STUDY: Cognitive reserve and cortical atrophy in MS: A longitudinal study

[ActiveMSers]

The big takeaway from this study: "The time window of opportunity for therapeutic approaches aimed at intellectual enhancement most likely lies in the earliest disease stages." Exercise and disease-modifying treatment are known to prevent brain atrophy. Don't delay. - Dave


Neurology. 2013 Apr 10. [Epub ahead of print]

Cognitive reserve and cortical atrophy in multiple sclerosis: A longitudinal
study.

Amato MP, Razzolini L, Goretti B, Stromillo ML, Rossi F, Giorgio A, Hakiki B,
Giannini M, Pastò L, Portaccio E, De Stefano N.

From the Department of Neurology (M.P.A., L.R., B.G., B.H., M.G., L.P., E.P.),
University of Florence; Don Gnocchi Foundation (L.R., B.H., E.P.), Florence; and
Department of Neurological and Behavioural Sciences (M.L.S., F.R., A.G., N.D.S.),
University of Siena, Italy.

OBJECTIVE: To test the cognitive reserve (CR) hypothesis in the model of multiple
sclerosis (MS) by assessing the interactions among CR, brain atrophy, and
cognitive efficiency in patients with relapsing-remitting MS.

METHODS: A
Cognitive Reserve Index was calculated including education, premorbid leisure
activities, and IQ. Brain atrophy was assessed through magnetic resonance
quantitative parameters of normalized total brain volume and normalized cortical
volume. Cognitive function was measured using Rao's Brief Repeatable Battery.

RESULTS: Fifty-two patients with relapsing-remitting MS were evaluated at
baseline and 35 of them were reassessed after a 1.6-year follow-up period. At
baseline, higher CR predicted better performance on most of the Brief Repeatable
Battery tests, independent of brain atrophy and clinical and demographic
characteristics (p ≤ 0.021). An interaction between CRI and normalized cortical
volume predicted better cognitive performance on tasks of verbal memory and
attention/information processing speed (p < 0.005). However, at the follow-up
examination, progressing cortical atrophy (β = 0.45; p = 0.008) and older age (β
= -0.33; p = 0.044) were the only predictors of deteriorating cognitive
performance.

CONCLUSIONS: Our findings suggest that higher CR in individuals with
MS may mediate between cognitive performance and brain pathology. CR-related
compensation may, however, fail with progression of damage. The time window of
opportunity for therapeutic approaches aimed at intellectual enhancement most
likely lies in the earliest disease stages.

[Niko]

Did they compare their finds with average non-MSers? How fast does cognition deteriorate with them over time? What about the difference between MSers who take DMDs versus those who don't? What about people with MS who take other forms of therapy for cognition, like regular concentrated use of gingko biloba?

I'm not comfortable with the recommendation to take a DMD to slow cognitive deterioration if I don't know what to compare the results to, know what I mean?

[AMFADVENTURES]

Did they compare their finds with average non-MSers? How fast does cognition deteriorate with them over time? What about the difference between MSers who take DMDs versus those who don't? What about people with MS who take other forms of therapy for cognition, like regular concentrated use of gingko biloba?

I'm not comfortable with the recommendation to take a DMD to slow cognitive deterioration if I don't know what to compare the results to, know what I mean?

I don't blame you Niko, but I just returned from a presentation on exactly this subject. The studies concerning cognitive decline in MS vs non MS and with age are out there, cognitive decline is worse in PWMS and worse yet as PWMS age. If I ever come across a good bibliography I'll point you to it. As far as cognitive decline and DMT's, you might be right, there may not be a lot of information yet, but you should keep your eyes open at least according to the presentation I saw today because it seems to be a more recent development in research particularly as relates to the latest generation of drugs, Tysabri, Rituximab, Gylenia, and Tecifedera. Some of these drugs may be more immunoregulatory than immunosuppressive and may exhibit neuroprotective properties. Big differences from earlier drugs if it proves true.

The AAN had some pertinent studies in this area too, so if you've got a couple of days, you can look through the abstracts at http://www.abstracts2view.com/aan/

And if you've got a couple of weeks, look through some of the references mentioned, mostly by the presenters, in this twitter feed from the AAN, https://twitter.com/search?q=%23gssixp particularly references from the NIH as they are less influenced by big pharma.

If the studies you're looking for aren't there now, I suspect they will be over the next few years. All indications are that you are in a good position to lead a relatively normal life well into old age given a good diet, exercise and an appropriate DMT. An old guy like me, whose MS is probably more or less dormant now anyway, only has diet and exercise to rely on as a positive therapy, but there are some potential neuro-regenerative possibilities on the horizon.

[ActiveMSers]

Niko, here you go. 50 RRMS w/o drug compared with 141 treated, all with early drugs (interferon and Copaxone). There are many studies that suggest a possible connection between atrophy prevention and DMTs, but as usual there are others that say they may not influence it that much. Sadly brain atrophy in MSers compared to regular folks is a hallmark of the disease, starts extremely early on, and is a serious side effect. Anything we can do to slow it down is important.

I recently posted a 4-part series on cognition that also addressed the lack of success with supplements in cognition (atrophy was not studied I believe).

http://activemsers.wssnoc.net/showth...hlight=biloba:

Effect of disease-modifying drugs on cortical lesions and atrophy in relapsing–remitting multiple sclerosis

M Calabrese, V Bernardi, M Atzori, I Mattisi, A Favaretto, F Rinaldi, P Perini and P Gallo

Abstract

Objective: To measure the effects of disease-modifying drugs (DMDs) on the development of cortical lesions (CL) and cortical atrophy in patients with relapsing–remitting multiple sclerosis (RRMS).

Methods: RRMS patients (n¼165) were randomized to subcutaneous (sc) interferon (IFN) beta-1a (44mcg three times weekly), intramuscular (im) IFN beta-1a (30mcg weekly) or glatiramer acetate (GA; 20mg daily). The reference population comprised 50 untreated patients. Clinical and MRI examinations were performed at baseline, 12 months and 24 months.

Results: One hundred and forty-one treated patients completed the study. After 12 months, 37/50 (74%) of untreated patients developed 1 new CL (mean 1.6), compared with 30/47 (64%) of im IFN beta-1a-treated patients (mean 1.2, p¼0.021), 24/48 (50%) of GA-treated patients (mean 0.8, p¼0.001) and 12/46 (26%) of sc IFN beta-1a-treated patients (mean 0.4, p<0.001). After 24 months, 1 new CL was observed in 41/50 (82%) of untreated (mean 3.0), 34/47 (72%) of im IFN beta-1a-treated (mean 1.6, p<0.001), 30/48 (62%) of GA-treated (mean 1.3, p<0.001) and 24/46 (52%) of sc IFN beta-1a-treated patients (mean 0.8, p<0.001). Mean grey matter fraction decrease in DMD-treated patients at 24 months ranged from 0.7 to 0.8 versus 1.0 in untreated patients (p¼0.023).

Conclusions: Disease-modifying drugs significantly decreased new CL development and cortical atrophy progression compared with untreated patients, with faster and more pronounced effects seen with sc IFN beta-1a than with im IFN beta-1a or GA.

Full PDF
http://www.google.com/url?sa=t&rct=j...jPJh2fi-eWdIqw

[ActiveMSers]

This related article was released in May of 2013. Unfortunately, brain atrophy starts early, even before official diagnosis.

Clinical impact of early brain atrophy in clinically isolated syndromes

F Pérez-Miralles1,2
J Sastre-Garriga1
M Tintoré1
G Arrambide1
C Nos1
H Perkal1
J Río1
MC Edo1
A Horga1
J Castilló1
C Auger3
E Huerga3
A Rovira3
X Montalban1

1Multiple Sclerosis Center of Catalonia (Cemcat), Hospital Universitari Vall d’Hebron, Barcelona, Spain

2Department of Medicine, Universitat Autònoma de Barcelona, Spain

3Department of Radiology, Hospital Universitari Vall d’Hebron, Barcelona, Spain

Jaume Sastre-Garriga, Cemcat, Edifici Antiga Escola d’Infermeria, 2ª planta, Hospital Universitari Vall d’Hebron, Passeig de la Vall d’Hebron 119–129, Barcelona, 08035, Spain.

Abstract

Background: The impact of global and tissue-specific brain atrophy on conversion to multiple sclerosis (MS) after a clinically isolated syndrome (CIS) is not fully gauged.

Objectives: We aimed to determine the magnitude and clinical relevance of brain volume dynamics in the first year after a CIS.

Methods: We assessed 176 patients with CIS within 3 months of onset, clinically and by conventional magnetic resonance imaging (MRI) scans, at baseline and 1 year after clinical onset. We determined the percentage of brain volume change (PBVC) and the brain parenchymal (BPF), grey matter (GMF) and white matter (WMF) fractions.

Results: The mean follow-up time was 53 months (SD = 16.8): 76 patients (43%) experienced a second attack, 32 (18%) fulfilled MRI-only 2005 McDonald criteria and 68 (39%) remained as CIS. Statistically significant decreases in the volume measures tested were observed in patients with a second attack, for BPF and PBVC; in both MS groups for GMF; whereas in all groups, the WMF was unchanged. Patients with a second attack had larger PBVC decreases (− 0.65% versus + 0.059%; p < 0.001). PBVC decreases below − 0.817% independently predicted shorter times to a second attack.

Conclusions: Global brain and grey matter volume loss occurred within the first year after a CIS; brain volume loss predicted conversion to MS.