Alzheimer's Disease: Atrophy Pattern and Symptoms

Memory impairment is a key symptom of Alzheimer's dementia common to patients with the condition.

However, additional cognitive and behavioral symptoms vary between patients with a clinical and pathological diagnosis of Alzheimer's disease.

A key area of research is focused on understanding factors that contribute to symptom variability in Alzheimer's disease.

A team of researchers from Singapore and Harvard Medical School recently published an important study on this topic.

They analyzed structural MRI images from a group of 188 subjects in the Alzheimer's Disease Neuroimaging Initiative.

Using a mathematical model known as latent Dirichlet allocation they were able to identify three distinct areas of atrophy of variable severity in their cohort. These three factors were found to be:

• Temporal atrophy: temporal cortex, hippocampus and amygdala
• Cortical atrophy: frontal, parietal, lateral temporal and lateral occipital cortex regions
• Subcortical atrophy: striatum, thalamus and cerebellum

Individual patterns of atrophy within subjects were found to be stable over time. This means the atrophy patterns are not just a reflection of the stage of the Alzheimer's disease.

As expected, patterns of atrophy correlated with neuropsychological domains of impairment. Temporal atrophy subjects had the greatest memory impairment. Cortical atrophy patients showed the most impairment in executive function. Subcortical atrophy subjects had lower levels of executive function and memory impairment and showed a slower rate of cognitive decline.

Patients tended to fall into factor groups where more than one area of atrophy was noted, i.e. cortical and temporal atrophy but not subcortical atrophy.

The authors note their findings support the heterogeneity of Alzheimer's disease affecting different cognitive and behavioral features as well as variability in disease progression.

This is an important study in understanding the clinical manifestation of Alzheimer's disease. Readers with more interest in this research can access the free full-text manuscript by clicking on the link in the citation below.

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Brain image highlighting regions of the subcortex is an iPad screen shot from the app Brain Tutor.

Zhang X, Mormino EC, Sun N, Sperling RA, Sabuncu MR, Yeo BT, & Alzheimer’s Disease Neuroimaging Initiative. (2016). Bayesian model reveals latent atrophy factors with dissociable cognitive trajectories in Alzheimer's disease. Proceedings of the National Academy of Sciences of the United States of America PMID: 27702899

Brain Imaging and Conduct Disorder: Temporal Lobe Abnormalities

Conduct disorder is a complex behavioral disorder with significant risk for later adult psychopathology.

There is increasing evidence for a biological basis for conduct disorder.

Twin studies show a significant genetic contribution to the disorder.

Brain imaging studies also point to biological factors in conduct disorder.

Gregory Wallace and colleagues recently published a structural MRI study of conduct disorder in 22 adolescents between the ages of 10 and 18. Conduct disorder subjects were compared to a group of 27 age-matched controls on imaging measures.

This study focused on measures of brain cortex thickness, brain surface area and degree of brain folding or gyrus formation.

Conduct disorder was linked to the following brain structural abnormalities:

• Reduced cortical thickness in the superior temporal lobes
• Reduced gyrus formation in the ventromedial frontal cortex
• Reduced volume of the the amygdala and striatum (putamen and pallidum) 

The research group also found a negative correlation between superior temporal lobe thickness and psychometric measures of callousness/unemotional styles.

The mechanism for the temporal lobe to be involved in the symptoms of conduct disorder is unclear. Cortical thinning in this region has been found in adults with psychopathy. 

The authors note that amygdala/temporal lobe integration is necessary for stimulus-reinforcement learning. This integration may explain some of the deficits found in the current study.

This study will be important for continuing research in the genetics and pathophysiology involved in conduct disorder. Intervention strategies will need to address potential biological deficits contributing to the behavioral and learning problems in conduct disorder.

Readers with more interest in this research can access the free full-text manuscript by clicking on the PMID link in the citation below.

Image of brain with superior temporal lobe highlighted in green is an iPad screen shot from the Brain Tutor app.

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Wallace GL, White SF, Robustelli B, Sinclair S, Hwang S, Martin A, & Blair RJ (2014). Cortical and subcortical abnormalities in youths with conduct disorder and elevated callous-unemotional traits. Journal of the American Academy of Child and Adolescent Psychiatry, 53 (4), 456-650 PMID: 24655655

ADHD and Brain White Matter Deficits

Structural brain imaging studies in ADHD fail to find consistent differences from non-ADHD populations.

However, there is increasing evidence linking ADHD to changes in brain white matter function.

An example of these findings is a recent study from China examining white matter in children with ADHD.

ADHD is typically subgrouped into inattention (ADHD-I), hyperactivity ADHD-H or combined categories (ADHD-C). In the recent Chinese study, inattention and combined subgroups of children were compared to control children without ADHD.

Diffusion tensor imaging or DTI was utilized in this study. This imaging techniques allow study of white matter function in various brain regions. A variety of specific connectivy circuits have been identified. The brain white matter connects brain regions in circuits allowing coordinated processing, cognition and behavior.

Using DTI measures of white matter integrity and function are calculated. These parameters are known as fractional anisotropy, radial diffusivity and axial diffusivity. 

The key findings from the Chinese study included the following:

• ADHD-I children showed white matter abnormalities in the temporo-occipital circuits
• ADHD-C showed the temporo-occipital abnormalities found in ADHD-I but had additional white matter abnormalities in the frontal-subcortical and fronto-limbic circuit regions
• Deficits in the brain region known as the cuneus and precuneus correlated with inattention scores 

This study is one of the first to suggest distinct brain white matter regional abnormalities in two subtypes of ADHD. Although both subtypes showed abnormalities in the temporo-occipital circuits, ADHD-C alone showed abnormalities in circuits related to motor function.

These brain white matter differences in a group of children of mean age 9 years may represent developmental delays that improve over time. Many adolescents and adults with childhood ADHD symptoms show significant improvement in later stages of development. 

However, some adolescents and adults will have persistent ADHD symptoms. In the next post, I will summarize a brain imaging study of adults with ADHD.

Readers with more interest in this study can access the free full-text manuscript by clicking on the PMID link below.

Figure is a screen shot from the iPad app Brain Tutor. It shows the white matter circuit fibers connecting the temporal lobe and occipital lobe. Deficits in this circuitry were noted in both types of ADHD in the present study.

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Lei D, Ma J, Du X, Shen G, Jin X, & Gong Q (2014). Microstructural abnormalities in the combined and inattentive subtypes of attention deficit hyperactivity disorder: a diffusion tensor imaging study. Scientific reports, 4 PMID: 25363043