Griselda J. Garrido

Cognitive and brain changes associated with ischaemic heart disease and heart failure

AIMS It is unclear whether the cognitive dysfunction associated with heart failure (HF) is due to HF or comorbid conditions such as ischaemic heart disease (IHD). This study aimed to determine whether, compared with controls with and without IHD, adults with systolic HF show evidence of cognitive impairment and cerebral grey matter (GM) loss. METHODS AND RESULTS Cross-sectional study of 35 participants with HF, 56 with IHD, and 64 controls without either HF or IHD. Subjects were older than 45 years and free of overt cognitive impairment. We acquired magnetic resonance images and used SPM8 to determine regional differences in cerebral GM volume. Participants with HF had lower scores than controls without IHD on immediate memory, long delay recall and digit coding, whereas those with IHD had lower long delay recall scores than controls without IHD. Compared with controls without IHD, participants with HF showed evidence of GM loss in the left cingulate, the right inferior frontal gyrus, the left middle and superior frontal gyri, the right middle temporal lobe, the right and left anterior cingulate, the right middle frontal gyrus, the inferior and pre-central frontal gyri, the right caudate, and occipital-parietal regions involving the left precuneus. The loss of GM followed a similar, less extensive, pattern when we compared participants with HF and IHD. CONCLUSION Adults with HF have worse immediate and long-term memory and psychomotor speed than controls without IHD. Heart failure is associated with changes in brain regions that are important for demanding cognitive and emotional processing.

24-month effect of smoking cessation on cognitive function and brain structure in later life

BACKGROUND Observational studies investigating the association between smoking, cognitive decline and dementia have produced conflicting results. We completed this trial to determine if smoking cessation decreases the progression of cognitive decline in later life. METHODS We recruited older smokers (n=229) and never smokers (n=98) and invited smokers to join a smoking cessation trial. The primary outcome of interest was change in Alzheimers Disease Assessment Scale cognitive subscale (ADAS-cog) scores over 24 months. Secondary measures included the Logical Memory test and changes in gray matter density. Successful smoking cessation was defined as a minimum of 547 smoking free days during follow up. RESULTS The ADAS-cog scores of unsuccessful quitters (UQ) increased (i.e., became worse) 1.1±0.3 and 1.2±0.4 points more than the scores of never smokers (NS) (p=0.001) and successful quitters (SQ) (p=0.006) respectively over the 24 months of follow up. Similarly, the scores of UQ declined (i.e., became worse) relative to NS on measures of immediate (p=0.004) and delayed recall (p=0.029). All analyses were adjusted for age, years of education, baseline cognitive performance, alcohol use, depression scores, and the presence of chronic respiratory disease. Thirty-six NS, 18 SQ and 48 UQ completed the imaging substudy. Compared with NS, UQ showed a disproportional loss of gray matter density in the right thalamus, right and left inferior semi-lunar lobule, as well as left superior and inferior parietal lobule over 24 months. SQ showed loss of gray matter compared with NS in the right middle and inferior occipital gyri, right and left culmen, and the left superior frontal gyrus. We did not find any brain regions in which UQ had lost more gray matter than SQ over 2 years. CONCLUSION These results are consistent with the hypothesis that smoking causes cognitive decline and loss of gray matter tissue in the brain over time.

Brain and mood changes over 2 years in healthy controls and adults with heart failure and ischaemic heart disease

Heart failure (HF) has been associated with cognitive dysfunction, a high prevalence of mood disorders, and a relative loss of grey matter in several brain regions. This study aimed to determine if, compared with controls with and without ischaemic heart disease (IHD), adults with HF show evidence of progressive loss of cerebral grey matter, and whether morphological changes are associated with changes in cognition, depression and anxiety symptoms over a follow‐up period of 2 years.

Coronary heart disease is associated with regional grey matter volume loss: implications for cognitive function and behaviour.

Coronary heart disease (CHD) has been associated with impaired cognition, but the mechanisms underlying these changes remain unclear. We designed this study to determine whether adults with CHD show regional brain losses of grey matter volume relative to controls. We used statistical parametric mapping (SPM5) to determine regional changes in grey matter volume of T1‐weighted magnetic resonance images of 11 adults with prior history of myocardial infarction relative to seven healthy controls. All analyses were adjusted for total grey and white matter volume, age, sex and handedness. CHD participants showed a loss of grey matter volume in the left medial frontal lobe (including the cingulate), precentral and postcentral cortex, right temporal lobe and left middle temporal gyrus, and left precuneus and posterior cingulate. CHD is associated with loss of grey matter in various brain regions, including some that play a significant role in cognitive function and behaviour. The underlying causes of these regional brain changes remain to be determined.

Cognitive Deficits in Machado–Joseph Disease Correlate with Hypoperfusion of Visual System Areas

Cognitive and olfactory impairments have previously been demonstrated in patients with spinocerebellar ataxia type 3 (SCA3), also known as Machado–Joseph disease (MJD)—SCA3/MJD. We investigated changes in regional cerebral blood flow (rCBF) using single-photon emission computed tomography (SPECT) imaging in a cohort of Brazilian patients with SCA3/MJD. The aim of the present study was to evaluate the correlation among rCBF, cognitive deficits, and olfactory dysfunction in SCA3/MJD. Twenty-nine genetically confirmed SCA3/MJD patients and 25 control subjects were enrolled in the study. The severity of cerebellar symptoms was measured using the International Cooperative Ataxia Rating Scale and the Scale for the Assessment and Rating of Ataxia. Psychiatric symptoms were evaluated by the Hamilton Anxiety Scale and Beck Depression Inventory. The neuropsychological assessment consisted of Spatial Span, Symbol Search, Picture Completion, the Stroop Color Word Test, Trail Making Test (TMT), and Phonemic Verbal Fluency. Subjects were also submitted to odor identification evaluation using the 16-item Sniffin’ Sticks. SPECT was performed using ethyl cysteine dimer labeled with technetium-99m. SCA3/MJD patients showed reduced brain perfusion in the cerebellum, temporal, limbic, and occipital lobes compared to control subjects (pFDR <0.001). A significant positive correlation was found between the Picture Completion test and perfusion of the left parahippocampal gyrus and basal ganglia in the patient group as well as a negative correlation between the TMT part A and bilateral thalamus perfusion. The visuospatial system is affected in patients with SCA3/MJD and may be responsible for the cognitive deficits seen in this disease.

Homocysteine, Grey Matter and Cognitive Function in Adults with Cardiovascular Disease

Background Elevated total plasma homocysteine (tHcy) has been associated with cognitive impairment, vascular disease and brain atrophy. Methods We investigated 150 volunteers to determine if the association between high tHcy and cerebral grey matter volume and cognitive function is independent of cardiovascular disease. Results Participants with high tHcy (≥15 µmol/L) showed a widespread relative loss of grey matter compared with people with normal tHcy, although differences between the groups were minimal once the analyses were adjusted for age, gender, diabetes, hypertension, smoking and prevalent cardiovascular disease. Individuals with high tHcy had worse cognitive scores across a range of domains and less total grey matter volume, although these differences were not significant in the adjusted models. Conclusions Our results suggest that the association between high tHcy and loss of cerebral grey matter volume and decline in cognitive function is largely explained by increasing age and cardiovascular diseases and indicate that the relationship is not causal.

Memory Networks in Tinnitus: A Functional Brain Image Study

Tinnitus is characterized by the perception of sound in the absence of an external auditory stimulus. The network connectivity of auditory and non-auditory brain structures associated with emotion, memory and attention are functionally altered in debilitating tinnitus. Current studies suggest that tinnitus results from neuroplastic changes in the frontal and limbic temporal regions. The objective of this study was to use Single-Photon Emission Computed Tomography (SPECT) to evaluate changes in the cerebral blood flow in tinnitus patients with normal hearing compared with healthy controls. Methods: Twenty tinnitus patients with normal hearing and 17 healthy controls, matched for sex, age and years of education, were subjected to Single Photon Emission Computed Tomography using the radiotracer ethylenedicysteine diethyl ester, labeled with Technetium 99 m (99 mTc-ECD SPECT). The severity of tinnitus was assessed using the “Tinnitus Handicap Inventory” (THI). The images were processed and analyzed using “Statistical Parametric Mapping” (SPM8). Results: A significant increase in cerebral perfusion in the left parahippocampal gyrus (pFWE <0.05) was observed in patients with tinnitus compared with healthy controls. The average total THI score was 50.8+18.24, classified as moderate tinnitus. Conclusion: It was possible to identify significant changes in the limbic system of the brain perfusion in tinnitus patients with normal hearing, suggesting that central mechanisms, not specific to the auditory pathway, are involved in the pathophysiology of symptoms, even in the absence of clinically diagnosed peripheral changes.

Psychosis in Machado–Joseph Disease: Clinical Correlates, Pathophysiological Discussion, and Functional Brain Imaging. Expanding the Cerebellar Cognitive Affective Syndrome

Machado–Joseph disease (MJD) is the most common spinocerebellar ataxia worldwide with a broad range of clinical manifestations, but psychotic symptoms were not previously characterized. We investigated the psychiatric manifestations of a large cohort of Brazilian patients with MJD in an attempt to characterize the presence of psychotic symptoms. We evaluated 112 patients with clinical and molecular diagnosis of MJD from February 2008 to November 2013. Patients with psychotic symptoms were referred to psychiatric evaluation and brain perfusion single-photon emission computed tomography (SPECT) analysis. A specific scale—Positive and Negative Syndrome Scale (PANSS)—was used to characterize psychotic symptoms in MJD patients. We also performed an autopsy from one of the patients with MJD and psychotic symptoms. Five patients presented psychotic symptoms. Patients with psychotic symptoms were older and had a late onset of the disease (p < 0.05). SPECT results showed that MJD patients had significant regional cerebral blood flow (rCBF) decrease in the cerebellum bilaterally and vermis compared with healthy subjects. No significant rCBF differences were found in patients without psychotic symptoms compared to patients with psychotic symptoms. The pathological description of a patient with MJD and psychotic symptoms revealed severe loss of neuron bodies in the dentate nucleus and substantia nigra. MJD patients with a late onset of the disease and older ones are at risk to develop psychotic symptoms during the disease progression. These clinical findings may be markers for an underlying cortical–cerebellar disconnection or degeneration of specific cortical and subcortical regions that may characterize the cerebellar cognitive affective syndrome.