Self-Reported Late-Life Hypertension Is Associated with a Healthy Cognitive Status and Reduced Alzheimer's Disease Pathology Burden.

Background: While mid-life hypertension represents a risk factor for the development of Alzheimer's disease (AD), the risk after the age of 65 is less certain. Establishing relationships between late life hypertension and the pathological changes of AD could be crucial in understanding the relevance of blood pressure as a risk factor for this disorder. Objective: We investigated associations between self-reported late-life hypertension, cognitive status and AD pathology at death. The impact of antihypertensive medication was also examined. Methods: Using the Cornell Medical Index questionnaire, we ascertained whether participants had ever reported hypertension. We also noted use of antihypertensive medication. The donated brains of 108 individuals were assessed for AD pathology using consensus guidelines. Statistical analysis aimed to elucidate relationships between hypertension and AD pathology. Results: We found no associations between self-reported hypertension and cognitive impairment at death. However, those with hypertension were significantly more likely to exhibit lower levels of AD pathology as measured by Thal phase, Braak stage, CERAD score, and NIA-AA criteria-even after controlling for sex, level of education and presence of APOEɛ4 allele(s). No significant associations could be found when examining use of antihypertensive medications. Conclusions: Our findings suggest that late-life hypertension is associated with less severe AD pathology. We postulate that AD pathology may be promoted by reduced cerebral blood flow.

Telephone Interview for Cognitive Status Scores Associate with Cognitive Impairment and Alzheimer's Disease Pathology at Death.

BACKGROUND: Early diagnosis of Alzheimer's disease (AD) provides an opportunity for early intervention. Cognitive testing has proven to be a reliable way to identify individuals who may be at risk of AD. The Telephone Assessment for Cognitive Screening (TICS) is proficient in screening for cognitive impairment. However, its ability to identify those at risk of developing AD pathology is unknown. OBJECTIVE: We aim to investigate associations between TICS scores, collected over a period of 13 years, and the cognitive status of participants at death. We also examine relationships between TICS scores and neuropathological indices of AD (CERAD score, Thal phase, and Braak stage). METHODS: Between 2004 and 2017, participants from The University of Manchester Longitudinal Study of Cognition in Normal Healthy Old Age underwent cognitive assessment using TICS. Scores from four time points were available for analysis. Cognitive impairment and AD pathology at death was evaluated in 101 participants. RESULTS: TICS scores at time points 2, 3, and 4 were significantly lower in those cognitively impaired at death compared to those considered cognitively normal. There were significant negative correlations between TICS scores and CERAD score and Braak stage at time points 2 and 4. No correlations between Thal phase and TICS were found. CONCLUSION: Findings indicate that TICS could be used not only to screen for cognitive impairment, but also to identify individuals at risk of developing AD pathology, many years before any overt symptoms occur. Once identified, 'at risk' individuals could be targeted for early interventions which could attenuate the progression of the disease.

Influence of APOE genotype in primary age-related tauopathy.

The term "Primary age-related tauopathy" (PART) was coined in 2014 to describe the common neuropathological observation of neurofibrillary tangles without associated beta-amyloid (Aß) pathology. It is possible for PART pathology to be present in both cognitively normal and cognitively impaired individuals. Genetically, Apolipoprotein E (APOE) ε4 has been shown to occur less commonly in PART than in Alzheimer's disease (AD). Here, we investigate the relationships between PART, AD and those pathologically normal for age, with an emphasis on APOE and cognition, using 152 selected participants from The University of Manchester Longitudinal Study of Cognition in Normal Healthy Old Age and the Manchester arm of the Brains for Dementia Research cohort. APOE genotype differed between PART and AD with APOE ε2 more common in the former and APOE ε4 more common in the latter. Individuals with definite PART were less likely to be cognitively impaired than those with AD and those with pathology considered pathologically normal for age. We postulate that the lack of Aß in definite PART cases may be due either to an increased frequency of APOE ε2 or decreased frequency of APOE ε4 as their resulting protein isoforms have differing binding properties in relation to Aß. Similarly, an increased frequency of APOE ε2 or decreased frequency of APOE ε4 may lead to decreased levels of cognitive impairment, which raises questions regarding the impact of Aß pathology on overall cognition in elderly subjects. We suggest that it may be possible to use the increased frequency of APOE ε2 in definite PART to assist neuropathological diagnosis.

Influence of APOE Genotype on Mortality and Cognitive Impairment.

While many studies have examined the associations between APOE genotype and mortality, findings have often been conflicting and it remains unclear whether APOE genotype affects longevity. Using selected individuals from the Manchester arm of the Brains for Dementia Research programme and University of Manchester Longitudinal Study of Cognition in Normal Healthy Old Age, we investigated relationships between APOE genotype and age at death in both cognitively normal and cognitively impaired individuals. Results indicated that carrying the APOE ɛ4 allele led to a reduced chance in an individual reaching 80+ years and remaining cognitively healthy. Conversely, APOE ɛ2 carriers tended to live longer and remain cognitively normal. These findings add to the evidence that APOE genotype influences longevity, especially in cognitively impaired individuals who carry the APOE ɛ4 allele.