Alzheimer’s Disease – Strong Evidence for Halting this Disease

Decreased intra- and inter-network connectivity in a patient with Alzheimer prior to treatment

Alzheimer’s disease (AD) is a neurodegenerative condition and the most devastating among the dementing illnesses. The etiology of AD involves extracellular β-amyloid (amyloid precursor protein, APP) deposits.

The AD hypothesis is based on the amyloid cascade and tau hyperphosphorylation. The tau hypothesis states that abnormal phosphorylation of tau results in the transformation of normal adult tau into PHF-tau (paired helical filament) and neurofibrillary tangles NFTs.

Vascular hypothesis for AD indicates that with age vascular risk factors increase creating a Critically Attained Threshold of

Normal intra and inter-network connectivity in healthy volunteers

Cerebral Hypoperfusion (CATCH) leading to cellular pathology involving protein synthesis, development of plaques, inflammatory response, and synaptic damage that evolves into AD1,2.

To date, pharmacological treatments have not obtained favorable results and that has created room for non-pharmacological interventions to be used for this disease.

Transcranial magnetic stimulation (TMS) can induce changes in brain activity and cause long-term modifications in impaired neural networks. Such capabilities of TMS hold many promises for clinical intervention.

Standard TMS can cause changes in cortical excitability, increases brain plasticity, and facilitates the recovery by the reorganization of impaired neural networks responsible for cognitive impairment3-8.

However, standard TMS does not offer individualized targeting capabilities that can be rectified by using advanced MRI techniques.

Treating Alzheimer’s with fMRI

A large body of recent research shows that AD is due to an impairment of the connectivity of the default mode network (DMN) compared to healthy individuals.

In our clinic, we use fMRI to map the entire brain networks and then run a special analysis for each patient to find the right target for TMS treatment with the largest outcome for strengthening the DMN.

As fMRI has been emerging as a technique to produce biomarker-surrogate for neurodegenerative diseases, it can identify the presence of AD and it allows for tracking progression, severity, guide TMS treatment, and offer an assessment of treatment effects.

More and more evidence is being reported every day that interventions in neurodegenerative disorders must be applied in very early or even pre-symptomatic phases of AD.

As such, the use of a sensitive technique like fMRI for monitoring disease progression based on quantitative measures combined with clinical features offers a reliable and easy-to-track biomarker in this field.

We offer fMRI guided TMS treatment of AD by using measures of quality. High-resolution fMRI and neuro-navigation-based TMS with their combined objectivity, reliability, and validity enable us to use them to construct biomarkers to guide our treatment of AD patients. This is particularly important, as our biomarkers are measurable non-invasively and do not put challenging demands on the patient (e.g., following demanding cognitive tasks).

These powerful features of fMRI have enabled us to rectify many of the shortcomings of standard TMS and turn their combination into an indispensable technique for the treatment of AD.



1. Liao X, Li G, Wang A, Liu T, Feng S, Guo Z, Tang Q, Jin Y, Xing G, McClure MA, Chen H, He B, Liu H, Mu Q. Repetitive Transcranial Magnetic Stimulation as an Alternative Therapy for Cognitive Impairment in Alzheimer’s Disease: A Meta-Analysis. J Alzheimers Dis. 2015; 48(2):463-72.

2. Hsu WY, Ku Y, Zanto TP, Gazzaley A. Effects of noninvasive brain stimulation on cognitive function in healthy aging and Alzheimer’s disease: a systematic review and meta-analysis. Neurobiol Aging. 2015 Aug; 36(8):2348-59.

3. Cotelli M, Manenti R, Zanetti O, Miniussi C. Non-pharmacological intervention for memory decline. Front Hum Neurosci. 2012 Mar; 6:46.

4. Cotelli M, Calabria M, Manenti R, Rosini S, Zanetti O, Cappa SF, Miniussi C. Improved language performance in Alzheimer’s disease following brain stimulation. J Neurol Neurosurg Psychiatry. 2011 Jul; 82(7):794-7.

5. Nardone R, Tezzon F, Höller Y, Golaszewski S, Trinka E, Brigo F. Transcranial magnetic stimulation (TMS)/repetitive TMS in mild cognitive impairment and Alzheimer’s disease. Acta Neurol Scand. 2014 Jun;129(6):351-66.

6. Ahmed MA, Darwish ES, Khedr EM, El Serogy YM, Ali AM. Effects of low versus high frequencies of repetitive transcranial magnetic stimulation on cognitive function and cortical excitability in Alzheimer’s dementia. J Neurol. 2012 Jan; 259(1):83-92.

7. Haffen E, Chopard G, Pretalli JB, Magnin E, Nicolier M, Monnin J, Galmiche J, Rumbach L, Pazart L, Sechter D, Vandel P. A case report of daily left prefrontal repetitive transcranial magnetic stimulation (rTMS) as an adjunctive treatment for Alzheimer disease. Brain Stimul. 2012 Jul; 5(3):264-266.

8. Hohenfeld C, Werner CJ, Reetz K. Resting-state connectivity in neurodegenerative disorders: Is there potential for an imaging biomarker?. Neuroimage Clin. 2018 Mar;18:849–870.

Meet Neurotherapeutix NYC

Neurotherapeutix is the leading clinic for functional imaging guided transcranial magnetic stimulation (TMS), a safe, innovative, and non-invasive methodology for treating a wide range of acute and chronic mental disorders and brain injuries. Our advanced fMRI technology allows us to map the brain for the... Learn More »