Age-associated differences are detected in the MTL with an acceleration of Medial Temporal Lobe Atrophy (MTA) starting around 72 years of age in healthy people (read more). However, these changes are modest and their rate of progression over time is relatively slow with a mean rate of about 1.6% per year. Accelerated MTA is a consistent finding in AD and MCI with rates of about 2.8% in stable MCI, 3.7% in MCI transitioning to AD (MCI progressors), and up to 4.0% in AD. Frontotemporal dementia may also lead to MTA, but in a different pattern: frontotemporal dementia and semantic dementia show atrophy in the anterior portion of the hippocampus, and in semantic dementia the atrophy is asymmetrical, with the left hippocampus being affected more severely. No significant hippocampal atrophy is detected in non-fluent progressive aphasia. Other diseases such as dementia with Lewy bodies do not show MTA or it is much milder.
In contrast to MTA, ventricular enlargement (body of lateral ventricles) in old people lacks specificity, representing a measure of global brain atrophy due to aging or any neurodegenerative disorder. Ventricular enlargement correlates with decline in cognitive performance and with cerebrospinal fluid pathologic markers of AD and several studied have assessed different methods based on the lateral ventricles measurements as AD biomarkers. However, it is well known that ventricular enlargement is a measure of global brain atrophy and is strongly associated with aging both in healthy and diseased people. In addition, almost any neurodegenerative disorder affecting the brain hemispheres leads to some degree of ventricular enlargement, including Parkinson’s disease, Frontotemporal Dementia, Lewy-Bodies Dementia and Corticobasal Degeneration and so do some psychiatric conditions. Thus, it is interesting to compare measures indicative of atrophy in the MTL with measures indicative of global brain atrophy. I propose the next indices, that allow us to interpret result of atrophy measures easier:
Planimetry methods consist in measuring the area of regions of interest (ROI). The areas of several ROI can be compared using ratios and indices. The Medial Temporal-Lobe Atrophy index (MTAi), is a simple method for measuring the relative extent of atrophy in the MTL in relation to the global brain atrophy. This 2D-method consists on calculating a ratio using the area of 3 regions traced manually on one single coronal MRI slide at the level of the interpeduncular fossa: 1. the medial temporal lobe region (A); 2. the parenchyma within the medial temporal region, that includes the hippocampus and the parahippocampal gyrus -the fimbria taenia and plexus choroideus were excluded- (B); and 3. the body of the ipsilateral lateral ventricle (C). Therefrom we can compute the “2D-Medial Temporal Atrophy” (2D-MTA=A-B) that represents absolute atrophy of the MTL; and the ratio “Medial Temporal Atrophy index” (MTAi = (A-B) x10 / C) that represents relative atrophy of the MTL. The MTAi is suitable to assess the asymmetry of relative MTA within a subject. High asymmetry is typical of some types of FTLD. However, as there is important interindividual variability in the size of the lateral ventricles, this index is not recommended for comparing subjects but to track the progression in a given subject over time. Indeed, if we have 2 MRI studies from different times (1= first one, 2=second one), we can also compute the yearly rate of MTA (yrMTA) as follows: yrMTA=(A2-B2)-(A1-B1) x 1200 / (#months between MRI studies) and the yearly rate of relative MTA (yrRMTA) as follows: yrRMTA=(A2-B2)-(A1-B1) x 1200 / (C2-C1) x (#months between MRI studies). High values are suggestive of "disproportionated" MTA in relation to the extent of global brain atrophy, and therefore the pattern of atrophy matches the expected in typical AD.
Volumetric methods are more sophisticated. The Medial Temporal-Lobe ratio (MTLr) compares the volume of the MTL with the whole hemispheric volume. To find out the MTLr we need 1. the volume of the hippocampus (A); the volume of the parahippocampal gyrus (B); 3. the volume of the whole brain hemisphere (C). We can compute the ratio “Medial Temporal Lobe ratio” as follows: MTLr = (A+B)^2 / C. Low values are suggestive of MTL atrophy, and therefore the pattern of atrophy matches the expected in typical AD.
If we have 2 MRI studies from different times (1= first one, 2=second one), we can also compute the yearly rate of MTL atrophy (yrMTL) =(A1+B1)-(A2+B2) x 1200 / (#months between MRI studies) and the yearly rate of relative MTL atrophy as follows: (yrMTLr) =(A1+B1)-(A2+B2) x 1200 / (C2-C1) x (#months between MRI studies).
The Hippocampus ratio (Hr) compares the volume of the hippocampus with the whole hemispheric volume. To find out the HAr we need 1. the volume of the hippocampus (A); 2. the volume of the ipsilateral brain hemisphere (B). We can compute the ratio “Hippocampus ratio” as follows: HAr= A^2 / B. Low values are suggestive of hippocampus atrophy, and therefore the pattern of atrophy matches the expected in typical AD.
If we have 2 MRI studies from different times (1= first one, 2=second one), we can also compute the yearly rate of Hippocampus Atrophy as follows: (yrHA)= (A1-A2) x 1200 / (#months between MRI studies) and the yearly rate of relative Hippocampus atrophy as follows: (yrHAr)=(A1-A2) x 1200 / (B1-B2) x (#months between MRI studies).
The Hippocampus-Ventricle index (HVi) is the addition of the volume of the hippocampus plus the tenth part of the volume of the the lateral ventricle. Then, to find out the HVi we need 1. the normalized volume of the hippocampus (A); 2. the normalized volume of the the lateral ventricle (B). We can compute the ratio “Hippocampus-Ventricle index” as follows: HVi = A+(B/10). Low HVi values are suggestive of AD pathology in incipient stages, while high HVi values are suggestive of global brain atrophy due to aging or any neurodegenerative disease other than AD. Intermediate values are not informative.
Volumetric indices for comparing the extent/rate of atrophy in the medial temporal lobe with the extent/rate of global brain atrophy (full text).
In PNFA there is often asymmetrical atrophy (though this can be subtle initially), predominantly affecting the left hemisphere and especially the inferior frontal lobe and/or anterior insula. With increasing disease progression there is involvement of left superior temporal, middle and superior frontal and anterior parietal lobes. There is also involvement of the caudate, and the right hemisphere. Some small studies suggest there may be different patterns of atrophy in PNFA patients with PSP compared to those without PSP, and also in those with progranulin mutations (FTLD-TDP pathologically) compared to those without. Progranulin mutations tend to be associated with very asymmetrical atrophy more widely affecting the frontal, temporal and parietal lobes.
Patients with logopenic aphasia have more posterior cortical atrophy than patients with PNFA, with left posterior temporal and parietal atrophy as well as hippocampal and posterior cingulate involvement, consistent with the high frequency of Alzheimer's pathology in this group.
Patients with SD characteristically have asymmetrical temporal lobe atrophy, usually more marked in the left hemisphere. It chiefly affects the anterior and inferior temporal lobe (also including the amygdala and hippocampus) with relative sparing of the superior temporal gyrus but striking atrophy of the pole with an antero-posterior gradient within the temporal lobe. As the disease progresses, areas within the left hemisphere outside the temporal lobe are involved, namely orbitofrontal, inferior frontal, insular, and anterior cingulate cortices, together with increasing atrophy of the right temporal lobe. This spread contributes to the behavioural changes in later SD. A 'mirror' pattern of initial atrophy and disease progression is seen in those patients presenting with right greater than left temporal lobe involvement. Although SD is characteristically FTLD-TDP pathologically, in small numbers of cases, Pick's disease (FTLD-tau) and occasionally Alzheimer's disease pathology are seen. There is a qualitatively different pattern in those with Alzheimer's disease with mostly hippocampal involvement, lack of the knife-edge anterior temporal atrophy seen in the other groups and without the sparing of the superior temporal gyrus. Other pathologies may have more posterior extension of atrophy.
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| Compares | Parameters needed to calculate it | Computing | Interpretation | |
| Temporal horn index (Ti) | Volume of the temporal horn with the volume of the lateral ventricles | Temporal horn volume (A) and the lateral ventricular volume (B) | THi= A / B | Low values are suggestive of MTL atrophy, and therefore the pattern of atrophy matches the pattern expected in typical AD |
| Medial Temporal-Lobe ratio (MTLr) | Volume of the MTL with the ipsilateral hemispheric volume | The volume of the hippocampus (A); the volume of the parahippocampal gyrus (B); the volume of the whole brain hemisphere (C) | MTLr = (A+B)2 / C | Low values are suggestive of MTL atrophy, and therefore the pattern of atrophy matches the pattern expected in typical AD |
| Yearly rate of MTL atrophy (yrMTLA) | Not an index | A and B as in MTLr in 2 different MRI studies | (yrMTL) = (A1+B1) - (A2+B2) × 1200 / (# mo between MRI studies) | High values are expected in typical AD |
| Yearly rate of relative MTL atrophy (yrRMTLA) | Rate of atrophy of the MTL with the rate of enlargement of the ipsilateral lateral ventricles | A, B and C as in MTLr in 2 different MRI studies | yrRMTA = (A1+B1)-(A2+B2) × 1200 / (C2-C1) × (# mo between MRI studies) | High values are expected in early typical AD |
| Hippocampus ratio (Hr) | Volume of the hippocampus with the ipsilateral hemispheric volume | The volume of the hippocampus (A); the volume of the ipsilateral brain hemisphere (B) | Hr = A2 / B | Low values are suggestive of hippocampus atrophy, and therefore the pattern of atrophy matches the pattern expected in typical AD |
| Yearly rate of Hippocampus Atrophy (yrHA) | Not an index | A as in Hr in 2 different MRI studies | (yrHA) = (A1-A2) × 1200 / (# mo between MRI studies) | High values are expected in typical AD |
| Yearly rate of relative Hippocampus Atrophy (yrRHA) | Rate of atrophy of the hippocampus with the rate of atrophy of the ipsilateral hemisphere | A and B as in Hr in 2 different MRI studies | yrRHA = (A1-A2) × 1200 / (B1-B2) × (# mo between MRI studies) | High values are expected in early typical AD |
| Hippocampus-Ventricle index (HVi) | Addition of the volume of the hippocampus plus the 10th part of the volume of the lateral ventricle | Normalized volume of the hippocampus (A); normalized volume of the lateral ventricle (B) | HVi = A + (B/10) | Low HVi values are suggestive of AD pathology in incipient stages; high HVi values are suggestive of global brain atrophy due to aging or any neurodegenerative disease other than AD |
In PNFA there is often asymmetrical atrophy (though this can be subtle initially), predominantly affecting the left hemisphere and especially the inferior frontal lobe and/or anterior insula. With increasing disease progression there is involvement of left superior temporal, middle and superior frontal and anterior parietal lobes. There is also involvement of the caudate, and the right hemisphere. Some small studies suggest there may be different patterns of atrophy in PNFA patients with PSP compared to those without PSP, and also in those with progranulin mutations (FTLD-TDP pathologically) compared to those without. Progranulin mutations tend to be associated with very asymmetrical atrophy more widely affecting the frontal, temporal and parietal lobes.
Patients with logopenic aphasia have more posterior cortical atrophy than patients with PNFA, with left posterior temporal and parietal atrophy as well as hippocampal and posterior cingulate involvement, consistent with the high frequency of Alzheimer's pathology in this group.
Patients with SD characteristically have asymmetrical temporal lobe atrophy, usually more marked in the left hemisphere. It chiefly affects the anterior and inferior temporal lobe (also including the amygdala and hippocampus) with relative sparing of the superior temporal gyrus but striking atrophy of the pole with an antero-posterior gradient within the temporal lobe. As the disease progresses, areas within the left hemisphere outside the temporal lobe are involved, namely orbitofrontal, inferior frontal, insular, and anterior cingulate cortices, together with increasing atrophy of the right temporal lobe. This spread contributes to the behavioural changes in later SD. A 'mirror' pattern of initial atrophy and disease progression is seen in those patients presenting with right greater than left temporal lobe involvement. Although SD is characteristically FTLD-TDP pathologically, in small numbers of cases, Pick's disease (FTLD-tau) and occasionally Alzheimer's disease pathology are seen. There is a qualitatively different pattern in those with Alzheimer's disease with mostly hippocampal involvement, lack of the knife-edge anterior temporal atrophy seen in the other groups and without the sparing of the superior temporal gyrus. Other pathologies may have more posterior extension of atrophy.
More info:
These indices make sense. AD patients show ventricular enlargement, but in early stages it is in a much lesser extent than the MTL atrophy. In addition, ventricular enlargement is such an unspecific feature that might be due to many conditions from normal aging to almost any neurodegenerative disorder. Therefore ventricular enlargement is a measure of unspecific global brain atrophy. On the other hand, MTA is much more specific of AD. This fact is crucial for the differential diagnosis of AD against other neurodegenerative disorders
ReplyDeleteGreat job!
ReplyDeleteVisual assessment is very quick, but not objective and can be affected by several variables. It is not suitable to monitorize the disease.
In my experience the MTAi is fast (about 5 minutes), objective, reproducible, and therefore suitable to monitorize the disease.
Age-related brain atrophy
ReplyDeleteCortical reductions in the healthy elderly were extensive after only 1 year, especially evident in temporal and prefrontal cortices, where annual decline was ∼0.5%. All subcortical and ventricular regions except caudate nucleus and the fourth ventricle changed significantly over 1 year (Fjell et al., 2009).
atrophy was found to accelerate with increasing age, and this was especially prominent in areas vulnerable to AD. Thus, it is possible that the accelerating atrophy with increasing age is due to preclinical AD (Fjell et al., 2009). shrinkage in the hippocampus and the cerebellum accelerated with age (Raz)
Gender may affect the rate of age-related atrophy in certain brain structures (Xu et al., 2000). As expected, rates of atrophy also differ across different neurodegenerative disorders (Whitwell et al., 2011)