Hallmarks of dementia found well before diagnosis in one large family living in Colombia

Good news! Will we soon have regular checkups? 

However, this is a very specialized study focusing only on one large family living in one city located in Colombia. 

"A new study led by investigators at Massachusetts General Hospital shows that early accumulation of amyloid-β and tau protein begins to disrupt the brain’s connections important for memory years before signs of cognitive impairment were observed. ...

To learn more about this phenomenon, [researchers] used positron emission tomography (PET) for tau and amyloid-β, and functional magnetic resonance imaging (fMRI) to study how Alzheimer’s disease pathologies related to connectivity of brain regions and networks in individuals from a large family of more than 6,000 living members with Alzheimer’s disease prevalence from Antioquia, Colombia, South America.

Those who have the mutation known as Presenilin-1 E280A) are almost certain to develop Alzheimer’s disease dementia, usually showing signs of mild cognitive impairment (MCI) at age 44 and dementia by the age of 49. None of the individuals studied had any cognitive symptoms yet. ...
Previously, this research team showed that these individuals exhibit high levels of amyloid-β almost two decades before the onset of MCI, and tau pathology close to six years before onset. ...
The team used fMRI to examine regions of the brain at the voxel level, akin to pixels that represent 3D units encompassing millions of brain cells, to look at connectivity within and between different networks of the brain. They learned that mutation carriers displayed connection disruptions in the brain’s main memory network years before onset of cognitive impairment in the family. The researchers also developed a novel mathematical approach merging both fMRI and molecular imaging to see more clearly when brain regions begin to disconnect during the disease process. ..."

From the abstract:

"... We used high-resolution (voxel-level) graph-based network analyses to test whether in vivo amyloid-β and tau burden was associated with the segregation and integration of brain functional connections, and episodic memory, in cognitively unimpaired Presenilin-1 E280A carriers who are expected to develop early-onset AD dementia in ∼13 y on average. Compared to noncarriers, mutation carriers exhibited less functional segregation and integration in posterior default-mode network (DMN) regions, particularly the precuneus, and in the retrospenial cortex, which has been shown to link medial temporal regions and cortical regions of the DMN. Mutation carriers also showed greater functional segregation and integration in regions connected to the salience network, including the striatum and thalamus. Greater tau burden was associated with lower segregated and integrated functional connectivity of DMN regions, particularly the precuneus and medial prefrontal cortex. In turn, greater tau pathology was related to higher segregated and integrated functional connectivity in the retrospenial cortex and the anterior cingulate cortex, a hub of the salience network. These findings enlighten our understanding of how AD-related pathology distinctly alters the brain’s functional architecture in the preclinical stage, possibly contributing to pathology propagation and ultimately resulting in dementia."

Hallmarks of dementia found well before diagnosis – Harvard Gazette Accumulation of amyloid-β and tau proteins are related to brain network changes years before symptoms

Amyloid-β and tau pathologies relate to distinctive brain dysconnectomics in preclinical autosomal-dominant Alzheimer’s disease (no public access)