Association of Long-Term Dietary Fat Intake, Exercise, and Weight with Later Cognitive Function in the Finnish Diabetes Prevention Study.

OBJECTIVES: To investigate associations of long-term nutrient intake, physical activity and obesity with later cognitive function among the participants in the Finnish Diabetes Prevention Study, in which a lifestyle intervention was successful in diabetes prevention. DESIGN: An active lifestyle intervention phase during middle age (mean duration 4 years) and extended follow-up (additional 9 years) with annual lifestyle measurements, followed by an ancillary cognition assessment. SETTING: 5 research centers in Finland. PARTICIPANTS: Of the 522 middle-aged, overweight participants with impaired glucose tolerance recruited to the study, 364 (70%) participated in the cognition assessment (mean age 68 years). MEASUREMENTS: A cognitive assessment was executed with the CERAD test battery and the Trail Making Test A on average 13 years after baseline. Lifestyle measurements included annual clinical measurements, food records, and exercise questionnaires during both the intervention and follow-up phase. RESULTS: Lower intake of total fat (p=0.021) and saturated fatty acids (p=0.010), and frequent physical activity (p=0.040) during the whole study period were associated with better cognitive performance. Higher BMI (p=0.012) and waist circumference (p=0.012) were also associated with worse performance, but weight reduction prior to the cognition assessment predicted worse performance as well (decrease vs. increase, p=0.008 for BMI and p=0.002 for waist). CONCLUSIONS: Long-term dietary fat intake, BMI, and waist circumference have an inverse association with cognitive function in later life among people with IGT. However, decreases in BMI and waist prior to cognitive assessment are associated with worse cognitive performance, which could be explained by reverse causality.

Homocysteine and holotranscobalamin and the risk of Alzheimer disease: a longitudinal study.

OBJECTIVE: To examine the relation between serum levels of homocysteine (tHcy) and holotranscobalamin (holoTC), the active fraction of vitamin B12, and risk of incident Alzheimer disease (AD) in a sample of Finnish community-dwelling elderly. METHODS: A dementia-free sample of 271 subjects aged 65-79 years derived from the Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) study was followed up for 7 years to detect incident AD. The association between serum tHcy and holoTC with AD was analyzed with multiple logistic regression after adjusting for several potential confounders, including common vascular risk factors. RESULTS: The odds ratios (ORs) (95% confidence interval [CI]) for AD were 1.16 (1.04-1.31) per increase of 1 µmol/L of tHcy at baseline and 0.980 (0.965-0.995) for each increase of 1 pmol/L baseline holoTC. Adjustment for several potential confounders including age, sex, education, APOE ε4 allele, body mass index, Mini-Mental State Examination, smoking, stroke, and blood pressure did not alter the associations: ORs (95% CI) for AD became 1.19 (1.01-1.39) for tHcy and 0.977 (0.958-0.997) for holoTC. Adjusting for holoTC attenuated the tHcy-AD link (OR changed from 1.16 to 1.10, 95% CI 0.96-1.25). The holoTC-AD relationship was less influenced by controlling for tHcy (OR changed from 0.980 to 0.984, 95% CI 0.968-1.000). Addition of folate did not change any of the results. CONCLUSIONS: This study suggests that both tHcy and holoTC may be involved in the development of AD. The tHcy-AD link may be partly explained by serum holoTC. The role of holoTC in AD should be further investigated.

Diabetes, Alzheimer disease, and vascular dementia: a population-based neuropathologic study.

OBJECTIVE: To investigate the relation of diabetes to dementia, Alzheimer disease (AD), and vascular dementia (VaD), through analyses of incidence, mortality, and neuropathologic outcomes in a prospective population-based study of the oldest old. METHODS: The Vantaa 85+ study included 553 residents living in the city of Vantaa, Finland, and aged ≥85 years on April 1, 1991. Survivors were reexamined in 1994, 1996, 1999, and 2001. Autopsies were performed in 291 persons who died during the follow-up (48% of total population). Diabetes was assessed according to self-report, medical record of physician-diagnosed diabetes, or use of antidiabetic medication. Macroscopic infarcts were identified from 1-cm coronal slices of cerebral hemispheres, 5-mm transverse brainstem slices, and sagittal cerebellum slices. Methenamine silver staining was used for ß-amyloid, methenamine silver-Bodian staining for neurofibrillary tangles, and modified Bielschowsky method for neuritic plaques. Cox proportional hazards and multiple logistic regression models were used to analyze the association of diabetes with dementia and neuropathology, respectively. RESULTS: Diabetes at baseline doubled the incidence of dementia, AD, and VaD, and increased mortality. Individuals with diabetes were less likely to have ß-amyloid (hazard ratio [HR] [95% confidence interval (CI)] was 0.48 [0.23-0.98]) and tangles (HR [95% CI] 0.72 [0.39-1.33]) but more likely to have cerebral infarcts (HR [95% CI] 1.88 [1.06-3.34]) after all adjustments. CONCLUSION: Elderly patients with diabetes develop more extensive vascular pathology, which alone or together with AD-type pathology (particularly in APOE ε4 carriers) results in increased dementia risk.

Human herpesvirus-6 associated encephalitis with subsequent infantile spasms and cerebellar astrocytoma.

A 14-month-old girl presented after 3 days of fever, floppiness, and diffuse urticarial exanthem. She developed encephalitis and carditis and 1 week later, intractable seizures. Initial CT and MRI showed no changes in the brain parenchyma. On days 14 and 34 after the onset of symptoms, a human herpesvirus-6 (HHV-6) genome in cerebrospinal fluid was identified by polymerase chain reaction (PCR). Convulsions became more frequent and 11 weeks from the onset, they changed to typical infantile spasms with hypsarrhythmic electroencephalogram. She gradually lost her social contact and ability to walk and sit. Eleven months after the primary infection, a repeated MRI of the brain revealed a cystic tumour of 2 cm in diameter near the vermis. The tumour was surgically removed, and shown to be a pilocytic astrocytoma on histopathological examination. HHV-6 DNA was detected by PCR in new tumour tissue. This is the first reported case of HHV-6 encephalitis associated with carditis, infantile spasms, and a subsequent brain tumour containing the HHV-6 genome.

In situ hybridization detection of human herpesvirus 6 in brain tissue from fatal encephalitis.

A 23-month-old girl died after 2 days' illness with rash, fever, and convulsions. Neuropathologic findings were consistent with viral hemorrhagic encephalitis in pontine tegmentum and medial thalamic areas. Human herpesvirus 6 (HHV-6) DNA was detected in pontine nuclei by in situ hybridization. In addition, polymerase chain reaction for HHV-6 of serum and paraffin-embedded pontine tissue was positive, and serology indicated an acute primary infection. This is the first case showing HHV-6 DNA in the brain cells of an immunocompetent patient with acute encephalitis.