No abstract

The molecular and cellular mechanisms responsible for the etiology and pathogenesis of Alzheimer's disease (AD) have not been defined; however, inflammation within the brain is thought to play a pivotal role. Studies suggest that peripheral infection/inflammation might affect the inflammatory state of the central nervous system. Chronic periodontitis is a prevalent peripheral infection that is associated with gram-negative anaerobic bacteria and the elevation of serum inflammatory markers including C-reactive protein. Recently, chronic periodontitis has been associated with several systemic diseases including AD. In this article we review the pathogenesis of chronic periodontitis and the role of inflammation in AD. In addition, we propose several potential mechanisms through which chronic periodontitis can possibly contribute to the clinical onset and progression of AD. Because chronic periodontitis is a treatable infection, it might be a readily modifiable risk factor for AD.

Having a parent affected with late-onset Alzheimer's disease (AD) is a risk factor for developing AD among cognitively normal subjects. We examined whether cognitively normal subjects with a parental family history of AD show cerebral metabolic rate of glucose (CMRglc) reductions consistent with AD as compared with those without a family history and whether there are parent gender effects. Fortynine 50-to 80-year-old normal subjects were examined who received clinical, neuropsychological, and 2-[ 18 F]fluoro-2-deoxy-D-glucosepositron emission tomography examinations, including 16 subjects with a maternal (FHm) and eight with a paternal (FHp) family history of AD and 25 with no family history (FH ؊ ). FH groups were comparable for demographic and neuropsychological measures. As compared with both FH ؊ and FHp groups, FHm subjects showed CMRglc reductions in the same regions as clinically affected AD patients, involving the posterior cingulate cortex/precuneus, parietotemporal and frontal cortices, and medial temporal lobes (P < 0.05, corrected for multiple comparisons). These effects remained significant after accounting for possible risk factors for AD, including age, gender, education, apolipoprotein E genotype, and subjective memory complaints. No CMRglc differences were found between FHp and FH ؊ subjects. This study shows a relationship between reduced CMRglc in AD-vulnerable brain regions and a maternal family history of AD in cognitively normal individuals.A fter advanced age, the most significant risk factor for late-onset Alzheimer's disease (AD) is a family history of AD (1). Normal individuals with a first-degree relative affected by AD, especially a parent, are at a 4-to 10-fold higher risk for developing AD as compared with individuals with a negative family history (2-4). Apart from the rare early-onset form of familial AD related to autosomal dominant genetic mutations, genes with a clear Mendelian pattern of transmission for lateonset familial AD have not been identified. To date, the 4 allele of the apolipoprotein E (ApoE) gene is the only established genetic risk factor for late-onset AD and is found in Ϸ40% of late-onset AD cases with a positive family history (1). The ApoE-4 genotype has, however, no clear familial pattern of transmission and appears to act as a risk modifier by lowering the age at onset of clinical symptoms, rather than as a genetic determinant (see ref. 5 for review), indicating that other factors contribute to the etiology and phenotypic expression of disease. The biological mechanisms through which family history of AD confers increased susceptibility to late-onset AD are not known.A consistent feature of AD is the marked reduction of the cerebral metabolic rate of glucose (CMRglc) as measured by using positron emission tomography (PET) imaging with 2-[ 18 F]fluoro-2-deoxy-D-glucose (FDG) as the tracer (FDG-PET). FDG-PET studies demonstrate a specific pattern of CMRglc impairment in AD, involving the parietotemporal, posterior cingulate, and to a lesser extent frontal cort...

The associations of inflammation/immune responses with clinical presentations of Alzheimer’s disease (AD) remain unclear. We hypothesized that TNF-α and elevated antibodies to periodontal bacteria would be greater in AD compared to normal controls (NL) and their combination would aid clinical diagnosis of AD. Plasma TNF-α and antibodies against periodontal bacteria were elevated in AD patients compared with NL and independently associated with AD. The number of positive IgG to periodontal bacteria incremented the TNF-α classification of clinical AD and NL. This study shows that TNF-α and elevated numbers of antibodies against periodontal bacteria associate with AD and contribute to the AD diagnosis.

Background-We examined whether cerebral metabolic rates for glucose (CMRglc) on 2-[ 18 F] fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET) and cerebrospinal fluid (CSF) markers of Alzheimer's disease (AD) are altered in cognitively normal apolipoprotein E (ApoE) E4 carriers with subjective memory complaints (SMC).

Background:At cross-section, cognitively normal individuals (NL) with a maternal history of late-

P-tau(231) is the strongest predictor of the decline from MCI to AD. IP levels uniquely show longitudinal progression effects. These results suggest the use of CSF biomarkers in secondary prevention trials.

Background/Aims: Subjective memory complaint (SMC) in normal individuals may predict future cognitive decline. The goal of this study was to examine whether the probability of decline increases with growing intensity of complaint. Methods: Normal subjects over the age of 50 years were included in a longitudinal retrospective study (mean follow-up time = 8 years). All subjects (n = 230) underwent cognitive and medical examination at baseline. The presence of SMC was determined based on Global Deterioration Scale staging. A subgroup of 83 participants also received baseline assessment for the intensity of SMC. Logistic regression was used to predict outcome from baseline variables. Three outcome groups were established at the final visit: nondeclining, declining and diagnostically unstable (i.e. the diagnosis changed over time: from normal to mild cognitive impairment, then back to normal). Results: The presence of SMC was a predictor of future decline but also increased the likelihood of the unstable diagnosis. Increasing intensity of SMC did not further raise the risk for decline. High intensity of complaints and more pronounced affective symptoms predicted the unstable clinical diagnosis. Conclusions: The presence of SMC contributes to the risk of future decline, however, the increasing intensity of the perceived impairment does not further enhance the risk.