Brain MRI and CT morphology in healthy aging and Alzheimer's disease

Background: The brain atrophy in individual Alzheimer's disease (AD) patients includes not only specific atrophy from AD pathology, but also atrophy induced by normal aging and cerebral vascular diseases. Although medial temporal lobe atrophy (MTA) together with CSF biomarkers is suggested to be the most important diagnostic markers for AD, it may not be specific. The current method of choice to measure MTA has been volumetric measurement based on 3D magnetic resonance imaging (MRI), but this complicated method has not been implemented clinically. Female sex has been suggested to be a risk factor for AD. The left hippocampus may be more vulnerable in AD. Atrophy of hippocampus has also been found to emerge in healthy adults, along with increased age.

Purposes: To investigate whether simple Computerized Tomography (CT) linear measurements of brain could be of value in AD work-up; to create a normative database of hippocampus volume in our large population-based study and to examine if there is an acceleration of hippocampal atrophy in normal aging; to examine the hippocampal and entorhinal cortex volumes in relation to vascular risk factors.

Material and Methods: In the CT study (Papers 1&2), 59 controls, 162 pure AD, and 86 AD with minor cerebrovascular changes (CVC) between the ages of 52 and 94 years were recruited from the Malmö Alzheimer Study. Abeta42, T-tau and P-tau in CSF were examined. CT linear measurements were performed, which included temporal horn ratio and supersellar cistern ratio that reflect MTA. In the MRI study (Papers 3&4), 544 healthy non-demented subjects (aged 60-97 years) were recruited from the Swedish National study of Aging and Care in Kungsholmen (SNAC-K). Hippocampal formation and entorhinal cortex were manually delineated. Semi-automatic tools were used to access the volume of 3rd, lateral ventricle and intracranial volume (ICV). Vascular risk factors were collected.

Results: In CT study (Papers 1&2), temporal horn ratio and suprasellar cistern ratio were the atrophy factors that contributed most significantly to the diagnoses with correct AD classification of 90.2%. The correct classification of AD+CVC from controls increased from 79.5% (only CSF biomarkers) to 84.6% (combined CT measurements with CSF biomarkers). However, little was changed in the pure AD group. In the MRI study (Papers 3&4), The normalized volumes of hippocampus in males were smaller than that in females. The right hippocampus was larger than the left. The rate of aging atrophy trend (AAT) for the expansion of ventricles was larger than the estimated hippocampal shrinkage. The age point (72y) was shown to represent the time when the acceleration of AAT in hippocampus starts in normal aging. The score of vascular risk factors was significantly associated with reduced volumes of hippocampus and entorhinal cortex only among men.

Conclusions: CT linear measurements could be of value in work-up of AD patients. Combined with the CT measure of MTA, the specificity of CSF biomarkers can be increased, but only in AD+CVC. In a non-demented elderly population, the females were more vulnerable to hippocampal atrophy. An acceleration of hippocampal atrophy may emerge and start around 72 years of age. An increasing burden of vascular risk factors is associated with reduced volume of hippocampus and entorhinal cortex.

List of scientific papers

I. Zhang Y, Londos E, Minthon L, Wattmo C, Liu H, Aspelin P, Wahlund LO (2008). "Usefulness of computed tomography linear measurements in diagnosing Alzheimers disease." Acta Radiol 49(1): 91-7
https://pubmed.ncbi.nlm.nih.gov/18210318

II. Zhang Y, Londos E, Minthon L, Wattmo C, Blennow K, Liu HJ, Bronge L, Aspelin P, Wahlund LO (2009). "Medial temporal lobe atrophy increases the specificity of cerebrospinal fluid biomarkers in Alzheimer disease with minor cerebrovascular changes." Acta Radiol 50(6): 674-81
https://pubmed.ncbi.nlm.nih.gov/19455444

III. Zhang Y, Qiu C, Lindberg O, Bronge L, Aspelin P, Bäckman L, Fratiglioni L, Wahlund LO (2010). "Acceleration of hippocampal atrophy in a non-demented elderly population: the SNAC-K study." Int Psychogeriatr 22(1): 14-25. Epub 2009 Dec 4
https://pubmed.ncbi.nlm.nih.gov/19958567

IV. Qiu C, Zhang Y, Bronge L, Bäckman L, Fratiglioni L, Aspelin P, Wahlund LO (2010). "Cluster of vascular factors and hippocampal regional volumes among older adults: A population-based MRI study." (Manuscript)