Surgery and brain atrophy in cognitively normal elderly subjects and subjects diagnosed with mild cognitive impairment

Abstract

Background: Structural magnetic resonance imaging is used to longitudinally monitor the progression of Alzheimer disease from its presymptomatic to symptomatic phases. Using magnetic resonance imaging data from the Alzheimer's Disease Neuroimaging Initiative, we tested the hypothesis that surgery would impact brain parameters associated with progression of dementia.

Methods: Brain images from the neuroimaging initiative database were used to study normal volunteer subjects and patients with mild cognitive impairment for the age group 55 to 90 inclusive. We compared changes in regional brain anatomy for three visits that defined two intervisit intervals for a surgical cohort (n = 41) and a propensity matched nonsurgical control cohort (n = 123). The first interval for the surgical cohort contained the surgical date. Regional brain volumes were determined with Freesurfer and quantitatively described with J-image software (University of California at San Francisco, San Francisco, California). Statistical analysis used Repeated Measures ANCOVA (SPSS, v.18.0; Chicago, IL).

Results: We found that surgical patients, during the first follow-up interval (5-9 months), but not subsequently, had increased rates of atrophy for cortical gray matter and hippocampus, and lateral ventricle enlargement, as compared with nonsurgical controls. A composite score of five cognitive tests during this interval showed reduced performance for surgical patients with mild cognitive impairment.

Conclusions: Elderly subjects after surgery experienced an increased rate of brain atrophy during the initial evaluation interval, a time associated with enhanced risk for postoperative cognitive dysfunction. Although there was no difference in atrophy rate by diagnosis, subjects with mild cognitive impairment suffered greater subsequent cognitive effects.

Figures

Figure 1. Baseline comparisons for region of interest volumes

The mean baseline volume ratios are shown for control (open bars) and surgery subjects (filled bars). The top panel displays gray matter and white matter (vertical axis) as a proportion of intracranial volume (ICV). Error bars show 95% confidence intervals of the mean. The bottom panel is the same display for lateral ventricle and hippocampus. Note the difference in volumes as indicated by axis scale and bar size.

Figure 2. Lateral Ventricle volume changes in a surgical patient

Sample cortical magnetic resonance image pairs (baseline, 1st follow up) show lateral ventricle enlargement subsequent to surgery for a mild cognitive impairment (MCI) patient. The % volume change for this particular subject from the pre to post surgical interval was 7.13% (about 33% greater than the average post surgery change). White arrow indicates lateral ventricle. Black arrow indicates hippocampus.

Figure 3.A. Atrophy of Hippocampus as a function of severity group and surgery

Hippocampal volume is plotted on the vertical axis as a proportion of intracranial volume for 2 time points (horizontal axis) which include: baseline and 1st follow up. The solid lines are the control subjects and the dashed lines are the surgical subjects. NL (normal) and MCI (mild cognitive impairment) subjects are plotted separately. These plots illustrate that NL and MCI subjects have the same atrophy rate, even though MCI subjects have a lower baseline atrophy level.

Figure 3.B. Reduced Cognitive Performance as a function of severity group and surgery

The cognitive score (Mean Composite Z Score) is plotted on the vertical axis for 2 time points (horizontal axis) including: baseline and 1st follow up. The solid lines are the control subjects and the dashed lines are the surgical subjects. Normal (NL) subjects and subjects with mild cognitive impairment (MCI) are plotted separately. Only the MCI surgical subjects show a worsening performance versus the non-surgical controls.

Figure 4. A, B & C – Hippocampal, gray matter, and lateral ventricular volume change as a function of severity group and surgery

A graphical display is used to present the effects of severity group and surgery in a single bar graph. [Fig. 4.A] Setting the normal Hippocampal volume mean (top panel) equal to 100, Hippocampal volume measures for MCI subjects averaged 91.94 % (± 1.82% SE; n=62) of normal (100 %; ± 1.30 % SE; n=68) at baseline; and MCI-AD subjects were 77.68 % (± 2.27 % SE, n=34) of normal at baseline. MCI-AD subjects are MCI subjects who transitioned to AD during participation in the Alzheimer's Disease Neuroimaging Initiative. The average change in Hippocampal volume atrophy for the surgical patients during the first interval was 2.86 % (± 0.82 %; n=41) of the average normal Hippocampal volume. The background atrophy (non-surgical control patients) was 0.73% (± 0.32%; n=123). [Fig. 4.B] For the gray matter (GM) volume (middle panel) an atrophy versus normal (NL; 100 ±0.95 %) was seen of 3.52 ±0.82 % and 5.2 ±1.03% from NL to MCI and NL to MCI-AD respectively. The percent change for the first interval for surgery subjects was 1.39 ± 0.43) % and for non-surgical controls 0.25 ±0.25%. [Fig. 4.C] For the LV volume (bottom panel) an expansion versus NL (100 ± 6.83%) was seen of 15.87 ± 8.91 % and 28.54 ± 9.28% from NL to MCI and NL to MCI AD respectively. The percent change for the first interval for surgery subjects was 5.33 ± 0.85 % and for non-surgical controls 2.93 ± 0.41%.

Figure 4. A, B & C – Hippocampal, gray matter, and lateral ventricular volume change as a function of severity group and surgery

A graphical display is used to present the effects of severity group and surgery in a single bar graph. [Fig. 4.A] Setting the normal Hippocampal volume mean (top panel) equal to 100, Hippocampal volume measures for MCI subjects averaged 91.94 % (± 1.82% SE; n=62) of normal (100 %; ± 1.30 % SE; n=68) at baseline; and MCI-AD subjects were 77.68 % (± 2.27 % SE, n=34) of normal at baseline. MCI-AD subjects are MCI subjects who transitioned to AD during participation in the Alzheimer's Disease Neuroimaging Initiative. The average change in Hippocampal volume atrophy for the surgical patients during the first interval was 2.86 % (± 0.82 %; n=41) of the average normal Hippocampal volume. The background atrophy (non-surgical control patients) was 0.73% (± 0.32%; n=123). [Fig. 4.B] For the gray matter (GM) volume (middle panel) an atrophy versus normal (NL; 100 ±0.95 %) was seen of 3.52 ±0.82 % and 5.2 ±1.03% from NL to MCI and NL to MCI-AD respectively. The percent change for the first interval for surgery subjects was 1.39 ± 0.43) % and for non-surgical controls 0.25 ±0.25%. [Fig. 4.C] For the LV volume (bottom panel) an expansion versus NL (100 ± 6.83%) was seen of 15.87 ± 8.91 % and 28.54 ± 9.28% from NL to MCI and NL to MCI AD respectively. The percent change for the first interval for surgery subjects was 5.33 ± 0.85 % and for non-surgical controls 2.93 ± 0.41%.

Figure 4. A, B & C – Hippocampal, gray matter, and lateral ventricular volume change as a function of severity group and surgery

A graphical display is used to present the effects of severity group and surgery in a single bar graph. [Fig. 4.A] Setting the normal Hippocampal volume mean (top panel) equal to 100, Hippocampal volume measures for MCI subjects averaged 91.94 % (± 1.82% SE; n=62) of normal (100 %; ± 1.30 % SE; n=68) at baseline; and MCI-AD subjects were 77.68 % (± 2.27 % SE, n=34) of normal at baseline. MCI-AD subjects are MCI subjects who transitioned to AD during participation in the Alzheimer's Disease Neuroimaging Initiative. The average change in Hippocampal volume atrophy for the surgical patients during the first interval was 2.86 % (± 0.82 %; n=41) of the average normal Hippocampal volume. The background atrophy (non-surgical control patients) was 0.73% (± 0.32%; n=123). [Fig. 4.B] For the gray matter (GM) volume (middle panel) an atrophy versus normal (NL; 100 ±0.95 %) was seen of 3.52 ±0.82 % and 5.2 ±1.03% from NL to MCI and NL to MCI-AD respectively. The percent change for the first interval for surgery subjects was 1.39 ± 0.43) % and for non-surgical controls 0.25 ±0.25%. [Fig. 4.C] For the LV volume (bottom panel) an expansion versus NL (100 ± 6.83%) was seen of 15.87 ± 8.91 % and 28.54 ± 9.28% from NL to MCI and NL to MCI AD respectively. The percent change for the first interval for surgery subjects was 5.33 ± 0.85 % and for non-surgical controls 2.93 ± 0.41%.