Hippocampal sclerosis in the elderly: genetic and pathologic findings, some mimicking Alzheimer disease clinically.

BACKGROUND: Hippocampal sclerosis (HpScl) in the elderly is often associated with neurodegeneration. METHODS: We studied the clinical and pathologic features of HpScl in 205 consecutive patients with dementia who came to autopsy from 1997 to 2008, focusing on associations with TAR DNA-binding protein 43 (TDP-43) pathology and allelic variants in the progranulin (GRN) and apolipoprotein E (APOE). RESULTS: Of the 205 dementia patients, 28 had HpScl (14%). TDP-43 pathology was more frequent in cases with HpScl compared with those without HpScl (89% vs. 24%). GRN rs5848 T-allele but not APOE ε4 was associated with HpScl. In cases of HpScl with TDP-43 pathology and age of onset after 75 years (n=11), 8 had Alzheimer disease (AD)-like amnestic syndrome, but most (6 of 8) had pathology not consistent with AD (Braak stage III or less), including 4 with frontotemporal lobar degeneration with TDP, 1 with diffuse Lewy body disease, and 1 with "pure HpScl." CONCLUSIONS: HpScl is common in an elderly cohort with dementia, occurring in 14% of the cases in this series, and 89% have TDP-43 pathology, often associated with a risk variant in GRN. Patients with HpScl who present after the age of 75 years often have presentations consistent with AD, but at autopsy have non-Alzheimer pathologies. Elderly patients with HpScl may be mistaken for AD.

Polysomnographic findings in dementia with Lewy bodies.

INTRODUCTION: The clinical features of dementia with Lewy bodies (DLB) during wakefulness are well known. Other than rapid eye movement (REM) sleep behavior disorder, only limited data exists on other sleep disturbances and disorders in DLB. We sought to characterize the polysomnographic (PSG) findings in a series of DLB patients with sleep-related complaints. METHODS: Retrospective study of patients with DLB who underwent clinical PSG at Mayo Clinic, Rochester or Mayo Clinic, Jacksonville over an almost 11-year span for evaluation of dream enactment behavior, excessive nocturnal movements, sleep apnea, hypersomnolence, or insomnia. The following variables were analyzed: respiratory disturbance index (RDI) in disordered breathing events/hour, periodic limb movement arousal index, arousals for no apparent reason (AFNAR), total arousal index, presence of REM sleep without atonia, and percent sleep efficiency. RESULTS: Data on 78 patients (71 male, 7 female) were analyzed. The mean age was 71±8 years. Seventy-five (96%) patients had histories of recurrent dream enactment during sleep with 83% showing confirmation of REM sleep without atonia±dream enactment during PSG. Mean RDI=11.9±5.8, periodic limb movement arousal index =5.9±8.5, arousals for no apparent reason index=10.7±12.0, and total arousal index=26.6±17.4. Sleep efficiency was <80% in 72% of the sample, <70% in 49%, and <60% in 24%. In patients who did not show evidence of significant disordered breathing (23 with RDI<5), 62% of arousals were AFNARs. In those patients who had significant disordered breathing (55 with RDI≥5), 36% of arousals were AFNARs. Six patients underwent evaluations with PSG plus multiple sleep latency test. Two patients had mean initial sleep latencies of <5 minutes, and both had RDI<5. No patient had any sleep onset REM periods. Nineteen patients have undergone neuropathologic examination, and 18 have had limbic-predominant or neocortical-predominant Lewy body pathology. One had progressive supranuclear palsy, but no REM sleep was recorded in prior PSG. CONCLUSIONS: In patients with DLB and sleep-related complaints, several sleep disturbances in addition to REM sleep behavior disorder are frequently present. In this sample, about 3/4 had a significant number of arousals not accounted for by a movement or breathing disturbance, and the primary sleep disorders do not seem to entirely account for the poor sleep efficiency in DLB, especially in those without a significant breathing disorder. Further studies are warranted to better understand the relationship between disturbed sleep, arousal, and DLB; such characterization may provide insights into potential avenues of treatment of symptoms that could impact quality of life.