ClinicSpeak: creating brain reserve

Brain reserve: maximise and protect it. #ClinicSpeak #MSBlog #MSResearch

“A mainstream hypothesis circulating in the MS and dementia community is that brain reserve protects you from presenting with overt cognitive impairment or clinical dementia. The study below suggests that environmental enrichment (brain training) increases the size of the hippocampus in the brain and this is what protects you. The hippocampus is a specialised part of the brain that is involved in memory. Cognitive or brain reserve is not unique to memory; we think it plays a role in progressive MS as well.”

“It has become clear that anti-inflammatory therapies that prevent focal lesions developing in MS (relapses and MRI lesions) are not effective in slowing down the gradual acquisition of disability that characterises the so called non-relapsing progressive phase of MS (SPMS and PPMS). Why? I have hypothesised that the clinically-apparent progressive phase of MS is driven by mechanisms that are dependent on the length of the nerves involved and the ability of the specific pathways to recover and maintain function. The latter is called functional reserve; a more general term that includes brain reserve.  I have referred to this hypothesis in previous posts as the  asynchronous progressive MS hypothesis (APMSH).

“A potential implication of this hypothesis is that if one neuronal system is progressing clinically, for example lower limb motor function, it does not mean that other shorter neuronal systems (arms, swallowing, vision, etc.) are destined to become progressive if targeted with disease-modifying therapies. This hypothesis may explain why trials of disease modifying drugs in progressive MSers have been negative to date and also predicts therapeutic lag. If we can prove this hypothesis is correct it will have major implications for the design of future trials in progressive MS. What are we doing about it? We have put a consortium of investigators together and have applied to the PMSA (Progressive MS Alliance) for funding to investigate this hypothesis in more detail. We hope that we will be successful with our grant application.”

“In the mean time I think you should try and optimise your reserve capacity; the best way to do this is via our brain health initiative.”

Epub: Sumowski et al. Searching for the neural basis of reserve against memory decline: intellectual enrichment linked to larger hippocampal volume in multiple sclerosis. Eur J Neurol. 2015 Feb 4. doi: 10.1111/ene.12662.

BACKGROUND AND PURPOSE: Active engagement in intellectually enriching activities (e.g. reading, hobbies) builds ‘reserve’ against memory decline in elders and MSers, but the neural basis for this protective influence of enrichment is unknown. Herein the neuroanatomical basis of reserve against memory decline in MSers is investigated.

METHODS: Relapse-onset MSers (N = 187) underwent 3.0 T magnetic resonance imaging of the brain to quantify T2 lesion volume (T2LV) and normalized volumes of total brain, total white, total grey (using SIENAX) and thalamus, caudate, putamen, pallidum, amygdala and hippocampus (using FIRST). MSers completed a survey quantifying their engagement in early life intellectual enrichment (i.e. reading, hobbies). Verbal and visuospatial episodic memory was assessed with neuropsychological tasks in a representative subsample (N = 97).

RESULTS: Controlling for demographics and T2LV, intellectual enrichment was specifically linked to larger normalized hippocampal volume (rp = 0.213, P = 0.004), with no link to other brain volumes/structures. Moreover, greater intellectual enrichment moderated/attenuated the negative relationship between normalized total brain volume (i.e. overall cerebral atrophy) and normalized hippocampal volume (i.e. hippocampal atrophy; P = 0.001) whereby MSers who engaged in more early life intellectual enrichment better maintained hippocampal volume in the face of worse overall cerebral atrophy. Finally, the link between greater intellectual enrichment and better memory was partially mediated through larger hippocampal volume.

CONCLUSIONS: These findings support larger hippocampal volume as one key component of the neuroanatomical basis of reserve against memory decline in MS. These findings are consistent with previous literature on experience-dependent neuroplasticity within the hippocampus.

About the author

Prof G

Professor of Neurology, Barts & The London. MS & Preventive Neurology thinker, blogger, runner, vegetable gardener, husband, father, cook and wine & food lover.


  • Interesting post .So according to your APMSH and to your therapeutic lag theory , PPMS ( with no enhancing lesions) could benefit from highly effective DMT like Rituximab if prescribed early in the disease course?
    And is your APMSH and therapeutic lag theory a valid one for HSCT ?

    • Re: "….APMSH and therapeutic lag theory a valid one for HSCT ?"

      Yes, if the hypothesis is correct it will hold up for all DMTs. We need to test the hypothesis; we have not proven it.

  • This makes me so grateful for my education and past professional life. But now I'm retired, I find that intellectual stimulation can get in the way of sleep hygiene! Apart from daily sudokus and cryptic crosswords, I have a weekly crossword session with a friend (c. 7 hours). It involves so much puzzling, cross-referencing and general brain-stretching that I never get much sleep that night. Love it – and at least I can sleep in the next day!

  • [The onset of lower-limb MS progression] does not mean that other shorter neuronal systems (arms, swallowing, vision, etc.) are destined to become progressive if targeted with disease-modifying therapies."

    So if a PPMSer is given, say Mitoxantrone, two or three years into their MS symptoms, do you actually think that will be of service to the patient? Why? What are your scientific reasons for such a theory?

  • From your post on maintaining brain health: Review what drugs your are on; many of the drugs we prescribe to treat the symptoms of MS make cognitive impairment worse.
    Would you please elaborate on which drugs make cognitive impairment worse, please?

By Prof G



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