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Posterior cortical atrophy or the “visual variant” of Alzheimer’s disease is a clinical syndrome with visual agnosia, some or all the components of Balint’s syndrome, transcortical sensory aphasia, and Gerstmann’s syndrome.1 Although pathologically heterogeneous, several necropsy studies on patients with posterior cortical atrophy have shown Alzheimer’s disease pathology.1 We report a patient who presented with the features of posterior cortical atrophy who later developed mild parkinsonism, visual hallucinations, and delusions. Neuropathological evaluation revealed combined Alzheimer’s disease and Lewy body disease.
A right handed retired diesel mechanic, with 12 years of formal education, was referred for evaluation of an “unusual dementia.” His difficulties started at the age of 58 with the insidious onset of visuospatial dysfunction. Initially he was not able to fill out bank deposit slips or write numbers correctly. He had been an avid reader but had to re-read material in order to comprehend it, and unsuccessfully used a card to keep his eyes focused when reading. He was not able to locate the refrigerator door handle until he groped over the surface to find it.
His wife revealed that when he was 61 he was having difficulties working as a mechanic. Also, he could not see other cars and obstacles while driving, and he stopped driving at the age of 63 after being involved in two motor vehicle accidents. He developed progressive difficulties with performing calculations, writing, receptive language, and recent memory. Despite the cognitive difficulties, he retained insight in his disorder.
When he was 62, his wife noted that he moved in a stiff manner, did not swing his left arm, and acted “like a little old man.” At age 67, he developed well formed visual hallucinations (he would see bugs, spiders, and people) and paranoid delusions (he expressed concern that people were tearing away his home). He developed personality changes and at times was confrontational. He became entirely dependent on his wife for all of his activities of daily living. No features of REM sleep behaviour disorder were ever noted by the family.
The initial neurological evaluation at the Mayo Clinic when he was 67 revealed a complete Balint’s syndrome, a partial Gerstmann’s syndrome, and impairment on visuospatial tasks and recall. On language examination he had paraphasic errors and neologisms. He also showed bradykinesia, a slow wide based gait with reduced arm swing bilaterally, mild generalised rigidity, postural but not resting tremor, and right limb apraxia. He had limited upgaze but preserved downward and horizontal gaze. Visual acuity was 20/80 and 20/100 in the right and left eye, respectively. There was no alien limb phenomenon, dystonia, or myoclonus.
Neuropsychological testing showed impairment in verbal skills and verbal memory and the inability to complete the visual tasks. Magnetic resonance imaging and single photon emission computed tomography of the brain showed, respectively, marked asymmetrical (left more than right) parietal-occipital cortical atrophy and hypoperfusion.
Towards the end of his life, he became wheelchair bound and was transferred to a chronic care facility. He developed more behavioural problems, declining vision, and persistent visual hallucinations and delusions. He was unable to recognise family members by sight or sound. He died at 71 years of age.
His past medical history was only significant for a total thyroidectomy for cancer, for which he was on thyroid replacement. There was no family history of any neurodegenerative disorder.
At necropsy examination, standard brain fixation and dissection was undertaken. Tissue sections were cut and stained with haematoxylin and eosin, Bielchowsky silver stain, and immunohistochemically with antibodies to tau (Endogen-AT8), amyloid protein, and synuclein (Zimed-LB509).
The brain weighed 1136 g. Focal, asymmetrical (left greater than right) parieto-occipital cortical atrophy and mild pallor of the substantia nigra were observed. The basal ganglia, thalamus, and cerebellum appeared normal. Microscopically, moderate to frequent diffuse and neuritic plaques and frequent neurofibrillary tangles were seen in limbic structures. Accentuated neuronal loss and increased neurofibrillary tangle density were noted in the parieto-occipital lobes. The findings satisfied criteria for Alzheimer’s disease by Braak and Braak staging (stage VI/VI)2 and by the National Institute on Aging and Reagan Institute working group on diagnostic criteria for the neuropathological assessment of Alzheimer’s disease (high likelihood).2 In addition, synuclein positive Lewy bodies, pale bodies, and Lewy neurites were found in the substantia nigra, amygdala, entorhinal cortex, and cingulate gyrus; however, the substantia nigra was less affected than the limbic structures, where synuclein pathology was severe. These findings are consistent with a diagnosis of transitional Lewy body disease.3
The clinical syndrome of posterior cortical atrophy is characterised by prominent dysfunction of the neuronal networks in the biparietal and occipital cortices and does not imply an underlying pathology; neuropathological examination in most cases shows neurofibrillary tangles and neuritic plaques characteristic of Alzheimer’s disease, but with a higher concentration of the pathology located in the primary visual cortex and visual association areas.1 The predominant features of posterior cortical atrophy are followed by dementia more typical of Alzheimer’s disease.1 Visual hallucinations and parkinsonism are distinctly uncommon but are recognised features, in addition to fluctuations in cognition that are considered characteristic of dementia with Lewy bodies.3 Pathologically, the latter is characterised by the presence of Lewy body disease, with limbic or neocortical Lewy bodies.3
Our case presented with the typical features of posterior cortical atrophy, and findings of Alzheimer’s disease and Lewy body disease were revealed on neuropathological examination. To our knowledge, there have been no previous pathological reports of cases of posterior cortical atrophy with coexisting Lewy body disease. The visual hallucinations and parkinsonism in our patient were consistent with dementia with Lewy bodies, and there was evidence of transitional Lewy body disease at necropsy. The other major features of posterior cortical atrophy would be consistent with the prominent Alzheimer’s pathology in occipito-parietal cortices.
Interestingly, few patients with posterior cortical atrophy experience visual hallucinations as an initial symptom despite the marked pathology affecting the primary visual and visual association cortices. Our patient also had clinical features suggesting corticobasal degeneration.4 Although there are reports of prominent visuospatial impairment or Balint’s syndrome in clinically diagnosed and pathologically diagnosed corticobasal degeneration,5 visual hallucinations are almost non-existent in corticobasal degeneration.6 This suggests that visual hallucinations and parkinsonism in the setting of cognitive impairment reflect underlying Lewy body disease rather than corticobasal degeneration.6 Our case supports this contention. We suggest that underlying Lewy body disease should be considered in any case of posterior cortical atrophy associated with parkinsonism and particularly visual hallucinations.
Supported by grants AG 16574 and AG 07216 from the National Institute on Aging. We extend our appreciation to the family for participating in research on aging and dementia.
Competing interests: none declared
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