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Amyloid burden, cortical thickness, and cognitive function in the Wisconsin Registry for Alzheimer's Prevention.

Doherty BM, Schultz SA, Oh JM, Koscik RL, Dowling NM, Barnhart TE, Murali D, Gallagher CL, Carlsson CM, Bendlin BB, LaRue A, Hermann BP, Rowley HA, Asthana S, Sager MA, Christian BT, Johnson SC, Okonkwo OC - Alzheimers Dement (Amst) (2015)

Bottom Line: The Aβ+ group exhibited significant thinning of the entorhinal cortex and accelerated age-associated thinning of the parahippocampal gyrus compared with the Aβ- group.The Aβ+ group also had numerically lower, but nonsignificant, test scores on all cognitive measures, and significantly faster age-associated cognitive decline on measures of Speed & Flexibility, Verbal Ability, and Visuospatial Ability.Our findings suggest that early Aβ aggregation is associated with deleterious changes in brain structure and cognitive function, even in midlife, and that the temporal lag between Aβ deposition and the inception of neurodegenerative/cognitive changes might be narrower than currently thought.

View Article: PubMed Central - PubMed

Affiliation: Geriatric Research Education and Clinical Center, William S. Middleton Memorial VA Hospital, Madison WI ; Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI.

ABSTRACT

There is a growing interest in understanding how amyloid-β (Aβ) accumulation in preclinical Alzheimer's disease relates to brain morphometric measures and cognition. Existing investigations in this area have been primarily conducted in older cognitively-normal (CN) individuals. Therefore, not much is known about the associations between Aβ burden, cortical thickness, and cognition in midlife. We examined this question in 109, CN, late-middle-aged adults (mean age=60.72±5.65 years) from the Wisconsin Registry for Alzheimer's Prevention. They underwent Pittsburgh Compound B (PiB) and anatomical magnetic resonance (MR) imaging, and a comprehensive cognitive exam. Blinded visual rating of the PiB scans was used to classify the participants as Aβ+ or Aβ-. Cortical thickness measurements were derived from the MR images. The Aβ+ group exhibited significant thinning of the entorhinal cortex and accelerated age-associated thinning of the parahippocampal gyrus compared with the Aβ- group. The Aβ+ group also had numerically lower, but nonsignificant, test scores on all cognitive measures, and significantly faster age-associated cognitive decline on measures of Speed & Flexibility, Verbal Ability, and Visuospatial Ability. Our findings suggest that early Aβ aggregation is associated with deleterious changes in brain structure and cognitive function, even in midlife, and that the temporal lag between Aβ deposition and the inception of neurodegenerative/cognitive changes might be narrower than currently thought.

No MeSH data available.


Related in: MedlinePlus

Amyloid beta (Aβ) burden accelerates age-related brain structural changes. The plots depict predicted values derived from the regression equation (circles), with the line of best linear fit overlaid. Red circles/line = Aβ+ group, blue circles/line = Aβ− group.
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fig2: Amyloid beta (Aβ) burden accelerates age-related brain structural changes. The plots depict predicted values derived from the regression equation (circles), with the line of best linear fit overlaid. Red circles/line = Aβ+ group, blue circles/line = Aβ− group.

Mentions: Our analyses of the impact of Aβ burden on age-related structural changes revealed a trend for the Aβ+ group to have more pronounced age-associated thinning of the parahippocampal gyrus compared with the Aβ− group (age*Aβ rating P =.059). Although none of the other ROIs were significant (age*Aβ rating Ps >.1), the beta coefficient for the age*Aβ rating term was negative in virtually all analyses, indicating a similar acceleration of age-associated thinning within the Aβ+ group. These findings are plotted in Fig. 2.


Amyloid burden, cortical thickness, and cognitive function in the Wisconsin Registry for Alzheimer's Prevention.

Doherty BM, Schultz SA, Oh JM, Koscik RL, Dowling NM, Barnhart TE, Murali D, Gallagher CL, Carlsson CM, Bendlin BB, LaRue A, Hermann BP, Rowley HA, Asthana S, Sager MA, Christian BT, Johnson SC, Okonkwo OC - Alzheimers Dement (Amst) (2015)

Amyloid beta (Aβ) burden accelerates age-related brain structural changes. The plots depict predicted values derived from the regression equation (circles), with the line of best linear fit overlaid. Red circles/line = Aβ+ group, blue circles/line = Aβ− group.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492165&req=5

fig2: Amyloid beta (Aβ) burden accelerates age-related brain structural changes. The plots depict predicted values derived from the regression equation (circles), with the line of best linear fit overlaid. Red circles/line = Aβ+ group, blue circles/line = Aβ− group.
Mentions: Our analyses of the impact of Aβ burden on age-related structural changes revealed a trend for the Aβ+ group to have more pronounced age-associated thinning of the parahippocampal gyrus compared with the Aβ− group (age*Aβ rating P =.059). Although none of the other ROIs were significant (age*Aβ rating Ps >.1), the beta coefficient for the age*Aβ rating term was negative in virtually all analyses, indicating a similar acceleration of age-associated thinning within the Aβ+ group. These findings are plotted in Fig. 2.

Bottom Line: The Aβ+ group exhibited significant thinning of the entorhinal cortex and accelerated age-associated thinning of the parahippocampal gyrus compared with the Aβ- group.The Aβ+ group also had numerically lower, but nonsignificant, test scores on all cognitive measures, and significantly faster age-associated cognitive decline on measures of Speed & Flexibility, Verbal Ability, and Visuospatial Ability.Our findings suggest that early Aβ aggregation is associated with deleterious changes in brain structure and cognitive function, even in midlife, and that the temporal lag between Aβ deposition and the inception of neurodegenerative/cognitive changes might be narrower than currently thought.

View Article: PubMed Central - PubMed

Affiliation: Geriatric Research Education and Clinical Center, William S. Middleton Memorial VA Hospital, Madison WI ; Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI.

ABSTRACT

There is a growing interest in understanding how amyloid-β (Aβ) accumulation in preclinical Alzheimer's disease relates to brain morphometric measures and cognition. Existing investigations in this area have been primarily conducted in older cognitively-normal (CN) individuals. Therefore, not much is known about the associations between Aβ burden, cortical thickness, and cognition in midlife. We examined this question in 109, CN, late-middle-aged adults (mean age=60.72±5.65 years) from the Wisconsin Registry for Alzheimer's Prevention. They underwent Pittsburgh Compound B (PiB) and anatomical magnetic resonance (MR) imaging, and a comprehensive cognitive exam. Blinded visual rating of the PiB scans was used to classify the participants as Aβ+ or Aβ-. Cortical thickness measurements were derived from the MR images. The Aβ+ group exhibited significant thinning of the entorhinal cortex and accelerated age-associated thinning of the parahippocampal gyrus compared with the Aβ- group. The Aβ+ group also had numerically lower, but nonsignificant, test scores on all cognitive measures, and significantly faster age-associated cognitive decline on measures of Speed & Flexibility, Verbal Ability, and Visuospatial Ability. Our findings suggest that early Aβ aggregation is associated with deleterious changes in brain structure and cognitive function, even in midlife, and that the temporal lag between Aβ deposition and the inception of neurodegenerative/cognitive changes might be narrower than currently thought.

No MeSH data available.


Related in: MedlinePlus