CAIDE Dementia Risk Score, Alzheimer and cerebrovascular pathology: a population-based autopsy study.

BACKGROUND: CAIDE Dementia Risk Score is a tool for estimating dementia risk in the general population. Its longitudinal associations with Alzheimer or vascular neuropathology in the oldest old are not known. AIM: To explore the relationship between CAIDE Dementia Risk Score at baseline and neuritic plaques, neurofibrillary tangles, cerebral infarcts and cerebral amyloid angiopathy (CAA) after up to 10-year follow-up in the Vantaa 85 +  population. METHODS: Study population included 149 participants aged ≥85 years, without dementia at baseline, and with available clinical and autopsy data. Methenamine silver staining was used for ß-amyloid and modified Bielschowsky method for neurofibrillary tangles and neuritic plaques. Macroscopic infarcts were identified from cerebral hemispheres, brainstem and cerebellum slices. Standardized methods were used to determine microscopic infarcts, CAA and α-synuclein pathologies. The CAIDE Dementia Risk Score was calculated based on scores for age, sex, BMI, total cholesterol, systolic blood pressure, physical activity and APOEε4 carrier status (range 0-18 points). RESULTS: A CAIDE Dementia Risk Score above 11 points was associated with more cerebral infarctions up to 10 years later: OR (95% CI) was 2.10 (1.06-4.16). No associations were found with other neuropathologies. CONCLUSION: In a population of elderly aged ≥85 years, higher CAIDE Dementia Risk Score was associated with increased risk of cerebral infarcts.

Intracranial Suppurative Complications of Sinusitis.

BACKGROUND: Intracranial complications of paranasal sinusitis have become rare due to widespread and early use of antibiotics. Potentially life-threatening intracranial complications of sinusitis include subdural empyema, epidural and intracerebral abscess, meningitis, and sinus thrombosis. Patients with intracranial complication of sinusitis can present without neurological signs, which may delay diagnosis and correct treatment. AIMS: Our aim was to evaluate the diagnostics, treatment, and outcome of sinusitis-related intracranial infections at our tertiary referral hospital with a catchment area of 1.9 million people. MATERIALS AND METHODS: We retrospectively collected data on all patients diagnosed and treated with an intracranial infection at the Helsinki University Hospital, Helsinki, Finland, during a 10-year period between 2003 and 2013. RESULTS: Six patients were diagnosed to have a sinusitis-related intracranial infection. Four patients had an epidural abscess, one both an epidural abscess and a subdural empyema and one a subdural empyema. The most common presenting complaint was headache (100%) followed by fever (83%), vomiting (50%), nasal congestion (50%), forehead lump (34%), and neck stiffness (17%). All patients were managed surgically. Most (83%) patients recovered to premorbid state without neurological sequelae. One patient died intraoperatively. CONCLUSION: Patients with a sinusitis-related intracranial suppuration typically present with signs of raised intracranial pressure rather than signs of sinusitis. Most are likely to need neurosurgical intervention and evacuation of the abscess without delay.

Frontal lobe white matter hyperintensities and neurofibrillary pathology in the oldest old.

BACKGROUND: Current studies suggest an interaction between vascular mechanisms and neurodegenerative processes that leads to late-onset Alzheimer disease (AD). We tested whether AD pathology was associated with white matter hyperintensities (WMH) or cerebral infarcts in the oldest old individuals. METHODS: Brains from 132 subjects over 85 years old, who came to autopsy from the Vantaa 85+ population-based cohort, were scanned by postmortem MRI and examined for neuropathologic changes. Coronal images were analyzed to determine the degree of frontal and parietal periventricular WMH (PVWMH) and deep WMH (DWMH) and cerebral infarcts. Neuropathologic variables included Consortium to Establish a Registry for Alzheimer's Disease scores for neuritic plaques and Braak staging among subjects in 5 groups: normal aging (NA), borderline with insufficient AD pathology, AD, AD plus other pathology, and other primary degenerative diseases. RESULTS: Frontal DWMH were detected in >50% of the sample. Both frontal PVWMH and DWMH were significantly more extensive in the AD group compared to the NA group or the NA and borderline groups combined. Frontal PVWMH and DWMH were also associated with increased Braak staging (p = 0.03) and the neuritic plaque load (p = 0.01). Further analysis revealed there were a greater number of cerebral infarcts associated with frontal DWMH (p = 0.03) but not with frontal PVWMH. CONCLUSIONS: Our study showed an association between neurofibrillary pathology and frontal PVWMH and DWMH (rather than parietal), as a surrogate of small vessel disease, particularly in very old community-dwelling individuals.

The significance of medial temporal lobe atrophy: a postmortem MRI study in the very old.

BACKGROUND: Medial temporal lobe atrophy (MTA) is a sensitive radiologic marker for Alzheimer disease (AD) and associated with cognitive impairment. The value of MTA in the oldest old (>85 years old) is largely unknown. METHODS: A total of 132 formalin-fixed brains from the Vantaa 85+ community-based study were subjected to postmortem MRI. Visual ratings of MTA were determined in a blinded fashion and compared with neuropathologic findings and clinical assessment (dementia according to Diagnostic and Statistical Manual of Mental Disorders-III-R). RESULTS: A strong relationship was found between MTA scores and Alzheimer pathology (p < 0.001). The previously proposed cutoff MTA score >2 correctly excluded subjects with no or borderline Alzheimer-type pathology (45/48), but was not very sensitive for AD (modified National Institute on Aging-Reagan Institute criteria). MTA scores >2 were also found in subjects with other primary neurodegenerative hippocampal pathology including hippocampal sclerosis, Lewy-related pathology, and argyrophilic grain disease, either alone or in combination with Alzheimer-type pathology. High MTA scores were associated with clinical dementia-in this subgroup, sensitivity was 63% and specificity 69% for AD. CONCLUSION: Medial temporal lobe atrophy (MTA) on postmortem MRI is sensitive to primary degenerative hippocampal pathology in the very old, but not specific for Alzheimer-type pathology. MTA scores of 2 or less are not frequently associated with dementia.

Reappraisal of a consecutive autopsy series of patients with primary degenerative dementia: Lewy-related pathology.

Dementia with Lewy bodies (DLB) is a common but underdiagnosed dementing disorder. Its criteria were defined in 1996, and revised in 2005. DLB is characterised neuropathologically by widely distributed cortical Lewy bodies (LBs), usually associated with Alzheimer-type pathology. We have re-evaluated the neuropathology of 55 autopsied patients with clinically diagnosed primary degenerative dementia to determine the frequency of DLB in this cohort, which was originally examined when neither the entity of DLB nor its diagnostic criteria had been defined. We also evaluated how discovery of a new entity affects previous diagnoses. Of the 55 brains, 16 (29%) contained LBs. All 16 originally had a neuropathological diagnosis of Alzheimer's disease (AD). 11 (20%) fulfilled the neuropathological criteria for DLB. Three patients had AD with LBs in the brain stem only, and two patients had LBs in the limbic cortex only. Because the criteria and reliable markers for DLB were not available at the time of the autopsies, the diagnosis of DLB had not been possible. The common co-occurrence of AD-type pathology in DLB makes the clinical diagnosis of DLB problematic even today. This study also raises the question of the relative significances of Lewy-related and AD-type pathologies to the development of dementia.