Cognitive consequences of COVID-19 in older adults with cognitive impairment

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with significant morbidity and mortality that is well documented. This includes significant central nervous system (CNS) involvement that ranges from acute delirium to meningoencephalitis. While acute symptoms and manifestations have been noted, long-term neuropsychiatric and cognitive outcomes remain unclear in convalescent COVID-19 patients. Characterizing the convalescence is particularly important since 80% recover, yet the relationship between exacerbated cognitive dysfunction and COVID-19 remains unclear. We describe 3 adults above age 65 who reported worsening cognitive symptoms in the convalescent stage of COVID-19. METHODS: Three adults above the age of 65 who noted worsening cognitive difficulties after SARS-CoV-2 infection and COVID-19 were evaluated in the Memory Clinic of the Duke Neurological Disorders Clinic. Electronic medical records were retrospectively reviewed. Exam included a comprehensive neurological evaluation, formal neuropsychological evaluation, and neuroimaging. Prior history was collected for comparison with their current clinical evaluation profile data. RESULTS: Patient 1 is a 69 year old diabetic, hypertensive male with a history of depression and a first-order relative and a maternal aunt with late-onset Alzheimer's disease dementia who presented for evaluation of memory loss first noted about one year prior but had significantly worsened in the five months since his recovery from COVID-19. He had documented antibodies to SARS-CoV-2. The patient reported forgetting when he had eaten and now evinces navigation issues even when driving on familiar roads. Head CT without contrast obtained before COVID-19 infection showed mild bilateral hippocampal atrophy. He scored 4/8 on the AD8 Dementia Screening and 20/30 on the Montreal Cognitive Assessment (MoCA). PHQ9 was 10, GAD7 was 0, and NPI was 1. Formal neuropsychological evaluation data were collected. A diagnosis of late-onset Alzheimer's disease without behavioral disturbance was made during his clinic visit. Donezepil was started. Other comorbidities included vitamin B12 deficiency, atrial fibrillation, congestive heart failure, chronic obstructive pulmonary disease, obstructive sleep apnea, and morbid obesity. Patient 2 is a 68 year old male with a history of anxiety, depression, and attention deficit disorder who presented for evaluation of poor memory, inability to “visually map,” and daily “senior moments” as well as a prolonged period of confusion while driving four months after recovering from COVID-19. He had documented antibodies to SARS-CoV-2. He had transient memory problems two years ago that improved after changing his bupropion dosage. He also takes fluoxetine. He now regularly misplaces objects and often stops a task midway through, thinking that he completed it. His GDS score was 5. Head CT was unremarkable. MRI of the brain demonstrated mild hippocampal and biparietal lobe atrophy as well as mild cerebral white matter disease. He scored 7/8 on the AD8 Dementia Screening and 27/30 on the MoCA. A diagnosis of dementia with behavioral disturbance was made. PHQ9 was 9, GAD7 was 6, and NPI was 7. B12 was normal. There is no family history of cognitive impairment. Patient 3 is a 76-year-old female with a history of bipolar 1, diabetes, hypothyroidism, hyperlipidemia who presented for evaluation of memory loss that started 6 months ago but worsened since she had recovered from COVID-19 diagnosed about 8 weeks earlier. After testing positive, she was hospitalized for 3 weeks due to acute encephalopathy attributed to lithium toxicity. She was also taking trazodone. Her GDS score was 7. She scored 8/8 on the AD8 Dementia Screening. MoCA could not be completed. PHQ9 was 3, GAD7 was 9, and NPI was 19. Formal neuropsychological evaluation data were collected. Head CT without contrast three weeks after COVID-19 diagnosis showed calcification in the right basal ganglia, a mild hypodense signal periventricularly, and gray-white differentiation. Brain MRI without contrast showed subtle hippocampal and perisylvian atrophy on T1, mild to moderate parietal lobe atrophy bilaterally, and mild to moderate periventricular leukoaraiosis/white matter hyperintensities on FLAIR sequence. A diagnosis of dementia without behavioral disturbance was made. There is a family history of bipolar disorder in siblings and cognitive impairment in her father but no specific diagnosis of dementia. CONCLUSIONS: This case series describes the exacerbation of pre-existing psychiatric and cognitive conditions after COVID-19 recovery in 3 older adults with formal neuropsychological evaluation data. Longitudinal investigation of convalescent patients is warranted to better clinically characterize and provide insight into the long-term effects of COVID-19. This will allow further investigation into the pathophysiology regarding the long-term consequences of SARS-CoV-2 infection. FUNDING: Not Applicable.