Deep brain stimulation of the nucleus basalis of Meynert

Deep brain stimulation of the nucleus basalis of Meynert

Deep brain stimulation of the nucleus basalis of Meynert (NBM DBS) has been proposed as a treatment option for Parkinson disease dementia.

Low-frequency NBM DBS was safely conducted in patients with Parkinson disease dementia; however, no improvements were observed in the primary cognitive outcomes. Further studies may be warranted to explore its potential to improve troublesome neuropsychiatric symptoms 1).


Nombela et al., from Hospital Clínico San CarlosToronto Western Hospital, reported a Parkinson’s disease (PD) patient diagnosed with mild cognitive impairment who underwent DBS surgery targeting the Globus pallidus internus (GPi; to treat motor symptoms) and the nucleus basalis of Meynert (NBM; to treat cognitive symptoms) using a single electrode per hemisphere.

Compared to baseline, 2-month follow-up after GPi stimulation was associated with motor improvements, whereas partial improvements in cognitive functions were observed 3 months after the addition of NBM stimulation to GPi stimulation.

This case explores an available alternative for complete DBS treatment in PD, stimulating 2 targets at different frequencies with a single electrode lead 2).


A global experience is emerging for the use of DBS for these conditions, targeting key nodes in the memory circuit, including the fornix and nucleus basalis of Meynert. Such work holds promise as a novel therapeutic approach for one of medicine’s most urgent priorities 3).

A unique feature in the course of both Alzheimer disease (AD) and Parkinson’s dementia (PDD) is basal forebrain degeneration including the latter’s cholinergic projections to the cortex. Neurostimulation of ascending basal forebrain projections of the Nucleus basalis of Meynert (NBM) may, therefore, represent a new strategy for enhancing the residual nucleus basalis output. The relevance of the cholinergic forebrain for brain plasticity has, for instance, been illustrated by the reshaping of auditory receptive fields during and after stimulation of the NBM in the adult brain 4).

Deep brain stimulation of the nucleus basalis of Meynert is thought to positively affect cognition and might counteract the deterioration of nutritional status and progressive weight loss observed in Alzheimer disease (AD).

A study aims to assess the nutritional status of patients with AD before receiving DBS of the nucleus basalis of Meynert and after 1 year, and to analyze potential associations between changes in cognition and nutritional status.

Nutritional status was assessed using a modified Mini Nutritional Assessment, bioelectrical impedance analysis, a completed 3-day food diary, and analysis of serum levels of vitamin B12 and folate.

With a normal body mass index (BMI) at baseline (mean 23.75 kg/m²) and after 1 year (mean 24.59 kg/m²), all but one patient gained body weight during the period of the pilot study (mean 2.38 kg, 3.81% of body weight). This was reflected in a mainly stable or improved body composition, assessed by bioelectrical impedance analysis, in five of the six patients. Mean energy intake increased from 1534 kcal/day (min 1037, max 2370) at baseline to 1736 kcal/day (min 1010, max 2663) after 1 year, leading to the improved fulfillment of energy needs in four patients. The only nutritional factors that were associated with changes in cognition were vitamin B12 level at baseline (Spearman’s rho = 0.943, p = 0.005) and changes in vitamin B12 level (Spearman’s rho = -0.829, p = 0.042).

Patients with AD that received DBS of the nucleus basalis of Meynert demonstrated a mainly stable nutritional status within a 1-year period. Whether DBS is causative regarding these observations must be investigated in additional studies 5).

Case series

Case reports

References

1)

Gratwicke J, Zrinzo L, Kahan J, Peters A, Beigi M, Akram H, Hyam J, Oswal A, Day B, Mancini L, Thornton J, Yousry T, Limousin P, Hariz M, Jahanshahi M, Foltynie T. Bilateral Deep Brain Stimulation of the Nucleus Basalis of Meynert for Parkinson Disease Dementia: A Randomized Clinical Trial. JAMA Neurol. 2018 Feb 1;75(2):169-178. doi: 10.1001/jamaneurol.2017.3762. PubMed PMID: 29255885; PubMed Central PMCID: PMC5838617.
2)

Nombela C, Lozano A, Villanueva C, Barcia JA. Simultaneous Stimulation of the Globus Pallidus Interna and the Nucleus Basalis of Meynert in the Parkinson-Dementia Syndrome. Dement Geriatr Cogn Disord. 2019 Jan 10;47(1-2):19-28. doi: 10.1159/000493094. [Epub ahead of print] PubMed PMID: 30630160.
3)

Sankar T, Lipsman N, Lozano AM. Deep brain stimulation for disorders of memory and cognition. Neurotherapeutics. 2014 Jul;11(3):527-34. doi: 10.1007/s13311-014-0275-0. Review. PubMed PMID: 24777384; PubMed Central PMCID: PMC4121440.
4)

Kilgard MP, Merzenich MM. Cortical map reorganization enabled by nucleus basalis activity. Science (1998) 279(5357):1714–810.1126/science.279.5357.1714
5)

Noreik M, Kuhn J, Hardenacke K, Lenartz D, Bauer A, Bührle CP, Häussermann P, Hellmich M, Klosterkötter J, Wiltfang J, Maarouf M, Freund HJ, Visser-Vandewalle V, Sturm V, Schulz RJ. Changes in Nutritional Status after Deep Brain Stimulation of the Nucleus Basalis of Meynert in Alzheimer’s Disease – Results of a Phase I Study. J Nutr Health Aging. 2015;19(8):812-8. doi: 10.1007/s12603-015-0496-x. PubMed PMID: 26412285.

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