Comparing Cognitive Profiles of Niemann-Pick Disease Type C and Primary Dementia

The rare disease, Niemann-Pick disease type C (NP-C), is a progressive neurodegenerative disease caused by mutations in the NPC1 or the NPC2 gene. Although a disease-specific therapy is available, a recent study in Orphanet Journal of Rare Diseases aimed to distinguish clinically between the cognitive profiles in NP-C and primary dementia.

The study compared neurocognitive profiles of patients with confirmed NP-C and early Alzheimer disease (eAD). All patients in the study underwent neurocognitive assessment using dementia screening tests and other extensive tests that aimed to assess verbal memory, visuoconstructive abilities, visual memory, executive functions, and verbal fluency. According to the authors, cognitive impairment before the age of 65 is a characterization of early-onset cognitive decline, which is being increasingly reported. Most of those cases are related to eAD.

“However, compared to dementia in patients aged > 65 years, there is a much wider range of differential diagnoses, including underlying inherited neurodegenerative aetiologies such as NP-C,” explained the authors.

All of the study participants underwent follow-up visits for at least 12 months and their functional disability was evaluated in patients with NP-C using a disease-specific scale which assessed 6 key domains—ambulation, manipulation, language, swallowing, ocular movements, and epilepsy—on a scale of 0 (best) to 24.

The results showed that overall cognitive impairment was significantly higher in eAD versus NP-C. Also, the frequency of patients who were classified as cognitively impaired was greater in eAD versus NP-C.

Those with NP-C demonstrated relatively preserved verbal memory, but frequent impairment in visual memory, visuoconstruction, executive functions and specifically in verbal fluency. The eAD group demonstrated a wider profile of more frequent and more severe neurocognitive deficits, specifically featuring severe verbal and visual memory deficits with major executive impairment.

“Overall, taking patient age, gender, and education into account, eAD patients showed wider, more generalised impairments in affected cognitive domains compared with the profile seen in NP-C patients in the current study,” concluded the researchers. “Deficits were also more frequent and greater in magnitude in eAD on most of the neurocognitive tests that we employed.”

Based on the results, the researchers recommended that general dementia screening assessments should not be used alone to evaluate cognitive performance in patients with suspected NP-C since these patients may demonstrate milder cognitive deficits than eAD patients.

The researchers call for future studies with larger numbers of patients in order to gain further insight into the assessment of NP-C and other diseases.