Reversible Alzheimer’s Disease: The role of normal-pressure hydrocephalus

Between 9 and 13 percent of residents in nursing homes and assisted living facilities are likely mis-diagnosed with Alzheimer’s disease and can be cured. Anthony Marmarou with the Virginia Commonwealth University Medical Center, Richmond, Virginia and his colleagues investigated how common it is to find buildup of fluid in the brain among clients in assisted-living and extended-care facilities. [1]  Known as idiopathic (unknown cause) normal-pressure hydrocephalus (iNPH), this condition mimics the behavior of Alzheimer’s disease. Normal-pressure hydrocephalus occurs when there is a restriction in the spaces that hold fluid deep inside the brain, resulting in pressure build-up. The pressure compresses the soft tissues of the brain restricting its function. The authors found that out of 147 patients between 9 to 14% had NPH depending on the diagnostic criteria used. Among these 17 patients, 11 received shunts and seven of these showed either transient or sustained improvement a year later. Although they were likely diagnosed with Alzheimer’s disease, a year later most were cured.

The symptoms of normal-pressure hydrocephalus are very similar to Alzheimer’s disease. When identified as a distinct disease it is known as the “wet, wild, and wobbly.”  Characterized by urinary incontinence (wet), dementia (wild), and gait dysfunction (wobbly). It is estimated that 1.6–5.4% of those with dementia are affected by iNPH.[2]  If the condition is left untreated—most of these cases are overlooked as Alzheimer’s disease—chronic iNPH patients share overlapping characteristics with Alzheimer’s disease in 75% of the time. It becomes increasingly difficult to differentiate the two the longer that iNPH is left untreated since the NPH syndrome will become Alzheimer’s disease.

Although there is no community-wide study looking at how common NPH is, there are some small sample studies that indicates that it is likely to be very common among older adults 65 years older. [3]  Among older adults in the community, the prevalence is around 1.3%, higher in assisted-living and extended-care residents with 11.6%. A small proportion of patients (2%) show permanent improvement after releasing the pressure in the brain using a shunt. The problem is that there are no easy indicators—including brain imaging—for distinguishing iNPH and Alzheimer’s disease. The images must still be interpreted with clinical features, blood measurements, CSF biomarker measurements, tap test, and CSF drainage results.

Because it is hard to diagnose, iNPH remains under recorded. Many studies report an association between hypertension, vascular disease and iNPH—with strokes and heart attacks being common precursors—so there is a need to look at any vascular disease as a precursor to Alzheimer’s. And the problem is that Alzheimer’s disease is so broad a category that most things that affect the brain and cause behavior changes are likely to be diagnosed Alzheimer’s disease even though it is likely not, such as amyloid deposition, CSF biomarker content, and presence of vasculature diseases. [4] A diagnosis of Alzheimer’s disease is a prescription for lost hope, whereas vascular disease is more likely to be amenable to therapy.

Vascular dementia—where the plaques and tangles are caused by a lack of blood flow in the brain (called cerebral perfusion)—is confused with Alzheimer’s disease most often because both share the same biomarkers and have the same expression. They look the same to the inexperienced clinician. Cerebrovascular disease among adults over 75 years of age is a common condition—36 percent overall, 25 percent for coronary, 58 percent hypertension, and 11 percent for stroke. [5]  It seems likely that because of these co-morbidities, vascular dementia contributes to, and is sometimes mis-diagnosed as Alzheimer’s disease. The silent issue is recognizing how frequently vascular disease promotes dementia.  Contemporary neuroscience still lacks a thorough understanding of exactly what contribution cerebrovascular disease makes to cognitive impairment. [6]

The answer is to move away from the practice of calling anything that disturbs cognition as Alzheimer’s disease.[7] Clinicians need a strategy, a roadmap to differentiate all these different type of diseases because they have different causes. Knowing the cause is the first step to formulating a cure. That is, if we are truly serious about finding a cure for Alzheimer’s disease.

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[1] Marmarou A, Young HF & Aygok GA (2007) Estimated incidence of normal-pressure hydrocephalus and shunt outcome in patients residing in assisted-living and extended-care facilities. Neurosurgical Focus, 22(4); 1-8.

[2] Gallia GL, Rigamonti D, Williams MA (2006) The diagnosis and treatment of idiopathic normal pressure hydrocephalus. Nat Clin Pract Neurol 2, 375-381.

[3] Martín-Láez, R., Caballero-Arzapalo, H., López-Menéndez, L. Á., Arango-Lasprilla, J. C., & Vázquez-Barquero, A. (2015). Epidemiology of Idiopathic Normal Pressure Hydrocephalus: A Systematic Review of the Literature.World neurosurgery, 84(6), 2002-2009.

[4] Di Ieva, A., Valli, M., & Cusimano, M. D. (2014). Distinguishing Alzheimer's disease from normal pressure hydrocephalus: a search for MRI biomarkers.Journal of Alzheimer's Disease, 38(2), 331-350.

[5] Schiller J.S., Lucas J.W. & Peregoy J.A. (2012.) Summary health statistics for U.S. adults:National Health Interview Survey, 2011. National Center for Health Statistics. Vital Health Stat, 10(256).

[6] Jellinger K.A. (2008). Morphologic diagnosis of 'vascular dementia' - a critical update. J Neurol Sci, 270: 1-12

[7] Garrett MD (2015) Politics of Anguish: How Alzheimer's disease became the malady of the 21st century. Createspace. USA

© USA Copyrighted 2016 Mario D. Garrett