A 77-year-old Caucasian man was diagnosed with dementia secondary to late-onset Alzheimer’s disease 30 months prior to his presentation at clinic, exhibiting behavioral disturbances, cognitive decline, and decreased ability to engage in activities of daily living. Approximately 14 months following the initial diagnosis, our patient began treatment with 10 mg of memantine per day [10, 11], though his cognitive condition continued to deteriorate, rapidly progressing to include such behavioral changes as aggressiveness and disinhibition, in addition to progressive amnesic syndrome, aphasia, bradykinesia, shuffling gait, loss of balance, and urinary incontinence. Further, our patient experienced a 20-pound weight loss, which is ordinarily indicative of poor prognosis in patients with AD [12, 13]. Analysis of cranial magnetic resonance imaging (MRI) scans revealed age-appropriate losses in volume and mild changes to the periventricular white matter (Fig. 1).
Thirteen months following initiation of memantine treatment, our patient’s total scores on the Mini-Mental State Examination (MMSE) and Functional Assessment Staging Test (FAST) were 10 and 5 points, respectively. He lost points on orientation to time and place, attention, memory, and visuospatial construction, and our patient was noticeably slower in completing the tasks.
He experienced additional difficulty in navigating turns and corners when walking, resulting in recurrent falls, and exhibited fluctuating levels of consciousness, alternating between periods of frank confusion and lucidity. However, he experienced no visual or auditory hallucinations.
A further 3 months later, and a total of 16 months following initiation of memantine treatment, our patient's experienced further deterioration of cognitive function. Our patient had fluctuating level of consciousness. His cognition fluctuated between periods of frank confusion and lucidity, however he had no visual or audial hallucinations.
He was unable to remember his name, the calendar date, day of the week, year, or place, and could not recognize family members. Additional impairments included slurred speech, expressive aphasia, loss of bowel/bladder control, and lack of coordination marked by an inability to sit, stand, or walk unassisted. Our patient became unresponsive to stimuli, with an MMSE score of 3 and a FAST score of 7. One month later, our patient’s relatives provided informed consent for treatment with 40 mg of human recombinant DNase I (1500 KU/mg) given orally three times a day in conjunction with his continued memantine therapy (10 mg daily). The DNase I was well tolerated, and no averse or unanticipated events were registered.
Our patient demonstrated considerable cognitive improvement beginning on the second day of DNase I treatment, becoming partially oriented to time and place, and once again recognizing and remembering the names of family members. He further became able to dress himself, including tying shoelaces and buttons, as well as walk independently, feed himself, and use an exercise bike. Neurologic abnormalities affecting his gait were significantly reduced. His MMSE score increased dramatically from 3 to 16, and his FAST score was reduced from 7 to 5. However, he continued to score low on the MMSE for measures of orientation to time and place, memory, and visuospatial construction.
Two months following the initiation of DNase I treatment (19 months following initiation of memantine treatment), our patient exhibited an MMSE score 18 and a FAST score of 4. Moderate improvements in memory were observed, although visuospatial construction continued to decline. He was better able to speak and interact with others, recognize relatives, and actively attend to television programs. Our patient further became able to perform calculations, play piano, chess, and walk independently.
