Longitudinal Effects of Herpesviruses on Multiple Cognitive Outcomes in Healthy Elderly Adults

• Background: Herpesviruses have been proposed to be involved in Alzheimer's disease development as potentially modifiable pathology triggers. Objective: To investigate associations of serum antibodies for herpes simplex virus (HSV)-1 and cytomegalovirus (CMV) and anti-herpesvirus treatment with cognitive outcomes in relation to interactions with APOE epsilon 4.Methods: The study included 849 participants in the population-based Prospective Investigation of the Vasculature in Uppsala Seniors study. Cognitive performance at the ages of 75 and 80 years was assessed using the Mini-Mental State Examination (MMSE), trail-making test (TMT) A and B, and 7-minute screening test (7MS).Results: Anti-HSV-1 IgG positivity was associated cross-sectionally with worse performance on the MMSE, TMT-A, TMT-B, 7MS, enhanced free recall, and verbal fluency tests (p = 0.016, p = 0.016, p < 0.001, p = 0.001, p = 0.033, and p < 0.001, respectively), but not orientation or clock drawing. Cognitive scores did not decline over time and longitudinal changes did not differ according to HSV-1 positivity. Anti-CMV IgG positivity was not associated cross-sectionally with cognition, but TMT-B scores declined more in anti-CMV IgG carriers. Anti-HSV-1 IgG interacted with APOE epsilon 4 in association with worse TMT-A and better enhanced cued recall. Anti-HSV IgM interacted with APOE epsilon 4 and anti-herpesvirus treatment in association with worse TMT-A and clock drawing, respectively.Conclusion: These findings indicate that HSV-1 is linked to poorer cognition in cognitively healthy elderly adults, including impairments in executive function, memory, and expressive language. Cognitive performance did not decline over time, nor was longitudinal decline associated with HSV-1.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Neurologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Neurology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Annan medicin och hälsovetenskap -- Gerontologi, medicinsk/hälsovetenskaplig inriktning (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Other Medical and Health Sciences -- Gerontology, specialising in Medical and Health Sciences (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Geriatrik (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Geriatrics (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)

Nyckelord

Aged 80 and over

Alzheimer's disease

Apolipoproteins E

cognition disorders

cohort studies

cytomegalovirus

dementia

Herpes simplex

herpesvirus 1 human

neurocognitive disorders

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