Familial Alzheimer's Disease (FAD)

• Nick Fox
• Natalie Ryan
• Xin Zhang
• Moneeb Nasir
• Helen Rice
• Erinna Bowman
• Emily Goddard
• Phil Weston
• Joanna Ravenscroft
• Dilek Ocal
• Celine El Baou
• Ollie Hayes
• Emily Abel
• Suzie Barker
• Millie Beament

Overview

The DRC has been conducting a longitudinal study into Familial Alzheimer's Disease (FAD) for over thirty years. 

Since participants at risk of developing the disease are assessed prior to the onset of any symptoms, we are able to obtain valuable information on the earliest signs of the disease. 

Additionally, by tracking individuals over many years, we gain insight into how the disease progresses.

This work will improve our ability to diagnose the disease earlier, track disease progression, and assess any new potential biomarkers. 

What’s involved

Participants come to the DRC to complete neurological, imaging, and neuropsychological assessments. We collect samples and ask about family trees and general health and wellbeing. Activities typically take place on an annual basis. 

Who can take part

We see individuals from families affected by FAD as well as individuals with no known risk of AD and those with a diagnosis of mild cognitive impairment (MCI) or non-autosomal dominant (“typical”) Alzheimer’s Disease.

We remain incredibly grateful to all the participants who have so generously contributed to this research. 

If you are interested in learning more, please contact us at uclh.fad@nhs.net.

Overview

The DIAN Observational study is an international collaborative research project studying FAD. There are 14 centres worldwide, including one here at the DRC. The aim of the DIAN Observational study is to look at changes that occur in the brain in FAD even prior to the onset of any symptoms, and on a larger scale than has ever been possible before.

What’s involved

For this study, in-person research visits are completed every other year. These involve a number of activities which help us to look at FAD from a number of different perspectives, including neurological examinations, psychology assessments, and imaging. We also collect samples and complete a lumbar puncture. In the interval year, visits are typically a brief telephone call.

Who can take part

This study invites people who are at risk of FAD (have a parent with the condition, but do not know their own genetic status), those who know they are carriers of a FAD gene, and those with symptoms of FAD to take part. 

Click here to find out more about the DIAN Observational study.

DIAN-TU (Dominantly Inherited Alzheimer’s Disease/FAD – Trials Unit) is the clinical research arm of DIAN, and has just one research facility in the UK, based here at UCL. 

DIAN-TU’s primary goal is to implement effective, safe, and efficient clinical trials. Research within DIAN-TU is likely to advance a broader understanding of all types of Alzheimer’s disease with regards to causes, early detection, diagnosis, the effects of multiple classes of drugs, and the impact of treating Alzheimer’s disease early.

Click here to find out more about clinical trials at UCL.

Overview

The aim of the Fibroblast study is to investigate why brain cells generated from people living with Familial Alzheimer’s Disease behave differently to those from control participants to inform the development of future treatments.  

What’s involved

In this study we take a skin sample from the upper arm under a local anaesthetic.    

We use this skin sample to grow cell types from the skin (fibroblasts) in the laboratory. In a small petri dish, these cells are grown into stem cells and nerve resembling neurons in the brain.

Who can take part

This study invites people who know they carry the gene that causes FAD, those living with symptomatic FAD, and healthy volunteers (those not known to be at risk of FAD) to take part.

Click here to find out more Dementia Research – Brains in a Dish.

Audition biomarkers in dementia: Improving diagnosis and Tracking disease evolutION 

Overview

The AUDITION study is a sub-study of the 'Brain signatures of auditory information processing study'. The sub-study has generously been funded by a Fellowship award from the Alzheimer’s Society to Dr Chris Hardy.

Lots of research suggests that there is a relationship between hearing loss and dementia, but the nature of this relationship isn’t understood: does dementia cause hearing loss? Or does hearing loss cause dementia? Or is it more complicated than either of those? This is indeed a complex area: we of course hear with our ears, but also hear with our brains – and research has shown that the brain areas involved in performing difficult hearing tasks (like focusing on one person speaking in a noisy room) are the same brain areas that are affected very early in dementias like Alzheimer’s disease.

AUDITION aims to unpack this relationship by asking people with, or at risk of, Alzheimer’s disease to have a detailed hearing assessment. Results from AUDITION will allow us to start to answer questions about the order in which hearing symptoms emerge, and whether or not specific tests that we know target ‘brain hearing’ might even be helpful in detecting the earliest brain changes associated with Alzheimer’s disease.

What's involved

If you agree to take part we will ask for you to undergo a detailed assessment of your hearing, including standard pure-tone audiometry (which assess how well your ears can hear simple sounds); and other tasks assessing how your brain analyses complex sounds. You may be asked to wear headphones to listen to the sounds. We have adapted many of these tests for use remotely via the internet, so you would not necessarily have to travel to the research centre to participate in this study. The entire set of assessements takes around an hour to complete.

As an example of the kind of thing you will be asked to do:

1. We have artificially distorted this spoken sentence so that it sounds very strange - have a listen by clicking here:         

2. You probably found that impossible - but now see what happens if you click below to reveal the words to the sentence

3. Now if you listen to the sentence from Step 1 again, this should become a bit easier. This is because your brain has remarkably quickly adapted to the artificial solution.

Who can take part 

We are inviting the following people to participate in the sub-study:

• People who are at-risk of developing Alzeimer's Disease (AD) or Familial Frontotemporal Dementia (FTD) because a first-degree family member has a genetic form of either condition;
• People with a diagnosis of mild cognitive impairment; sporadic or FAD, sporadic or FTD, or related disorder. 

Please contact Dr Chris Hardy (chris.hardy@ucl.ac.uk) if you would like more information about the study or if you are interested in taking part.

Overview

We have recently launched a sub-study focusing on developing and using novel digital approaches to investigate and monitor early Alzheimer’s-related changes.  This sub-study does not require participants to come to a hospital or research centre for testing as activities can be undertaken when at home. There are 2 main aspects to the study:

1: Monitoring sleep patterns using a sleep mat

Aim: To understand how the quality of sleep is affected in the early stages of Alzheimer’s, and how this in turn affects the retention of new memories through the use of digital monitoring.

What’s involved

The participant places a sleep mat under their mattress to passively track sleep patterns, allowing continuous collection of data in their home environment. The mat sends data passively through Wi-Fi, enabling subtle early changes to be detected that might otherwise go unnoticed, without requiring participants to perform any specific tasks. The mat goes underneath the mattress and cannot be felt while the participant is in bed. 

2. Investigating long-term memory using a smartphone app

Aim: To use a smartphone‑based memory app capable of detecting very early changes in memory, with the goal of supporting earlier diagnosis and, in the future, identifying people for new treatments.

What’s involved

Participants will download a smartphone app and complete brief daily tasks over a 7‑day period, allowing researchers to assess how well new information is retained and consolidated across a longer timeframe than is possible in clinic. Each task lasts only a few minutes, providing a simple way to capture subtle changes in long‑term memory.

Who can take part

Anyone who is at risk of FAD, or is a known gene mutation carrier and is either asymptomatic or mildly affected, may take part. Anyone interested in this, or who would like further information, should please contact Dr Phil Weston (philip.weston@ucl.ac.uk), or Joanna Ravenscroft (joanna.ravenscroft1@nhs.net).

Detecting cerebral amyloid angiopathy in familial Alzheimer’s disease - to reduce the risks of amyloid immunotherapy

Overview

This is a sub-study of our Longitudinal study of familial Alzheimer’s disease (FAD). The purpose of the Longitudinal study of FAD is to identify the earliest changes associated with the development and progression of AD pathology. In AD, a protein called amyloid-beta builds up in brain tissue as plaques and can also be deposited in blood vessel walls – this is called cerebral amyloid angiopathy (CAA). CAA severity varies widely between different people with AD and this can be a factor influencing the risk of developing side-effects with new treatments using amyloid-beta immunotherapy. The purpose of this sub-study is to develop more sensitive markers of CAA in AD by assessing measures of functional activity in the brain and in the brain’s blood vessels, determined using functional MRI (fMRI) and magnetoencephalopgraphy (MEG) scans.

The fMRI sequence lets us look at changes in blood flow that occur in visual areas of the brain following presentation of visual stimuli. The MEG allows us to study changes in the magnetic field surrounding the brain, which occur following electrical activity in the neurons. 

What's involved

You will be asked to sit upright in a comfortable chair in the MEG scanner for the duration of the MEG scan (up to 30 minutes). During the scan you will see flashing black and white chequerboard patterns on a computer screen, and from time to time you will be asked to press buttons on a keypad. You will also be scanned whilst resting, before and after doing this task. 

You will then be asked to do the same task (pressing buttons while chequerboard pattern images are presented on a screen) during an MRI brain scan, for which you will be lying down on a scanning bed. This type of MRI sequence, called functional MRI (fMRI), will be carried out during the MRI brain scanning session that you have for your participation in the Longitudinal Study of FAD. The total MRI scan time will be up to one hour. 

For your comfort, you will have a break between the MEG and MRI scans when you can have a drink of water and use the bathroom if you wish. 

Who can take part

We are currently recruiting people at risk of developing FAD and people who are in the early symptomatic stage of FAD. 

Overview

This study aimed to further our understanding of the earliest changes in brain structure in Alzheimer’s disease. MRI uses magnetic fields to generate pictures of the brain and measure different changes. This project used a new type of scanner with a higher MRI magnet strength than standard scanners – known as “ultra-high field MRI” or “7 Tesla MRI” – to provide more precise and detailed information. The higher level of magnification provided allows us to explore specific changes in a way not previously possible.

What was involved

Similar to other MRI scans, participants lay down with their head held still, with the scan lasting around an hour in total.

Who participated

Anyone involved in our main Longitudinal FAD study was welcome to indicate interest in taking part. 

The data from the ultra-high field MRI scans are currently being processed and analyses with results from the study expected soon.

For further information, please contact Dr Phil Weston (philip.weston@ucl.ac.uk).

Overview

The purpose of the MEG sub-study of our Longitudinal Study of FAD was to measure directly brain activity in real-time to find biomarkers accurately reflecting early changes in brain function in Alzheimer’s disease and to relate those changes to symptoms. 

To do this, we performed MEG scans to study unique patterns of magnetic waves made by the brain cells of participants while they were performing different mental activities, e.g. viewing pictures, doing a memory game, and/or resting. 

MEG scans are very safe as they are non-invasive, quiet, and do not produce radiation. Participants sit upright and interact with a computer during the scan. 

What was involved 

Participants were invited for a two-day visit.

On day 1, there was a computer-based practice session (1 hour). On day 2, there was a MEG scanning session with the participant performing the same activity they practiced on the previous day, but this time while seated in the MEG scanner (total of 1.5 hours, including 30 minutes for preparation, 45 minutes for the MEG scan, and 15 minutes for a debrief). 

For participant comfort, the 45-minute scan was broken into 6-7-minute blocks. 

We invited participants to return for a second two-day visit approximately 12 months after the initial scan, until study closure. 

Who participated

We recruited families affected by FAD, patients with mild cognitive impairment (MCI) due to sporadic (non-familial) Alzheimer’s disease, and those without any known connection to FAD or MCI (“healthy volunteers”).