Alzheimer’s & Brain Awareness Month: Why Are We Still Missing NPH?

The Scale of the Diagnostic Gap

NPH accounts for up to 5% of all dementia cases – a meaningful proportion in any memory or falls clinic. Nearly 800,000 older Americans may be living with NPH, yet over 80% of cases remain unrecognized or untreated. Fewer than 20% receive a correct diagnosis.

These are not figures that reflect a rare or poorly understood condition. They reflect a failure at the point of differential diagnosis.

Where the Differential Breaks Down

The overlap between NPH and Alzheimer’s disease is well-documented, and it runs deeper than symptom similarity alone. NPH remains a challenging clinical entity with significant overlap in presentation with other neurodegenerative disorders including Alzheimer’s disease, vascular dementia, and parkinsonian syndromes, especially progressive supranuclear palsy and dementia with Lewy bodies. 

Several factors compound the challenge:

• Cognitive profile overlap. NPH-related cognitive impairment – predominantly executive dysfunction, psychomotor slowing, and attentional deficits – can be difficult to distinguish from early Alzheimer’s on brief bedside assessment. Language and episodic memory are relatively spared in NPH, but this distinction is easily missed without structured neuropsychological evaluation.

• Gait assessment is inconsistently applied. Gait tends to be affected first and more severely than other domains in idiopathic NPH – making it the most discriminating early feature in the differential. Yet in practice, gait is rarely assessed quantitatively in memory clinic settings, and a shuffling, broad-based gait in an older patient is too often attributed to musculoskeletal causes or general deconditioning.

• Imaging findings are unreliable in isolation. Ventriculomegaly on CT or MRI raises suspicion, but cannot distinguish NPH from cerebral atrophy without functional CSF data. The DESH pattern (disproportionately enlarged subarachnoid space hydrocephalus) is supportive but not definitive.

• Comorbidity muddies the picture. The incidence of Alzheimer’s disease in patients with NPH is greater than in the general population, meaning the two conditions genuinely co-exist in a meaningful subset of patients – making clean differentiation harder, but no less important. A concurrent Alzheimer’s pathology does not preclude NPH treatment benefit; it makes accurate identification of the NPH component more, not less, critical.

Unlike Alzheimer’s, NPH Symptoms Can Be Treated

The PENS Trial – published in the New England Journal of Medicine in 2025 – provides the strongest evidence to date that shunting in correctly identified NPH patients produces clinically meaningful, durable outcomes.

Every participant had already demonstrated CSF-responsiveness via a drainage test prior to randomisation. The PENS Trial was not testing shunting in unselected suspected NPH – it was testing it in patients who had been correctly identified through functional CSF assessment. But, critically, the treatment effect is inseparable from the quality of patient selection upstream.

CSF Infusion Testing as the Differentiating Step

For patients where clinical and imaging findings are ambiguous – which, in the NPH/Alzheimer’s differential, is the majority – objective measurement of CSF outflow resistance (Rout) provides the functional data that resolves uncertainty. Elevated Rout is not present in Alzheimer’s disease or most other neurodegenerative conditions; it is a marker of impaired CSF absorption specific to the NPH pathophysiology.

XP One will bring standardized CSF infusion testing to the bedside: a 20-minute outpatient procedure, auto-calibrated for any lumbar puncture needle, delivering real-time Rout data. The goal is to remove the access and workflow barriers that currently keep most NPH patients from reaching the diagnostic step on which everything else depends.

Reach us at contact@x-pressure.com or visit our Solutions page to learn how XP One can support your NPH diagnostic pathway.