Welcome!

As a neuroscientist, I am interested in age-related neurodegenerative diseases including Alzheimer’s disease & associated disorders.
My research involves multimodal neuroimaging (structural and functional MRI, PET with multiple radiotracers) and neuropsychological tools, as complementary approaches are required to better characterize – and hopefully understand – these disorders. From a more fundamental perspective, studying the diseased brain will also contribute to further our knowledge on the neural basis of cognitive functions in the normal brain.

On this website, you will find information on my past, current, and futur research projects, scientific interests and collaborators.
You can also follow me on ResearchGate, Google Scholar, Pubmed and Twitter.

Do not hesitate to contact me for further questions: renaud.lajoie at gmail.com

Post publication analyses

Scientific investigations don’t have to (should not!) stop when a paper is accepted for publication in a peer-review journal. This is probably one of the main advantages of using social media in academia: they are places for sharing results and commenting them. There is no reason why peer-review should only happen before publication, so any feedback is welcome anytime! Let’s just make sure the critiques remain courteous and constructive so people don’t feel personally mocked or attacked. That could help avoid another ridiculous methodological terrorism debate and instead spend our time and energy improving our methods and approaches.

In line with this positive impact of social media to research quality, I posted on twitter early September after the above mentioned paper was accepted in Alzheimer’s and dementia. I got interesting feedback, comments and questions regarding some of our results, and notably the potential impact of outliers in some the analyses. In the attached document, you can find additional analyses and figures I conducted accordingly.

• Good point: these additional analyses all confirmed the original results.
• Bummer: the paper processing was too advanced for me to modify the final version of the article, so these (beautiful) figures and results will not be included in the final article.

SCD paper accepted in Alzheimer’s & Dementia

I am very proud and happy to announce that Alzheimer’s & Dementia: the Journal of the Alzheimer’s Association just accepted one of our papers for publication. This paper is the result of a great work conducted with dear friend and colleague Audrey Perrotin in the Inserm u1077 Chetelat lab in Caen! You can access the accepted manuscript here or look at the proofs on the journal website.

Subjective Cognitive Decline (SCD), an increasingly popular entity, refers to the presence of an isolated subjective/self-reported cognitive decline in older individuals without any abnormal clinical or neuropsychological examination. Although these individuals perform in the normal range on a bunch of standardized neuropsychological tests, they are still at risk of developing Alzheimer’s disease, and are currently being scrutinized by Azheimer’s researchers. The conceptual paper published by the SCD initiative in 2014 emphasized the interest of studying these individuals in the context of preclinical AD, but also emphasized that SCD was an umbrella term and that the aspects of SCD associated with early features of AD need refinement.

In this paper, we assessed cognitive, affective and neuroimaging (structural MRI and amyloid-PET) indices in 2 groups of cognitively normal older individuals classified as SCD according to different approaches: i) individuals who consulted at a memory clinic because of their subjective feeling of cognitive decline (SCD-clinic) and ii) individuals recruited from the community for our academic study of aging who scored high on a self-rated questionnaire of cognitive difficulties (SCD-community).

Both SCD groups were associated with a burden of neuroimaging biomarker abnormalities and subclinical affective symptomatology, but that these pattern varied according to the definition of SCD: anxiety and amyloid-plaques were statistically increased in both groups with SCD compared to a control group, while subclinical depression and brain atrophy were marked in the medical-help seeking group only.

These results further validate the concept of SCD in both community and clinic-based groups but also highlight the heterogeneous nature of SCD depending on study characteristics. These results has major impact on future studies in preclinical AD, notably in terms of enrichment for clinical trials.

This is an happy end for a long paper story. A preliminary version of the study was initially presented at the Alzheimer’s Association International Conference in Boston in 2013 (see abstract). We then included (many!) more participants in our study, and after a few unsuccessful submissions/modifications as well as additional analyses, the manuscript got accepted in a perfectly fitted journal.

You can access the accepted manuscript here or look at the proofs on the journal website.

Perrotin A*, La Joie R*, de La Sayette V, Barre L, Mezenge F, Mutlu J, Guilloteau D, Egret S, Eustache F, Chetelat G  (in press). Subjective cognitive decline in cognitively normal elders from the community or from a memory clinic: differential affective and imaging correlates. Alzheimer’s & Dementia: the Journal of the  Alzheimer’s Association.

Summer conferences

July was a crazy month! I attended a couple of very interesting but very different conferences that took place on 2 continents… within a few days!

I first flew to Budapest to attend ICOM6 (the 6th edition of the International Conference on Memory, see here) where I gave two talks. The first one was about imaging of hippocampal subfields in aging and Alzheimer’s disease, during which I also talked about our on going initiative for segmentation harmonization. The second one was about the comparison between Alzheimer’s disease and semantic dementia; I mentioned my previous work, as well as the follow up work by Alexandre Bejanin that in currently submitted for publication.

I then directly flew to Toronto to attend AAIC (Alzheimer’s Association International Conference, which I’ve attended 6 years in a row since the 2011 edition in Paris). I gave the opening plenary talk of the Alzheimer’s Imaging Consortium, the neuroimaging preconference. This presentation aimed at summarizing what we have learned in the last year, ie the hundreds of papers published in the field since last AAIC in Washington DC… Quite a program!
At AAIC, I also presented a poster on a quali-quantitative assessment of self-reported cognitive deficits. I really enjoyed conducting this original research (my first study without neuroimaging data!) and was happy to see that many other researchers were interested in the topic. Many exciting and fruitful discussions at the poster!

Now back to work at the Memory and Aging Center!

Photo credit: Left panel is derived from the ICOM website here.

Demented patients without amyloid?

In a paper published in Brain (available online ahead of print here), we specifically studied a series of demented patients with a clinical diagnosis of Alzheimer’s disease but who had a negative beta-amyloid PET scan. The paper includes cross sectional and longitudinal clinical data, as well as neuroimaging data from structural MRI and FDG-PET.

This publication, led by Gael Chetelat’s group in Caen, France, is the result of a great collaboration with three other world-famous groups:
– The group of Gil Rabinovici at UCSF (+Bill Jagust at UC Berkeley)
– The group led by Chris Rowe and Victor Villemagne in Melbourne
– The group led by Philip Scheltens in Amsterdam

Chételat G, Ossenkoppele R, Villemagne VL, Perrotin A, Landeau B, Mezenge F, Jagust WJ, Dore V, Miller BL, Egret S, Seeley WS, van der WM, La Joie R, Ames D, van Berckel BNM, Scheltens P, Barkhof F, Rowe CC, Masters CL, de La Sayette V, Bouwman F, Rabinovici GD (in press). Atrophy, hypometabolism and clinical trajectories in amyloid-negative Alzheimer’s disease patients. Brain

Back to Bay area & upcoming AAIC

I haven’t updated this for a while, probably because a lot has happened in the last few months:

• After months of administrative struggle to get my visa, I moved back to the bay area! I joined Gil Rabinovici’s lab at the Memory and Aging Center at UCSF. I am very enthusiatic to be part of one of the most exciting world-wide research centers in the  field of aging and neurodegenrative diseases. Lots of unique learning experiences and collaborations ahead of me.

• I was invited to give the opening plenary talk at the next Alzheimer’s Imaging Consortium (AIC), the imaging-centric preconference of the Alzheimer’s Association International Conference (AAIC) in Toronto, on July 23. This new type of presentation was initiated last year: a “junior” scientist has 30 min to present an overview of the research published since the last AAIC. Last year, Michel Grothe did a great job for the first edition of this special overview talk, and it seems that AIC organizers decided to make this a new “tradition”. Looking forward to Toronto!

Structural imaging of hippocampal subfields: our review of studies in ageing and Alzheimer’s disease

Neuroscience, the journal of the International Brain Research Organization (IBRO), will soon release a special issue entitled “Hippocampal vulnerability: from molecules to diseases“. Together with Robin de Flores & Gaël Chételat, we contributed to this issue with a review on MRI studies of hippocampal subfield structural changes in ageing and Alzheimer’s disease.

In a first section, we described the methodological aspects of subfield structural imaging and the technical evolutions over the last 15 years. We then described the major findings in normal ageing and different stages of Alzheimer’s disease (dementia, Mild Cognitive impairment, preclinical). Lastly, we summarized the results of studies reporting correlation between specific subfield(s) and memory scores assessing different subcomponents of memory.

Overall, this 218-reference review highlights the finding that in vivo neuromaging can capture the early differential vulnerability of hippocampal subfields in Alzheimer’s, and that subfield volumetry is more sensitive than classical whole hippocampal volumetry to AD-related changes. However, we also pointed a lot of inconsistent findings in aging and cognition-volume correlational studies. These contradictions are likely due to between-lab methodological differences, especially regarding subfiel definition on MRI data. This issue is currently under investigation by the hippocampal subfield group I am involved in.

de Flores R*, La Joie R*, Chételat G, (in press). Structural imaging of hippocampal subfields in healthy aging and Alzheimer’s disease. NEUROSCIENCE      [*: equal contribution]

Review of FDG-PET studies of memory impairment

In a paper to be published in a special issue of Neuropsychology Reviews, several members of the Inserm u1077 lab in Caen (including myself), give an overview of the 3-decade literature of FDG-PET studies of patients with memory deficits. The paper, which was led by Shail Segobin, a post doctoral fellow in the Inserm u1077 lab has three major sections:

1. ‘Fundamentals of PET‘, which explain the main principles of PET imaging: data acquisition and reconstruction, as well as partial volume effect and quantification issues. As a neuroimaging data specialist, Shail Segobin wrote this section, which could be a nice refresher for those who are not familiar with the underlying technique behind our nice 3D images!
2. ‘FDG-PET Investigations in non-Degenerative Pathologies‘. This section is an overview of FDG-PET findings is Alcohol-dependance, Korsakoff’s syndrome, transient amnesia, permanent organic amnesia and dissociative amnesia. Hélène Beaunieux, Anne-Lise Pitel, Ludivine Ritz, and Francis Eustache contributed to this section.
3. ‘FDG-PET Investigations in normal ageing and Neurodegenerative Diseases‘. Here, we described patterns of hypometabolism associated with ageing and associated neurodegenerative disorders, notably Alzheimer’s disease, but also dementia with Lewy body or Fronto-Temporal Dementias. Over and above simple description of FDG-PET abnormalities, we also summarized how they related to other brain alterations (atrophy or beta-amyloid deposition) or changes in cognition. This section was mainly contributed by Béatrice Desgranges, Gaël Chételat and I.

The review has several illustrations (including original figures, as well as 15 figures published in previous articles from our group and others) and above 200 references.

Segobin S, La Joie R, Ritz L, Beaunieux H, Desgranges B, Chételat G, Pitel AL, Eustache F (in press). FDG-PET contributions to the pathophysiology of memory impairment. NEUROPSYCHOLOGY REVIEWS

Summer papers

News papers just came up. Once more, they result from great collaborations with researchers from Caen (Inserm u1077, Gaël Chételat) and UC Berkeley/UCSF (Bill Jagust, Gil Rabinovici).

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Audrey Perrotin, PhD (Inserm u1077, Caen) focused on patients with Subjective Cognitive Decline (SCD), who seek help in a memory clinic but show no significant deficits on standard cognitive tests. Yet, these patients are at increased risk of  developing Alzheimer’s and they have recently become a population of high interest for research on preclinical AD  (see Jessen et al., 2014). In this study, Audrey looked at hippocampal subfield atrophy in 17 patients recruited from our local memory clinic, compared to 40 healthy controls (who never attended a memory clinic) and 21 patients at the dementia stage of AD. The main results of this study is that individuals with SCD already have an AD-like pattern of hippocampal atrophy (with major atropy of CA1 and the subiculum). This paper will soon be published in a special edition of the Journal of Alzheimer’s disease on SCD.

Perrotin A, de Flores R, Poisnel G, La Joie R, de la Sayette V, Mézenge F, Tomadesso C, Landeau B, Desgranges B, Chételat G (in press). Hippocampal subfield volumetry and 3D surface mapping in subjective cognitive decline. JOURNAL OF ALZHEIMER’S DISEASE

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In the second paper derived from my collaboration with Rik Ossenkoppele, PhD (UCSF), we studied early atrophy patterns in four clinical variants of AD (early onset, late onset, posterior cortical atrophy and logopenic aphasia). This paper included several complementary analyses of cognition and brain structure data, notably including the W-score map method I developed in a former paper (La Joie et al., J Neurosci 2012) and which Rik already used in a recent paper on “frontal” AD (Ossenkoppele et al., Brain 2015). Briefly, we showed that, even at the earliest clinical stage, patients with each syndrome showed both common and variant-specific atrophy. The paper is already available on the Human Brain Mapping Journal website.

Ossenkoppele R, Cohn-Sheehy BI, La Joie R, Vogel JW, Möller C, Lehmann M, van Berckel BNM, Seeley WW, Pijnenburg YA, Gorno-Tempini ML, Kramer JH, Barkhof F, Rosen HJ, van der Flier WM, Jagust WJ, Miller BL, Scheltens P, Rabinovici GD (in press). Atrophy Patterns in Early Clinical Stages Across Distinct Phenotypes of Alzheimer’s Disease. HUMAN BRAIN MAPPING

Recent media coverage

The recent papers mentioned below have drawn some media attention in the last week.

See the Alzforum article about the “Frontal variant Alzheimer’s disease” paper by Rik Ossenkopple et al (Brain 2015).

The article by Jacobsen et al (Brain 2015) also got attention from multiple websites: SciFeeds, Science News, Medical X Press, and the official website of the Max Planck Institute where our collaborators works.

Preclinical AD, Frontal AD, anosognosia in AD… New publications from fruitful collaborations!

Many good news came up these last few weeks. During my PhD in Caen (with Gaël Chételat) and post doc in Berkeley (with Bill Jagust), I had the opportunity to collaborate on multiple projects… that just led to three great publications on (very) different topics!

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Audrey Perrotin, PhD (Inserm u1077, Caen) our queen of meta-memory, studied the neural underpinnings of anosognosia in patients with AD at the dementia stage; after two rounds of thorough review and great responses, the paper finally got accepted in the Annals of Neurology. Her approach combines smart metrics to assess anosognosia (“delta score”) and multimodal imaging (FDG-PET and resting-state fMRI) to identify associated brain alterations. The article is available here.

Perrotin A, Desgranges B, Landeau B, Mézenge F, La Joie R, Egret S, Pélerin A, de la Sayette V, Eustache F, Chételat G (in press). Anosognosia in Alzheimer’s disease: disconnection between memory and self-related brain networks. ANNALS OF NEUROLOGY

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Florent Besson, MD (Inserm u1077, Caen) analyzed the data from cognitively intact elders and assessed their status regarding the three main AD neuroimaging biomarkers (MRI, FDG-PET and beta-amyloid-PET). He looked at cognitive and cerebral correlates of biomarker positivity. This paper was just accepted in The Journal Of Neuroscience.

Besson FL, La Joie R, Doeuvre L, Gaubert M, Mézenge F, Egret S, Landeau B, Barré L, Abbas A, de la Sayette V, Desgranges B, Eustache F, Chételat G (in press). Cognitive and brain profiles associated with each neuroimaging biomarker in preclinical Alzheimer’s disease. THE JOURNAL OF NEUROSCIENCE

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Rik Ossenkoppele, PhD (UCSF) did a great job combining MRI data from the memory and aging center in UCSF and the VU medical center in Amsterdam. He assessed the patterns of atrophy in patients who are commonly refered to as having “frontal AD” (with predominant behavioral and/or dysexecutive symptoms), and compared them to both typical AD and bvFTD (behavioral variant Fronto-Temporal Dementia). This huge paper includes clinical data, neuroimaging (MRI) and neuropathology. I was involved in the MRI data preprocessing and analyzing; with Jacob Vogel, we adapted the W-score map approach I developed in a former paper (La Joie et al., J Neurosci 2012) to the current sample to obtain 3D brain maps indicating which brain regions were frequently atrophied in each clinical group. The paper will soon be available in Brain.

Ossenkoppele R, Pijnenburg YAL, Perry DC, Cohn-Sheehy BI, Scheltens NME, Vogel JW, Kramer JH, van der Vlies AE, La Joie R, Rosen HJ, van der Flier WM, Grinberg LT, Rozemuller AJ, Huang EJ, van Berckel BNM, Miller BL, Barkhof F, Jagust WJ, Scheltens P, Seeley WW, Rabinovici GD (in press). Behavioral/Dysexecutive Variants of Alzheimer’s Disease: Clinical, Neuroimaging and Pathological Features.  BRAIN