In this prospective study of patients who underwent shunting for iNPH, we found a high prevalence of AD pathology, comparable to that previously reported in similarly aged patients.16
Overall, patients in our cohort who underwent shunting for iNPH experienced improvements in gait, cognition, and bladder control. However, patients with moderate-to-severe tau and Aβ pathology demonstrated more severe baseline impairment on a composite measure of cognition and poorer performance postoperatively on NPH symptom severity scales and measures of cognition. Finally, in sharp contrast to individuals with less severe pathology, patients with moderate-to-severe pathology failed to demonstrate benefit on any study measures assessing gait, cognition, and incontinence at 4-month follow-up.
These findings are noteworthy in the context of prior studies in which the presence of AD pathology did not affect outcomes among patients shunted for iNPH. For example, Bech and colleagues3
found AD pathology in 6 of 27 patients treated for iNPH, and interestingly noted a tendency toward a higher improvement rate in patients with AD pathology. Golomb and colleagues4
found that cortical AD pathology in patients with iNPH correlated with dementia severity and gait impairment at presentation, but not with subsequent outcomes. Bech-Azeddine and colleagues5
found pathologically diagnosed AD in 7 (25%) of 28 patients and determined that the presence of clinical features of AD did not accurately predict response to shunting, but did not specifically evaluate the impact of cortical pathology on clinical outcome.
Several factors may have contributed to differences between the current and prior findings. The methods used to measure AD pathology have varied between studies. Bech and colleagues3
did not employ tau as a pathologic criterion; Golomb and colleagues4
used neuritic plaques as the sole measure of pathology. These and other technical issues, including antibodies, antigen retrieval methods, and the timing of biopsy during the onset and progression of iNPH, may account for a higher incidence of AD pathology in our cohort than that observed in prior similar investigations.4,17
Moreover, our finding that patients with mild pathology respond well to shunting is consistent with data indicating that some patients are relatively unimpaired by the presence of cortical AD pathology,18
and suggests that prior studies that used dichotomous distinctions between patients with and without AD may have obscured the performance of patients with more severe AD pathology by grouping them with milder cases.
One limitation of the study is that CSF dynamics, an important consideration in the diagnosis of iNPH, was not formally assessed.11
However, there is no evidence to suggest that patients with or without AD pathology who present with clinical and radiographic features of iNPH would differ in this respect. Another limitation of this study is its relatively small sample size. If our data could be replicated in larger samples, they would suggest that measures of cortical tau and Aβ are potentially useful in predicting outcomes for patients being evaluated for iNPH. This is germane in the context of growing evidence that biological markers such as Aβ and tau derived from CSF may prove useful for signifying the presence of AD.19
Furthermore, techniques such as positron emission tomography imaging with 11
C-labeled Pittsburgh compound B—a compound retained in cortical regions that contain significant Aβ—also hold promise as tools for assessing the presence and progression of AD.20
Given our finding that cortical tau and Aβ accumulations are associated with poorer outcomes, noninvasive techniques that identify the presence of AD pathology may potentially play an important future role in the evaluation of iNPH.