AD and NPH are Not Mutually Exclusive
August 1, 2000 3 minutes read
AD and NPH are Not Mutually Exclusive
Abstract & Commentary
Source: Golomb J, et al. Alzheimer’s disease comorbidity in normal pressure hydrocephalus: Prevalence and shunt response. J Neurol Neurosurg Psychiatry 2000;68:778-781.
From among 117 patients who underwent shunt operation for clinically diagnosed normal pressure hydrocephalus (NPH), Golomb and colleagues selected 77 who demonstrated cognitive impairment on examination. Fifty-six of the NPH subjects and caregivers consented to excision a 5 by 2 mm cortical biopsy adjacent to the shunt penetration site. Biopsies were considered to be positive for Alzheimer’s disease (AD) if even one neuritic plaque was identified by Bielschowsky silver-stained section. Global deterioration scale (GDS) ratings were obtained on all subjects and included evaluation of gait, praxis, memory, language, and executive functions. Videotaped assessment was rated by two independent viewers. The battery was administered preoperatively and an average of 4.3 months postoperatively.
Neuritic plaques were found in 23 biopsies. Twelve subjects showed diffuse plaques and six showed neurofibrillary tangles. The density of neuritic plaques was rated sparse in 10 cases and moderate in 13. Using CERAD criteria, Golomb et al diagnosed definite AD in seven patients, probable AD in nine, and possible AD in seven. As a group, patients with AD neuropathology were more cognitively impaired and exhibited greater gait dysfunction. There were no differences in age, gender, or in parameters such as frequency of incontinence between those found to have AD pathology and those who did not.
Many patients improved significantly after shunting, whether or not they demonstrated AD pathology. A small improvement in cognition was recorded for the AD-negative group (Z score increase of 0.29; P < 0.01), whereas the corresponding measure in the AD-positive group did not reach statistical significance (Z score increase of 0.23; P < 0.06) but showed a trend toward improvement.
Golomb et al concluded that AD may be a contributing factor in the dementia exhibited by patients diagnosed with NPH, and that patients with and without AD pathology may exhibit comparable responses to shunt placement. They recommend that patients who are deemed good candidates for shunt placement on clinical and radiographic grounds should not be denied surgery because of the suspicion that they also suffer from AD.
Commentary
Regrettably, this article has serious faults. The incidence of shunt-related complications was not vigorously addressed. It is unclear whether the subset of patients who completed the testing accurately represented the entire cohort. The only hard data presented are based on a four-month evaluation of 37 of the original group of 56 patients providing biopsies. Furthermore, Golomb et al omit naming which statistical tests they applied to draw conclusions from such a small number of persons. The criteria used for diagnosing AD by tiny neocortical biopsy are particularly troubling, as Golomb et al admit. We have longitudinally evaluated one of the NPH patients who underwent shunt placement and biopsy at their site. Their records indicate that they were given a diagnosis of AD based on the biopsy results. The patient has shown no cognitive decline for 42 months since the shunt was placed. This speaks both to the success of the VP shunt placement in that case and the inherent dangers of making a diagnosis of AD based on a tiny cortical biopsy.
We concur that NPH patients should not be categorically denied the option of surgical treatment just because of possible, coexisting AD. Nevertheless, other factors such as the relative risks of neurosurgery and the long-term effects of shunting must be considered before shunt placement in AD patients. Most important, we need better means of identifying true NPH cases and predicting shunt responsiveness, whether or not coexisting AD is present. —norman r. relkin & fred plum
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