groups. *Every line represents a case except in AD where it averages two cases with similar scores at the onset of incontinence.
These evolutive differences between groups do not appear when the stages of the Clinical Dementia Rating are used.
Discussion.
There are two possible limitations of our study. First, this sample of volunteers who joined the Dementia Study of the University of Western Ontario and underwent an autopsy is not representative of the total population of demented patients. However, most cases were included several years before the onset of incontinence and a selection bias is unlikely. Second, although the Dementia study was longitudinal and prospective, the urinary incontinence was not systematically stated in the clinical records. However, one item of the LPRS provided enough information about incontinence. The information was collected by a blinded reviewer without any bias from the clinical and pathologic diagnosis. Therefore, this study has been performed with most of the precautions applicable to clinicopathologic reviews.
Our results are in accordance with previous studies reporting that DLBD predominates in males [16] and that vascular lesions are more frequent with increasing age. [21] Most importantly, the patterns of urinary incontinence are different in every group of demented patients.
Previous clinical [7] and pathologic [22] studies have found frequent and early urinary incontinence in dementia of vascular origin, and there are reports of incontinence resulting from bilateral vascular lesions in the basal ganglia. [23] Moreover, one neuroimaging study [24] suggested that minor subcortical vascular lesions in AD are associated with urinary incontinence. However, in our series, incontinence onset is very similar in AD plus VL cases and in AD cases, perhaps because the vascular lesions were very mild in most of the former. The usefulness of early urinary incontinence as a marker of ``vascular dementia'' cannot be estimated in our series because all cases were primary degenerative dementias, but we believe it can have diagnostic value in differentiating DLBD from AD.
The onset of urinary incontinence in DLBD cases occurred shortly after the signs of cognitive impairment became evident. The abundance of LB inclusions in the midfrontal and cingular gyri in these cases [25] might produce early loss of bladder control. In several clinical studies, demented patients with extrapyramidal features, hallucinations, paranoid behavior, or delusions (four clinical markers of DLBD [16,25,26]) are more likely to have incontinence [27] and functional decline in basic activities of daily living. [28,29] In Parkinson's disease, there are frequent vesicosphincteric disorders (mainly detrusor hyperactivity, but also detrusor hypoactivity and delayed relaxation of the striated sphincter) and sometimes urinary incontinence. [30,31]
The onset of urinary incontinence was a relevant milestone in AD cases but not in the other dementing diseases. AD cases usually present severe cognitive impairment when they become incontinent, as distinct from the other groups, especially DLBD. This discrepancy may explain the contradictory results reported in the literature. Davidson et al. [6] found no differences in the neuropsychological performances of continent and incontinent demented patients diagnosed only on clinical grounds; however, incontinent patients were worse in the copy task performance, a cognitive function selectively impaired in DLBD, according to the study of Hensen et al. [26] On the other hand, Drachman et al. [32] observed in a group of probable AD that degree of cognitive impairment was a good predictor of subsequent incontinence.
In summary, loss of continence is associated with severe cognitive decline in AD but usually precedes mental failure in cases with cortical LB and perhaps when AD is associated with vascular lesions. Demented patients in general are best staged by methods such as the Clinical Dementia rating scale, but the onset of urinary incontinence is a very good objective milestone in the staging of cases with a firm diagnosis of AD.
Acknowledgments
We are indebted to many people who worked in the follow-up of patients included in the Dementia Study of the University of Western Ontario and in the collection of clinical reports. M. Eliaszew provided statistical advice.
Footnotes
-
.AB.-Incontinence is a hallmark of dementia, but little is known about its inception in different types of dementing diseases. We recorded the dates of onset of dementia and of urinary incontinence in 73 demented patients followed for 5.6 plus minus 2.5 years. The pathologic diagnosis was Alzheimer's disease (AD) in 29 cases, diffuse Lewy body disease (DLBD) in 11 cases, AD with Lewy bodies (AD plus LB) in 13 cases, and AD with vascular lesions (AD plus VL) in 20 cases. The onset of urinary incontinence was significantly earlier in DLBD cases (3.2 plus minus 1.4 years after dementia onset) than in AD (5.9 plus minus 2.5), AD plus LB (5.8 plus minus 2.4), and AD plus VL (6.5 plus minus 2.3) (p less than 0.01). At the onset of bladder incontinence, the mean score in the Extended Dementia Scale was significantly higher (i.e., cognition was better) in DLBD cases (109.3 plus minus 70.8) than in AD (21.3 plus minus 40.4), AD plus LB (45.6 plus minus 45.1), and AD plus VL (39.2 plus minus 54.9) cases (p less than 0.01). Urinary incontinence is associated with severe cognitive decline in pure AD but usually precedes severe mental failure in DLBD cases. This temporal pattern of cognitive decline and incontinence could be useful in differentiating these two dementing illnesses.| NEUROLOGY 1996;46:682-686
- Copyright 1996 by the Advanstar Communication Inc.
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