Evaluation of coexistence of Alzheimer’s disease in idiopathic normal pressure hydrocephalus using ELISA analyses for CSF biomarkers
BMC Neurology
Evaluation of coexistence of Alzheimer's disease in idiopathic normal pressure hydrocephalus using ELISA analyses for CSF biomarkers
Tae Sung Lim 0
Jun Young Choi 0
Sun Ah Park 2
Young Chul Youn 1
Hyun Young Lee 3
Byung Gon Kim 0
In Soo Joo 0
Kyoon Huh 0
So Young Moon 0
0 Department of Neurology, School of Medicine, AjouUniversity , 5 San, Woncheon-dong, Yongtong-gu, Suwon-si, Kyunggi-do 442-749 , Republic of Korea
1 Department of Neurology, Chung-Ang University College of Medicine , Seoul , Republic of Korea
2 Department of Neurology, Soonchunhyang University College of Medicine , Bucheon , Republic of Korea
3 Regional Clinical Trial Center, Ajou University Medical Center , Suwon , Republic of Korea
Background: We investigated levels of the -amyloid 1-42 (A42), total tau protein (T-tau) and tau phosphorylated at position threonine 181 (P-tau) in cerebrospinal fluid (CSF) of idiopathic normal pressure hydrocephalus (iNPH) patients and tried to find their clinical implications in the evaluation and treatment of iNPH. Method: Twenty-five possible iNPH patients were prospectively enrolled and their CSF was collected to analyze levels of A42, T-tau and P-tau using ELISA method. Gait disturbance, urinary incontinence, and cognitive impairment were semi-quantified and detailed neuropsychological (NP) test was performed. Result: Eight iNPH patients were classified into the lower CSF A42 group and 17 patients were classified into the higher CSF A42 group. There was no difference in the iNPH grading score and its improvement after LP between the two groups. The lower CSF A42 group showed more deficits in attention, visuospatial function and verbal memory in the baseline NP test and less improvement in phonemic categorical naming and frontal inhibitory function after LP. Conclusions: Our study suggested that concomitant AD in iNPH patients might contribute to lumbar puncture or shunt unresponsiveness, especially in the field of cognitive dysfunction.
Normal pressure hydrocephalus; Alzheimer's disease; Cerebrospinal fluid; Lumbar puncture; Neuropsychological tests
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Background
Idiopathic normal pressure hydrocephalus (iNPH) is
characterized by a clinical triad of symptoms including
cognitive impairment, gait difficulty, and urinary incontinence
along with ventricular enlargement in brain imaging [1,2].
It is a potentially reversible cause of cognitive and motor
impairment in older adults using ventriculo-peritoneal
(VP) shunt or ventriculo-atrial (VA) shunt operation.
While treatment with VP shunts is widely used and
effective, the complication rate is high [3] and the risk factors
for shunt unresponsiveness are poorly understood. A
possible contributor to shunt unresponsiveness is the
presence of comorbid neurologic conditions that are
common in the aged, such as Alzheimers disease (AD) [4].
AD and iNPH have different pathomechanism, but
recent studies pointed out common pathomechanism
between the two diseases [5,6]. However there is still
controversy about the clinical implications of the
coexistence of AD pathology in iNPH patients. Some suggested
that AD was only a bystander and the rate of coexistence
of AD was similar to that of normal population [7-9] while
the others reported the poor shunt response was possibly
due to AD pathology [4,10]. Since the introduction of
ELISA method to detect cerebrospinal fluid (CSF)
biomarkers for AD, there have been many studies about the
differential role of levels of the -amyloid 142 (A42),
T-tau protein (T-tau) and tau phosphorylated at position
threonine 181 (P-tau) in CSF of iNPH patients [11-15].
However, there are still debates about the level of each
biomarker in two diseases and the implication of their
changes [16,17].
The aim of this study was to investigate levels of the
A42, T-tau and P-tau in CSF of iNPH patients and
describe the clinical implications in the evaluation and
treatment of iNPH.
Methods
Participants
Among patients who visited the Department of Neurology
at the Ajou Medical Center, Suwon, Korea from March
2010 to February 2012, we consecutively recruited 25
patients who satisfied the criteria for possible iNPH. All
patients had had brain MRIs and an LP. The clinical criteria
for possible iNPH included following: (1) MRI showing
ventricular enlargement (2) Any one symptom from
clinical triad (gait disturbance, cognitive deficit or urinary
disturbance) which was considered as a symptom compatible
with iNPH by the clinician [2]. After making a diagnosis
of iNPH, one or two LPs were performed to drain 30 to
50 ml of the CSF and 10 ml of CSF was collected to
evaluate biomarkers for AD. The diagnosis of iNPH was made
independently from the patients response to the LPs.
The CSF of 17 AD patients and 10 normal control
subjects which were collected and stored previously at two
other hospitals (S.C.H.U.H. and C.A.U.H.) was tested to
get a cutoff value of the coexistence of AD. All AD
patients met the criteria for probable AD as proposed (...truncated)