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Peripheral nerve impairments in older adults were tied to a higher risk of subsequent dementia, a study of longitudinal data showed.

Combined sensory and motor impairments in the lower leg doubled the risk of subsequent dementia (HR 1.92, 95% CI 1.29-2.88) compared with people who had no leg impairments, reported Willa Brenowitz, PhD, MPH, of the University of California San Francisco (UCSF), and co-authors.

Sensory nerve impairments alone were associated with a 1.4 times higher dementia risk (HR 1.43, 95% CI 0.89-2.30), the researchers wrote in .

"This study is the first to show a connection between peripheral nerve function and central brain function, in this case with dementia," co-author Kristine Yaffe, MD, also of UCSF, told MedPage Today. "The connection could be due to shared genetics or pathways that affect both peripheral and central nervous system."

"For clinicians, this study suggests that older adults with peripheral neuropathy should be monitored more closely for dementia," Yaffe added. "And we need more work to untangle the mechanisms for this connection."

Slow walking speed and poor gait can predict dementia, and motor and sensory impairments have been linked with Alzheimer's disease, noted Melissa Shuman-Paretsky, MD, of the Icahn School of Medicine at Mount Sinai in New York City, and Gustavo Roman, MD, of Houston Methodist Hospital in Texas, in an .

"Although the mechanisms linking the peripheral nervous system to dementia are unclear, there are pathogenic factors that support the relationship," Shuman-Paretsky and Roman wrote.

"A typical pattern of peripheral neuropathy sensory loss (distal, bilateral, symmetrical) has been described in the elderly," they pointed out. "This pattern is thought to be due to loss of energy production in the cell bodies in the dorsal root ganglia as a result of metabolic, toxic, and neurodegenerative etiologies."

"Additionally, neurodegenerative proteins have been found in the dorsal root ganglia, suggesting that the same process that occurs in brain neurons in the central nervous system is also occurring in the peripheral nervous system," the editorialists observed.

Brenowitz and co-authors studied data on 2,174 people who were 70 to 79 years old and dementia-free when they enrolled in the National Institute on Aging's study. About half of participants were women, and 35% were Black.

Sensory nerve impairment was tested with monofilament (standard 10 g and light 1.4 g) and vibration threshold of the toe. Motor impairments of the lower leg were measured using compound motor action potential (CMAP) amplitude and nerve conduction velocity. Incident dementia was determined over the course of 11 years by medical records, cognitive scores, and medications.

Overall, 45% of participants could not detect monofilament 1.4 g, 9% could not detect monofilament 10 g, 6% could not feel vibration, 10% had low CMAP amplitude, and 24% had slow conduction velocity.

After adjusting for covariates, incident dementia was associated with vibration deficit (HR 1.73, 95% CI 1.24-2.40). A borderline association was seen in people who could not detect monofilament 10 g (HR 1.35, 95% CI 0.99-1.84). Estimates for monofilament 1.4 g, CMAP amplitude, and conduction velocity were elevated but not significant (P>0.05). There was no significant interaction by sex or race.

Dementia risk rose with increasing number of impairments: for three or more peripheral nerve impairments, the HR for incident dementia was 2.37 (95% CI 1.29-4.38).

In subgroup analyses, links between dementia and monofilament or conduction velocity impairments tended to be higher in people who had diabetes, low vitamin B12, or an APOE4 allele, though most were not significant.

These findings have important clinical implications, the editorialists noted. "Screening for dementia should include examination of lower extremity sensitivity using pin-prick and the traditional 128 Hz tuning fork, comparing proximal versus distal perception," they wrote. "Peripheral impairments may help identify individuals who are in the early stages of cognitive decline before dementia begins or progresses."

The study had several limitations, Brenowitz and colleagues acknowledged. Peripheral nerve function was measured only in one leg at only one time point. In addition, the researchers did not know whether peripheral nerve impairments were drug-induced; to partly mitigate this, they adjusted for cancer history since chemotherapy is a common cause of peripheral neuropathy.

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