Sport history. This participant played football in high school and in the CFL for 6 years. He had many concussions.
Clinical findings. When the patient was 55-years old, his sister noted that he had difficulty with short-term memory and that he was less able to formulate arguments. He subsequently developed visuospatial impairments and was reported to get lost in familiar environments. He developed apathy and agitation, and became very depressed. His loss of judgment led to bankruptcy and at the age of 66, he became a ward of the state. He developed language deficits and exhibited word substitution, and was incoherent at times. He became depressed and had paranoid delusions. His past medical history was unremarkable except for recurrent phlebitis. The patient developed lung cancer and died of its complications at age 67.
Family history. His paternal grandfather had vascular dementia.
Neuropathological findings. Neuropathological examination revealed a brain weight of 1400 g with mild atrophy of the frontal and temporal lobes (Figure 1). There were findings consistent with widespread metastatic disease from a lung carcinoma and severe vascular atherosclerotic disease with recent multifocal brain infarctions. There was also thinning of the olfactory tracts and hypothalamus. Coronal sections of the brain showed an enlarged ventricular system, corpus callosum atrophy, and cavum septi pellucidi. Pigmentation of the SN appeared within normal limits (Figure 1).
Microscopically, there was mild to moderate neuronal loss and gliosis in CA1, subiculum, entorhinal cortex, amygdala, mammillary bodies, and medial thalamic nuclei. There was granulovacuolar degeneration noted in the CA1 and subiculum area with pronounced subpial gliosis in the trans-entorhinal cortex. Immunohistochemically, there was widespread tau-positive neurofibrillary and astrocytic tangles in multiple layers (superficial > deep) of the cortex, especially in the depths of sulci (Figure 2). There were some inclusions noted in the gyral crowns. These inclusions were consistently found in all cortical areas with a predilection for the medial temporal, hippocampus, and amygdala areas. NFTs were also noted in thalamus, peri-ventricular hypothalamic areas extending into the mamillary bodies, the nucleus basalis of Meynert and clustering around blood vessels. Beta-amyloid staining revealed amyloid plaques. TDP-43 and alpha-synuclein staining were unremarkable.
Neuropathological diagnosis. Overall, neuropathological findings and the distribution of tauopathy were compatible with changes seen in CTE. Although there were multiple infarcts noted, they appeared to be relatively recent infarcts and could not fully account for the participant's longer-term dementia.
Sport history. This patient played in the CFL for 8 years. He had many concussions.
Clinical findings. At age 64, he began to show behavioral changes, including anger, poor judgment, and irritability. Over the next few years his memory worsened and he began to get lost. He then began having hallucinations of strangers in his home and also developed some misidentification for others and himself. He seemed to no longer recognize himself as he would attack mirrors when he walked in front of them. He developed delusions that people were stealing from him and had episodes of aggression and agitation, as well as impaired motor function. The patient died at age 74.
Family history. His mother had late onset AD and his father had late onset dementia.
Neuropathological findings. His brain was atrophic with a weight of 1300 g after fixation with moderate ventricular enlargement (Figure 1). SN showed normal pigmentation.
Microscopic examination revealed numerous NFTs in neurons of the deep cortical layers (Figure 2). These were concentrated to the trans-entorhinal cortex, hippocampus, and isocortex with significant extension into the primary visual cortex. There was also significant presence of tangles in nucleus basalis of Meynert, amygdala, substantia nigra, and in the Edinger-Westphal nucleus. Supplementing the tangles were numerous dense-core, beta-amyloid positive plaques. No evident TDP-43 or alpha-synuclein staining was seen.
Neuropathological diagnosis. Overall, findings were consistent with severe AD (Braak Stage VI/VI) without any pathological evidence of CTE.
Sport history. He began playing football in high school and played seven years in the CFL. He suffered multiple concussions.
Clinical findings. At age 48, his wife noted that he was becoming withdrawn and then he gradually changed from a confident, assertive, energetic person to an anxious, insecure, and more lethargic person. At age 50, he noted his handwriting had become messier, and also complained of some cramping and numbness in his feet and decreased ability for playing baseball. He also began exhibiting memory deficits, which became progressively worse over the subsequent years. A few years later, his wife noted his speech was slurred and hypophonic and the slowing of his movements became more apparent. He did not have a tremor. At age 54, his wife became concerned about his judgment based on poor business decisions. He became obsessive about bladder incontinence and went to the bathroom multiple times a day, yet seemed incongruously unperturbed when accidents did happen. By age 55, he was having repeated episodes of loss of bladder control. He had vivid dreams that he was convinced were real, but no REM sleep behavior disorder. His judgment continued to deteriorate, and he became less attentive to hygiene. He had delusions and hallucinations, but these stopped with discontinuation of Sinemet therapy. He eventually had episodes of agitation and developed great difficulty ambulating. He had prosopagnosia at age 58. At that time, he began showing difficulty recalling the names of his children. His past medical history was unremarkable. The patient died at age 63.
Family history. No family history of a neurodegenerative disease.
Neuropathological findings. Neuropathological examination showed a brain of normal weight (1450 g) with mild diffuse cortical atrophy. Ventricles were mildly dilated (Figure 1).
On microscopic examination, there was diffuse Lewy body disease with Lewy bodies and Lewy neuritis in the cerebral cortex, olfactory bulbs, indusium griseum, SN and limbic system, including the CA2-4 subdivisions of the hippocampus (Figure 2). There was extensive neuronal loss in the SN pars compacta, locus ceruleus, dorsal nucleus of CN X and nucleus basalis of Meynert. There was very limited tau labeling in the hippocampus, the amygdala, and peri-amygdala cortex. There was, however, widespread distribution of diffuse amyloid plaques. TDP-43 staining in this case was unremarkable.
Neuropathological diagnosis. Overall, this case showed typical changes of long-term progressive PD. While the tau-deposits in the hippocampal area were age-appropriate Alzheimer-type changes (Braak Stage II/VI), there was no evidence of AD. There was also no pathological evidence consistent with CTE.