Genetic Risk for Alzheimer’s Disease Moderates the Association Between Medial Temporal Lobe Volume and Episodic Memory Performance Among Older Adults

Abstract Epilepsy incidence and prevalence peaks in older adults yet systematic studies of brain ageing and cognition in older adults with epilepsy remain limited. Here, we characterize patterns of cortical atrophy and cognitive impairment in 73 older adults with temporal lobe epilepsy (>55 years) and compare these patterns to those observed in 70 healthy controls and 79 patients with amnestic mild cognitive impairment, the prodromal stage of Alzheimer’s disease. Patients with temporal lobe epilepsy were recruited from four tertiary epilepsy surgical centres; amnestic mild cognitive impairment and control subjects were obtained from the Alzheimer’s Disease Neuroimaging Initiative database. Whole brain and region of interest analyses were conducted between patient groups and controls, as well as between temporal lobe epilepsy patients with early-onset (age of onset <50 years) and late-onset (>50 years) seizures. Older adults with temporal lobe epilepsy demonstrated a similar pattern and magnitude of medial temporal lobe atrophy to amnestic mild cognitive impairment. Region of interest analyses revealed pronounced medial temporal lobe thinning in both patient groups in bilateral entorhinal, temporal pole, and fusiform regions (all P < 0.05). Patients with temporal lobe epilepsy demonstrated thinner left entorhinal cortex compared to amnestic mild cognitive impairment (P = 0.02). Patients with late-onset temporal lobe epilepsy had a more consistent pattern of cortical thinning than patients with early-onset epilepsy, demonstrating decreased cortical thickness extending into the bilateral fusiform (both P < 0.01). Both temporal lobe epilepsy and amnestic mild cognitive impairment groups showed significant memory and language impairment relative to healthy control subjects. However, despite similar performances in language and memory encoding, patients with amnestic mild cognitive impairment demonstrated poorer delayed memory performances relative to both early and late-onset temporal lobe epilepsy. Medial temporal lobe atrophy and cognitive impairment overlap between older adults with temporal lobe epilepsy and amnestic mild cognitive impairment highlights the risks of growing old with epilepsy. Concerns regarding accelerated ageing and Alzheimer’s disease co-morbidity in older adults with temporal lobe epilepsy suggests an urgent need for translational research aimed at identifying common mechanisms and/or targeting symptoms shared across a broad neurological disease spectrum.

Download Full-text

APOE4 status is related to differences in memory-related brain function in asymptomatic older adults: Baseline analysis of the PREVENT-AD task fMRI dataset

10.1101/2019.12.11.871681 ◽

2019 ◽

Author(s):

Sheida Rabipour ◽

Sricharana Rajagopal ◽

Elsa Yu ◽

Stamatoula Pasvanis ◽

John Breitner ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Older Adults ◽

Alzheimer's Disease ◽

Episodic Memory ◽

Brain Activity ◽

Memory Performance ◽

Group Differences ◽

Parental History ◽

History Of ◽

Spatial Source

AbstractEpisodic memory decline is one of the earliest symptoms of late-onset Alzheimer’s Disease (AD) and older adults with the apolipoprotein E e4 (+APOE4) genetic risk factor for AD may exhibit altered patterns of memory-related brain activity years prior to initial symptom onset. In the current study we report the baseline episodic memory task fMRI results from the PRe-symptomatic EValuation of Experimental or Novel Treatments for Alzheimer’s Disease (PREVENT-AD) study in Montreal, Canada, in which 327 healthy older adults, within 15 years of the parent’s conversion to AD, were scanned. During the task fMRI protocol volunteers were scanned as they encoded and retrieved object-location spatial source associations. The task was designed to discriminate between brain activity related to successful spatial source recollection and failures in spatial source recollection, with memory for only item (object) memory. Multivariate task-related partial least squares (task PLS) was used to test the hypothesis that +APOE4 adults with a family history of AD would exhibit altered patterns of brain activity in the recollection-related memory network, comprised of medial frontal, parietal and medial temporal cortices, compared to APOE4 non-carriers (-APOE4). We also tested for group differences in the correlation between event-related brain activity and memory performance in +APOE4 compared to -APOE4 adults using behavioral-PLS (B-PLS). We found group similarities in memory performance and in task-related brain activity in the recollection network. However, the B-PLS results indicated there were group differences in brain activity-behavior correlations in ventral occipito-temporal, medial temporal, and medial prefrontal cortices during episodic encoding. These findings are consistent with previous literature on the influence of APOE4 on brain activity and provide new perspective on potential gene-based differences in brain-behavior relationships in people with parental history of AD. Future research should further investigate the potential to distinguish risk of AD development based on memory performance and associated patterns of brain activity.

Download Full-text

Relationships Between Tau and Glucose Metabolism Reflect Alzheimer’s Disease Pathology in Cognitively Normal Older Adults

Cerebral Cortex ◽

10.1093/cercor/bhy078 ◽

2018 ◽

Vol 29 (5) ◽

pp. 1997-2009 ◽

Cited By ~ 19

Author(s):

Jenna N Adams ◽

Samuel N Lockhart ◽

Lexin Li ◽

William J Jagust

Keyword(s):

Alzheimer’S Disease ◽

Older Adults ◽

Alzheimer's Disease ◽

Glucose Metabolism ◽

Temporal Lobe ◽

Medial Temporal Lobe ◽

Amyloid Β ◽

Normal Aging ◽

Cognitively Normal ◽

Canonical Correlations

Abstract Tau is associated with hypometabolism in patients with Alzheimer’s disease. In normal aging, the association between tau and glucose metabolism is not fully characterized. We used [18F] AV-1451, [18F] Fluorodeoxyglucose, and [11C] Pittsburgh Compound-B (PiB) PET to measure associations between tau and glucose metabolism in cognitively normal older adults (N = 49). Participants were divided into amyloid-negative (PiB–, n = 28) and amyloid-positive (PiB+, n = 21) groups to determine effects of amyloid-β. We assessed both local and across-brain regional tau–glucose metabolism associations separately in PiB–/PiB+ groups using correlation matrices and sparse canonical correlations. Relationships between tau and glucose metabolism differed by amyloid status, and were primarily spatially distinct. In PiB– subjects, tau was associated with broad regions of increased glucose metabolism. In PiB+ subjects, medial temporal lobe tau was associated with widespread hypometabolism, while tau outside of the medial temporal lobe was associated with decreased and increased glucose metabolism. We further found that regions with earlier tau spread were associated with stronger negative correlations with glucose metabolism. Our findings indicate that in normal aging, low levels of tau are associated with a phase of increased metabolism, while high levels of tau in the presence of amyloid-β are associated with hypometabolism at downstream sites.

Download Full-text

Impact of Comorbid Depression on Serial Position Effects in Alzheimer’s Disease

GeroPsych ◽

10.1024/1662-9647/a000115 ◽

2014 ◽

Vol 27 (4) ◽

pp. 161-169 ◽

Cited By ~ 1

Author(s):

Nienke A. Hofrichter ◽

Sandra Dick ◽

Thomas G. Riemer ◽

Carsten Schleussner ◽

Monique Goerke ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Serial Position ◽

Episodic Memory ◽

Memory Performance ◽

Memory Function ◽

Word List ◽

Position Effects ◽

Serial Position Effects ◽

List Memory

Hippocampal dysfunction and deficits in episodic memory have been reported for both Alzheimer’s disease (AD) and major depressive disorder (MDD). Primacy performance has been associated with hippocampus-dependent episodic memory, while recency may reflect working memory performance. In this study, serial position profiles were examined in a total of 73 patients with MDD, AD, both AD and MDD, and healthy controls (HC) by means of CERAD-NP word list memory. Primacy performance was most impaired in AD with comorbid MDD, followed by AD, MDD, and HC. Recency performance, on the other hand, was comparable across groups. These findings indicate that primacy in AD is impaired in the presence of comorbid MDD, suggesting additive performance decrements in this specific episodic memory function.

Download Full-text