Alzheimers Dementia: Alzheimer's Disease: Synaptic Density and Cognitive Function

For 30 years, synapse loss has been known as a major pathological correlator of cognitive impairment in Alzheimer's disease (AD)
.

However, this claim is based on the very small number of patients studied by autopsy or biopsy in limited brain regions, most of whom are in moderate to severe stages of disease

A subsequent clinicopathological investigation involving individuals with mild cognitive impairment (MCI) and focusing on the hippocampus demonstrated that the number of synapses in the dentate gyrus (outer molecular layer) correlates with cognitive performance before death, In a pooled sample, patients with advanced dementia and normal controls were included
.

However, these results were derived in part from the inclusion of cognitively normal (CN) and neuropathologically confirmed controls and thus may not apply to synaptic loss across the AD continuum

With the recent advent of synaptic positron emission tomography (PET) imaging, we have begun to assess synaptic alterations in vivo
.

Synaptophysin 2A (SV2A) is expressed in almost all synapses and is located in the synaptic sac at the presynaptic terminal

Recently, [11C]UCB-J was developed as a PET tracer for SV2A and advanced to human studies
.

Adam P.
Mecca et al at Yale University observed a broad reduction in SV2A binding in medial temporal and neocortical brain regions in early AD compared with CN participants
.

However, initial attempts to link synaptic density with cognitive performance using PET imaging have been hampered by the use of limited cognitive measures

From this, they used [11C]UCB-J PET and a broad neuropsychological test scale to investigate the relationship between synaptic density and cognitive performance in early AD
.

They investigated the relationship between synaptic density measured by [11C]UCB-J PET and neuropsychological test performance in 45 patients with early AD
.

Specifically, the study sample included 64 participants—45 AD patients (28 mild dementia patients, 17 MCI patients), and 19 CN patients

In patients with early AD, global synaptic density was significantly positively correlated with both global cognition and performance in five separate cognitive domains
.

Synapse density is a stronger predictor of cognitive performance than gray matter volume

The primary analysis investigated the relationship between overall synaptic density (DVR) in affected regions and overall cognition in the AD group
.

The multiple linear regression model with DVR as the predictor and global cognition as the outcome was significant (F[4, 40] = 6.

The multiple linear regression model with global PVC-DVR as predictor and global cognition as outcome was significant (F[4, 40] = 4.
93, P = 0.
003, R2 = 0.
33), and synaptic density was globally cognitive Significant predictors (β = 2.
16, η2 = 0.
23, P = 0.
001)

The multiple linear regression model with global PVC-DVR as predictor and global cognition as outcome is significant

The multiple linear regression model with GM volume as the predictor and global cognition as the outcome was significant (F[4, 40] = 3.
57, P = 0.
014, R2 = 0.
26)
.

Taken together, these results confirm that neuropathological studies have shown a clear association between synaptic density and cognitive performance, and suggest that this association extends into the early stages of AD
.

These results corroborate neuropathological studies showing a clear association between synaptic density and cognitive performance and suggest that this association extends into the early stages of AD
.

 

Original source:
Mecca AP, O'Dell RS, Sharp ES, et al.

Synaptic density and cognitive performance in Alzheimer's disease: A PET imaging study with [ 11 C]UCB‐J.
Alzheimer's & Dementia.
Published online February 17, 2022: alz.
12582.
doi:10.
1002/alz.
12582

Synaptic density and cognitive performance in Alzheimer's disease: A PET imaging study with [ 11 C]UCB‐J.
Alzheimer's & Dementia.
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