Neurology: Relationship between cerebrovascular and Alzheimer's disease biomarkers and cholinergic white matter impairment in cognitively impaired patients

Some pathological processes can lead to the degeneration of the
cholinergic system in aging.
Attempts to determine the contribution of amyloid, Tau and cerebrovascular biomarkers to cholinergic white matter (WM) impairment in people with cognitive impairment were published in
the journal Neurology.

The pathological effects of amyloid and tau were evaluated by the Aβ42/40 ratio of CSF and phosphorylated tau (p-tau) levels, while CSF Aβ38 levels
were measured.
Cerebrovascular pathology is assessed by automatic segmentation of WM lesions (WMLs) on MRI
.
WM projection of cholinergics (i.
e.
, neurons and external capsule pathways) is modeled
using an atlas based on diffusion tensor imaging data.
Gender and APOE ε4 carriers were also included as relevant variables
.

A total of 203 individuals without cognitive impairment (all 70 years old and 51% female)
from the H70 Gothenburg birth cohort study were included.
WM lesion burden was the most important factor leading to the degeneration of the two cholinergic pathways (increased mean squared error [IncMSE] = 98.
8% for the external capsule pathway and IncMSE for the cerebellar pathway = 93.
3%)
.
Levels of Aβ38 and p-tau also contribute to the degeneration of cholinergic WM, especially in the exocystic pathway (IncMSE=28.
4% and IncMSE=23.
4%)
.
The Aβ42/40 ratio did not significantly contribute to the model (IncMSE< 3.
0%)
.
APOE ε4 carriers showed poor integrity of the cerebellar pathway (IncMSE=21.
33%)
.
Women had poor external capsule pathway integrity (IncMSE=21.
55%), independent of amyloid status, and did not differ significantly when comparing amyloid-positive versus amyloid-negative female participants (T201=-1.
55; P=0.
123).

In summary, in the elderly without cognitive impairment, WMLs play a central role
in the degeneration of cholinergic pathways.
The findings highlight the importance of the burden of WM lesions in the elderly population, which
should be taken into account when developing prevention protocols for neurodegeneration and cognitive impairment.

References:

Association of Cerebrovascular and Alzheimer Disease Biomarkers With Cholinergic White Matter Degeneration in Cognitively Unimpaired Individuals.
Neurology Oct 2022, 99 (15) e1619-e1629; DOI: 10.
1212/WNL.
0000000000200930