J Alzheimers Dis. 2015 Jun 25;46(3):687-693.

Clinical Benefits for Older Alzheimer’s Disease Patients: Okayama Late Dementia Study (OLDS).

Matsuzono K, Yamashita T, Ohta Y, Hishikawa N, Sato K, Kono S, Deguchi K, Nakano Y, Abe K.




There are few reports on the effects of anti-Alzheimer’s disease (AD) drugs on older AD patients, and possible differences based on gender in a real world setting.


“Okayama Late Dementia Study (OLDS)” is a retrospective clinical cohort study focusing on older AD patients (n = 373; age≥75 years) treated with monotherapy donepezil (n = 55), galantamine (n = 222), rivastigmine (n = 63), or memantine (n = 33). The patients were evaluated as an entire group and separated by gender, using seven batteries for dementia assessment at baseline and at 3, 6, and 12 months of drug therapy.


All four drugs preserved cognitive and affective functions until 12 months, except for Frontal Assessment Battery (FAB) with memantine ( *p <  0.05 versus baseline). Donepezil monotherapy significantly improved Hasegawa Dementia Rating Scale-Revised (HDS-R) at 3 months ( *p <  0.05), and memantine (3 and 6 months, *p <  0.05) and rivastigmine (3 months, **p <  0.01) improved Abe’s Behavior and Psychological Symptom of Dementia Score (ABS), respectively. Activities of daily living (ADL) became significantly worse with galantamine at 12 months ( *p <  0.05). Male Mini-Mental State Examination scores became worse at 12 months with donepezil ( *p <  0.05), as did female Geriatric Depression Scale scores at 6 months ( *p <  0.05). Male HDS-R and ABS scores were preserved in the galantamine group until 12 months. Female ABS scores with memantine improved at 6 months ( *p <  0.05), while male ADL scores became worse with rivastigmine at 12 months ( *p <  0.05).


OLDS revealed that anti-AD drugs were effective even for older AD patients, and the clinical benefits of each drug showed a small difference with regard to gender.


Activities of daily living; Alzheimer’s disease; affective function; cognitive function; gender difference; late elder patients

PMID: 26402513



Alzheimer’s disease (AD) is the most popular disease causing dementia in the world. There are some clinical differences between early onset AD and late onset AD patients. In addition, there are significant gender differences in the AD prevalence, ε4 allele, and so on. Some scientists showed estrogen associate AD and estrogen was tried for the anti-AD drug in the clinical studies at past (Almost all studies have failed to our sorrow) (1). There are 4 available anti-AD drugs in 2015 and a lot of studies have evaluated the effect differences between drugs. Clinical physicians choose the anti-AD drug for treatment according to these results. However, there are few reports which evaluate these 4 drugs effects based on age and gender. Thus, we performed the study called “Okayama Late Dementia Study” nicknamed “OLDS”.


There are 2 major purposes of “OLDS”, which are

  •   To evaluate the effect of the 4 AD drugs on older AD patients.
  •   To examine gender differences for each AD drug.


Figure 1

Our study design is showing in Figure 1. We have studies 373 AD patients for 12 months separated with drugs and gender. AD patients were evaluated with 7 batteries: Mini-Mental State Examination Examination (MMSE), Hasegawa Dementia Rating Scale-Revised (HDS-R), Frontal Assessment Battery (FAB), Geriatric Depression Scale (GDS), Apathy Score (AS), Abe’s Behavior and Psychological Symptom of Dementia Score (ABS) (2), and Alzheimer’s Disease Cooperative Study Group-Activity of Daily Living (ADCS-ADL).


Figure 2


Results are showing in Figure 2 (above) and Figure3 (below) and summarizing as following:

  • Anti-AD drugs were effective even for older AD patients.
  • The anti-AD drugs effect may be shorter compared with younger AD patients of previous reports.
  • There are significant gender differences in effectiveness of anti-AD drugs.
  • Donepezil was better for female cognitive functions. Galantamine was better for male cognitive and affective functions. Rivastigmine was better for female ADL. Memantine was better for female affective functions.


Figure 3


Clearing the reason of gender differences in effectiveness of anti-AD drugs is our future challenge. We hope our “OLDS” data help clinical physicians for anti-AD drugs choice and provide better treatment for AD patients.



  1. Shumaker SA, Legault C, Rapp SR, Thal L, Wallace RB, Ockene JK, Hendrix SL, Jones BN 3rd, Assaf AR, Jackson RD, Kotchen JM, Wassertheil-Smoller S,Wactawski-Wende J; WHIMS Investigators 2003 Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: the Women’s Health Initiative Memory Study: a randomized controlled trial. JAMA 289: 2651-2652.
  2. Abe K, Yamashita T, Hishikawa N, Ohta Y, Deguchi K, Sato K, Matsuzono K, Nakano Y, Ikeda Y, Wakutani Y, Takao Y 2015 A new simple score (ABS) for assessing behavioral and psychological symptoms of dementia. J Neurol Sci 350: 14-17.



This work was partly supported by a Grant-in-Aid for Scientific Research (B) 2529320216 from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and by Grants-in-Aid from the Research Committee of CNS Degenerative Diseases (K. Nakashima), and grants (Mizusawa H, Nishizawa M, Sasaki H, and Sobue G) from the Ministry of Health, Labour and Welfare of Japan.



Koji Abe, MD, PhD


Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama, Japan.



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