Concurrent Alzheimer’s pathology in patients with clinical normal pressure hydrocephalus: correlation of high-volume lumbar puncture results, cortical brain biopsies, and outcomes

Abstract

abbreviatioNs AD = Alzheimer's disease; CERAD = Consortium to Establish a Registry for Alzheimer's Disease; CSF = cerebrospinal fluid; GDS = Global Deterioration Scale; HVLP = high-volume lumbar puncture; NPH = normal pressure hydrocephalus. obJective Normal pressure hydrocephalus (NPH) remains most often a clinical diagnosis and has been widely considered responsive to the placement of a cerebrospinal fluid (CSF) shunt. The high incidence of patients with Alzheimer's disease (AD) with NPH symptoms leads to poorer outcomes than would be expected in patients with NPH alone. This article reviews a series of patients operated on for presumed NPH in whom preoperative high-volume lumbar puncture (HVLP) and intraoperative cortical brain biopsies were performed. The data derived from these procedures were then used to understand the incidence of AD in patients presenting with NPH symptoms and to analyze the efficacy of HVLP in patients with NPH and patients with concurrent AD (NPH+AD). A review of the outcomes of shunt surgery is provided. methods The cases of all patients who underwent placement of a CSF shunt for NPH from 1998 to 2013 at the University of Virginia by the senior author were retrospectively reviewed. Patients who underwent HVLP and patients who underwent cortical brain biopsies were stratified based on the biopsy results into an NPH-only group and an NPH+AD group. The HVLP results and outcomes were then compared in these 2 groups. results From 1998 to 2013, 142 patients underwent shunt operations because of a preoperative clinical diagnosis of NPH. Of the patients with a shunt who had a diagnosis of NPH, 105 (74%) received HVLPs. Of 142 shunt-treated patients with NPH, 27 (19%) were determined to have concomitant Alzheimer's pathology based on histopathological findings at the time of shunting. Patients who underwent repeat biopsies had an initial positive outcome. After they clinically deteriorated, they underwent repeat biopsies during shunt interrogation, and 13% of the repeat biopsies demonstrated Alzheimer's pathology. Improvements in gait and cognition did not reach significance between the NPH and NPH+AD groups. In total, 105 patients underwent HVLP before shunt placement. In the NPH cohort, 44.6% of patients experienced improvement in symptoms with HVLP and went on to experience resolution or improvement. In the NPH+AD cohort, this proportion was lower (18.2%), and the majority of patients who experienced symptomatic relief with HVLP actually went on to experience either no change or worsening of symptoms (p = 0.0136). coNclusioNs A high prevalence of AD histopathological findings (19%) occurred in patients treated with shunts for NPH based on cortical brain biopsies performed during placement of CSF shunts. HVLP results alone were not predictive of clinical outcome. However, cortical brain biopsy results and the presence of Alzheimer's pathology had a strong correlation with success after CSF shunting. Thirteen percent of patients who initially had a normal cortical brain biopsy result had evi...

Alzheimer Disease

“…Another example is that of a patient being considered for ventriculoperitoneal shunting for suspected normal pressure hydrocephalus. AD is the most frequent reason for therapeutic failure 127 so a biomarker test indicating the presence of AD pathology may help avoid unnecessary surgery. Whether or not an older patient with clinically probable AD should also undergo biomarker testing to further enhance diagnostic confidence is less clear.…”

Health‐related quality‐of‐life outcome in patients with idiopathic normal‐pressure hydrocephalus – a 1‐year follow‐up study

“…In our study, the absence of Ab or HPs pathology in the frontal cortical biopsy predicted the HRQoL outcome 1 year after the shunting (Fig. S1), which is logical, as the neurodegenerative comorbidities [7][8][9][10] and patients' old age [6,7] are associated with poorer outcome (Fig. S2, Table S3).…”

Diffusion Tensor Imaging of the Superior Thalamic Radiation and Cerebrospinal Fluid Distribution in Idiopathic Normal Pressure Hydrocephalus

“…Other neurodegenerative diseases, such as Alzheimer's, vascular dementia, and Parkinson's diseases, are also common in the same age population. Studies have shown coexistence of increased rate of Alzheimer's disease (AD) histopathology in patients with iNPH beyond what can be accounted for by chance alone . Studies have shown decrease CSF production and turnover in both AD and NPH .…”

“…Studies have shown coexistence of increased rate of Alzheimer's disease (AD) histopathology in patients with iNPH beyond what can be accounted for by chance alone. 6,7 Studies have shown decrease CSF production and turnover in both AD and NPH. 8 It was postulated by Silverberg that failure of CSF production or increased CSF flow resistance might lead to either AD, iNPH, or AD-NPH depending on which pathological process predominates.…”